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+The goal of this systematic review was to examine the effects of interferon treatment for interferon naive (previously untreated) patients with chronic hepatitis C. This review confirmed the efficacy of interferon on surrogate outcomes as well as a favourable effect of higher treatment doses and prolonged durations. However, these effects were associated with more adverse events. Compared with non-cirrhotic patients, cirrhotic patients respond similarly, but the efficacy of interferon in patients with normal liver biochemistry is not substantiated by the data. Although interferon monotherapy is no longer considered the standard therapy for chronic hepatitis C, this review defines the optimal dose and duration of interferon monotherapy, which may be useful for patients who cannot tolerate combination therapy including interferon and ribavirin, the most effective therapy currently available.
+We assessed the benefits and harms of bicarbonate-buffered solutions and lactate-buffered solutions by analysing results from four randomised controlled studies that together involved 171 participants. The evidence was flawed by study design and reporting problems, and the small number of people in the studies. Based on limited evidence from one study (117 participants), we found that people treated with bicarbonate-buffered solutions may experience fewer heart and blood circulation problems and high blood pressure events. The studies did not include enough evidence to make recommendations about the use of these solutions.
+Overall, the studies we found do not give a clear answer on whether probiotics reduce the occurrence or severity of diarrhoea, improve quality of life, or reduce the need for other medication. However, an analysis of only well-performed studies demonstrated a beneficial effect for some outcomes. With regard to prevention of diarrhoea compared with placebo in participants treated with radiotherapy with or without chemotherapy, we are not able to conclude whether use of probiotics would be beneficial based on the five relevant studies. For prevention of diarrhoea due to chemotherapy alone, three studies suggested that use of probiotics may not reduce diarrhoea, and one study reported use of less rescue medication for diarrhoea. Three studies that compared probiotics with another agent for preventing diarrhoea in patients treated with radiotherapy with or without chemotherapy found beneficial effects of probiotics for the occurrence and severity of diarrhoea and the need for rescue medication. With respect to treatment of diarrhoea due to radiotherapy, we found only one study that did not demonstrate a clear effect of probiotics compared with placebo. No study reported serious adverse events nor deaths related to diarrhoea. The quality (certainty) of the evidence in prevention studies was low to very low. For the only study that assessed the effects of probiotics on treatment for diarrhoea, the certainty of the evidence was moderate. Evidence supporting the effects of probiotics in preventing or treating diarrhoea related to cancer treatment is insufficient. However, probiotics appear to be safe, as no studies have found severe side effects.
+We conducted a Cochrane systematic review of 12 randomised controlled trials that examined the effectiveness of family-based universal programs for the prevention of alcohol misuse in young people. In family settings, universal prevention typically takes the form of supporting the development of parenting skills including parental support, nurturing behaviours, establishing clear boundaries or rules, and parental monitoring. Social and peer resistance skills, the development of behavioural norms and positive peer affiliations can also be addressed with a universal family-based preventive program. Most of the studies included in this review reported positive effects of family-based universal programs for the prevention of alcohol misuse in young people. Two studies, each with a large sample size, reported no effects. In conclusion, in this Cochrane systematic review we found that that the effects of family-based prevention interventions are small but generally consistent and also persistent into the medium- to longer-term.
+We included 24 studies with 10,056 women in the review, and 20 studies involving 9789 women contributed data to the analyses. Most studies took place in high-income countries including the USA, Canada, UK and Australia. Peer counselling, lactation consultation and formal BF education during pregnancy do not appear to improve uptake of BF or duration. However, some larger trials in different settings (one in Nigeria and one in Singapore) had some evidence that education may help. We are still unsure if antenatal BF education is able to help women; at present, there is no good evidence from randomised controlled trials to suggest these efforts to educate pregnant women translate into more and longer BF. Women who receive standard care before birth tend to choose BF at about the same rate as women who have extra BF education. We are confident in the results of studies measuring women's uptake of BF at birth and BF at six months; education does not appear to impact these decisions. We have some doubts about the impact of education on exclusive BF at three and six months; education does not seem to help women, but future studies may change our understanding. Future studies are likely to change our understanding of the impact of BF education during pregnancy on BF at three months. Most of the studies in this review took place in higher income countries, so we are not confident that our conclusions are relevant in other settings.
+This review found that there are three trials that have compared these methods. It seems that the initial operative plan is changed more often in patients who have conventional laparoscopic surgery compared to hand assisted surgery - they more often end up with a hand assisted or open approach (it is most commonly to the hand assisted approach). There is a need for larger trials that explain the manner in which the trials were conducted. An economic analysis is also needed since the hand assist device is expensive and longer follow up of patients is needed.
+A comprehensive package comprising career guidance, mentoring, and academic, social and financial support may result in increased graduation rates among health professional students at risk of dropping out of study. Further research could focus on determining the magnitude of student drop-out rates in health professional training institutions, identifying the students at risk of dropping out, and determining the applicability of western-based innovations in low and middle-income countries. Evaluation of ongoing and planned interventions in pre-licensure education of health professionals is important.
+We found four studies involving 234 women who had been in preterm labour and had their contractions stopped. We found no evidence of terbutaline maintenance therapy offering any advantages over saline placebo pump or oral terbutaline maintenance therapy in reducing adverse neonatal outcomes by prolonging pregnancy among women with arrested preterm labour. The review found there are not enough large trials to show whether terbutaline pump maintenance therapy is safe or effective.
+Despite extensive searching, we identified only seven studies for inclusion. Our assessment of the quality and strength of evidence from these studies is low. This review shows that only a handful of medication safety strategies are studied in robust study designs. When the vulnerability of paediatric patients in hospital is considered, more research of high quality should be included on every research agenda.
+The evidence obtained is current to September 2013. We re-ran the search in February 2015 and we will deal with the study awaiting classification when we update the review. We included 10 studies involving 813 participants. The included studies compared propofol with five other alternative drugs used to sedate people in the ED. We could not pool the results of the 10 studies because no two studies compared the same drug options. We found very low quality evidence for the effects of propofol and the other drugs used for sedating people in the ED in terms of complications (side effects, including pain at the injection site) and participant satisfaction. In one study comparing a drug combination of propofol and fentanyl (a painkiller) with midazolam and ketamine (a drug which acts as both a painkiller and a sedative), delayed adverse reactions (nightmares and behavioural change) were noted in 10% of the ketamine/midazolam group and none in the propofol/fentanyl group. The quality of the evidence was overall very low.
+We found 13 randomised controlled trials with parallel groups, comparing aspirin with placebo or no treatment in a total of 2653 women undergoing ART. Studies were conducted in the USA and a variety of countries in Europe and Asia. One of the included trials was partly funded by a pharmaceutical company relevant to the intervention. In most of the studies, groups were comparable and the mean age of participants in both groups was 32 years. An identical dose of the intervention was administered in most of the studies and most reported a similar timing of the initiation of aspirin intake. The duration of trial varied across the studies, but was sufficient to provide data on the reported outcomes as respectively investigated by each group. The evidence is current to 9 May 2016. There was no evidence of a difference between the groups in rates of live birth, clinical pregnancy, ectopic pregnancy, multiple pregnancy, miscarriage or vaginal bleeding. The number of studies was limited and the quality of the evidence ranged from very low to moderate, while data on complication rates, either during the IVF/ICSI procedure or during pregnancy and childbirth were either very limited or missing. At this second update we were not able to add new data from additional studies, as we found no new RCTs reporting on these outcomes in the prespecified comparisons. Based on the available evidence, we reached the same conclusion as the initial version of the review: no single outcome measure demonstrated a benefit with the use of aspirin. Currently, there is no evidence to support the use of aspirin treatment in order to improve pregnancy rates for a general IVF population. The evidence was of moderate quality for live birth and of very low to moderate quality for other outcomes. The main limitations of the evidence were poor reporting of study methods, publication bias and lack of studies investigating the desired outcomes.
+We searched for evidence up to 30 June 2016. This review includes 15 studies involving 3490 women (3 studies involving 152 women were added for this update). Women with a stitch are less likely to have a baby who is born too early. Babies whose mothers had a stitch are also less likely to die during the first week of life. It is not clear whether a cervical stitch can prevent stillbirth or improve the baby's health once born. Inserting a stitch helps pregnant women who are at high risk avoid early births compared to no stitch. Inserting a stitch may also improve a baby's chance for survival. We found too few clinical trials to understand whether cervical stitch is more effective than other treatments for preventing early births, such as progesterone (a hormone drug used to prevent early birth). We found too few data to understand if it is better to have a stitch inserted early in pregnancy (based on the mother's previous history) or to wait to perform an ultrasound scan later in pregnancy to see if the cervix has become shortened.
+The review included eight randomised controlled trials published up to August 2012, involving 6615 participants. Four of these trials were newly included in this update. Low to moderate quality evidence included in this review shows that mobile phone text messaging reminders increase attendance at healthcare appointments compared to no reminders and postal reminders, and have the same impact on attendance as phone call reminders. Two studies reported that the costs per attendance of mobile phone text message reminders are less than phone call reminders. One study reported generally that there were no adverse effects during the study period; none of the studies reported in detail on specific adverse events such as loss of privacy, data misinterpretation, or message delivery failure. The studies included in the review did not report on health outcomes or people's perceptions of safety related to receiving reminders by text message. Further randomised trials are needed to assess the effects of mobile phone messaging reminders for attendance at healthcare appointments.
+We performed a comprehensive literature search of the standard medical databases (from database inception to 17 April 2018) in consultation with the Cochrane Gynaecology and Fertility Group Information Specialist, for all randomised controlled trials (studies in which participants are assigned to a treatment group using a random method) investigating the efficiency of IVM compared to conventional ART in subfertile women with PCOS. We searched for and included studies irrespective of language and country of origin. Two review authors independently selected and evaluated studies, extracted data, and attempted to contact the authors of studies for which data were missing. We found two studies (71 women), published as abstracts in international conferences, and six ongoing trials that met our inclusion requirements. Though promising data on the IVM technique have been published, unfortunately there is still no evidence concerning our primary outcomes of live-birth and miscarriage rates from properly conducted randomised controlled trials upon which to base any practice recommendations regarding IVM before ART for women with PCOS. Of the secondary outcomes specified in this review, very low-quality evidence showed that clinical pregnancy was higher when IVM was compared to conventional ART, whereas the incidence of ovarian hyperstimulation syndrome was zero in both studies in both groups. We are awaiting the results of six ongoing trials and eagerly anticipate further evidence from good-quality trials in the field. The quality of the evidence was very low for all outcomes.
+We included four studies involving 365 women. High or low feedback of prenatal ultrasound to reduce women's state of anxiety is not supported by evidence from the three randomised controlled trials, involving 346 pregnant women, that looked at this outcome (low-quality evidence). Two trials with a total of 148 women reported on the women's views on the level of feedback. The women in the high feedback groups were not clearly more likely to choose very positive adjectives to describe their feelings after the scan. One trial with 129 participants reported that women who had high feedback during ultrasound were more likely to stop smoking and avoid alcohol during pregnancy. The trials were reported on between 1985 and 1996.
+However, this update the review first published in 2002 (D'Angelo 2002) found there is not enough evidence to show whether using frozen embryos and or intravenous albumin infusion (artificial fluid to increase the woman's blood volume) can reduce OHSS in women who are at high risk. More research is needed on effects on pregnancy rates.
+We included eight randomised clinical trials with 555 participants. All trials compared acupuncture versus no intervention. Seven trials included participants with chronic hepatitis B. One trial included chronic hepatitis B participants with tuberculosis and ascites. These trials assessed heterogeneous acupuncture interventions (i.e. manual needle acupuncture, acupoint herbal patching, acupoint injection, and moxibustion). Acupoint is a specifically chosen site for acupuncture manipulation. All trials used heterogeneous co-interventions applied equally in the compared groups. Three of the eight included randomised clinical trials received academic funding. None of the remaining five trials reported information on support or funding. None of the eight included trials reported data on clinically important outcomes such as all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, or hepatitis B-related morbidity. We are uncertain whether acupuncture compared with no intervention has a beneficial or harmful effect regarding adverse events considered not to be serious. Acupuncture compared with no intervention seems to reduce the proportion of people with detectable hepatitis B virus (HBV) DNA (a non-validated surrogate outcome; only one trial). We are uncertain whether acupuncture compared with no intervention has an effect on the proportion of people with detectable HBeAg (a non-validated surrogate outcome; only two trials). Caution is needed in interpreting these findings as data are provided by only one or a few trials at high risk of bias, and these surrogate outcomes have not yet been proven relevant for people with chronic hepatitis B. We are uncertain whether acupuncture compared with no intervention has an effect on the remaining separately reported adverse events considered not to be serious. We could not use data from 79 other studies, of possible interest to our review, because study authors provided highly insufficient information on their study design and methods. Accordingly, we need more information from randomised clinical trials before benefits or harms of acupuncture for chronic hepatitis B can be determined. Certainty of evidence means 'the extent of one's confidence that review results are correct in supporting or rejecting a finding'. The certainty of evidence on the use of acupuncture in people with chronic hepatitis B virus infection in terms of its beneficial or harmful effects on death, health-related quality of life, risk of dying due to HBV infection, and serious adverse events cannot be determined, as data on these outcomes were lacking. The certainty of evidence on acupuncture, when compared with no intervention, in terms of adverse events considered not to be serious, the proportion of people with detectable HBV DNA, and the proportion of people with detectable HBeAg, is very low. Whether the last two outcomes are relevant to the well-being of people with chronic hepatitis B is still not scientifically proven. The very low certainty of the evidence is due to insufficient data ensuing from one, two, or very few trials with insufficient reporting.
+Ciliary neurotrophic factor treatment did not show any significant effect on the progression of amyotrophic lateral sclerosis and side effects were observed at high concentrations.The review found only two eligible trials with a total of 1300 participants; the risk of bias was low for one trial but was unclear for the other trial; they did not show any significant effect of ciliary neurotrophic factor on progression of ALS or MND in man. On the other hand, several adverse effects were observed after treatment with ciliary neurotrophic factor. An updated search was performed in April 2011, but no new studies were found.
+We selected 14 studies with a total of 2715 men and non-pregnant women with CT infection, who had been treated with any antibiotic recommended by clinical guidelines (2147 (79.08%) men and 568 (20.92%) women). Women showed no symptoms or had uterine cervicitis, and men had non-gonococcal urethritis (an inflammation of the urethra not caused by gonorrhoeal infection). All of the participants had a positive test for CT. The studies lasted from 7 to 84 days after the end of treatment, with an average of 28 days. Most of the studies took place in sexually transmitted disease clinics in the USA. Studies compared the antibiotics doxycycline with azithromycin, and doxycycline with ofloxacin. One study reported funding from academic grants, another four studies declared having received sponsorship or grants from pharmaceutical companies. The other studies declared that they were self-funded or did not mention funding at all. We developed meta-analysis (a way of combining the results of studies), for two comparisons: azithromycin 1 g single dose versus doxycycline 100 mg twice a day for seven days, and doxycycline 100 mg twice a day for seven days versus ofloxacin 300 mg to 400 mg once daily or twice daily for seven days. We found that microbiological failure was less likely in men treated with doxycycline than men given azithromycin, and there were fewer adverse events (side effects) in men and women with azithromycin. There were no differences in clinical failure for women or men in doxycycline versus azithromycin nor in doxycycline versus ofloxacin. This means that with current available evidence, doxycycline would be the first option for treatment in men with urethritis. For non-pregnant women with CT infections there are no advantages with any of the included antibiotics. However, clinicians could consider single-dose azithromycin as an option, because it caused fewer adverse events. The included studies used poor methods that could mean that their results were biased (incorrectly favouring one drug instead of the other). This means we thought that the evidence they provided for microbiological failure in men, and for adverse events in men and women when azithromycin was compared with doxycycline was moderate quality, and for all the outcomes when doxycycline was compared with ofloxacin, we thought it was very low quality.
+The evidence included in this review is current as of February 2016 and is based on 17 reports representing 11 unique studies in 297,994 high school students. The studies examined a range of changes to school time (for example, moving the start time fifteen minutes later, moving the start time an hour later) and a range of intervention durations (one as short as two weeks, others lasting a year), but all focused on natural settings (students already in schools, rather than in a laboratory setting). Although 5 of the 11 studies were funded, the funding sources were academic and research institutions, rather than agencies with a commercial interest in program evaluation results. Because of the limited and very low-quality evidence, we could not determine the effects of later school start times with any confidence. We found that later school start times may provide academic benefits, but results of four studies provided mixed findings. Later school starts were associated with an increase in school-night sleep for students based on the synthesis of two studies, and evidence from six other studies also supported the relationship between later school starts and increased sleep duration. One study reported that students in later starting schools reported fewer depressive symptoms than their peers in earlier starting schools. Different studies reported mixed findings regarding the association between later school start times and increased attendance and student alertness. These interventions may also have potential adverse effects on logistics, as the qualitative portions of one study reported less interaction between parents and children, and another reported staffing and scheduling difficulties. Again, because of the limited and very low-quality evidence, we cannot draw any firm conclusions about the adverse effects of later school start times. The quality of this evidence was very low, and thus we cannot assume the findings reflect the true beneficial or adverse effects of later school start times.
+We identified 12 eligible trials enrolling a total of 746 preterm infants in searches updated to February 2016. An overall analysis suggests that non-nutritive sucking reduces the time infants need to transition from tube to full oral feeding, and from start of oral feeding to full oral feeding. It also reduces the length of hospital stay. Non-nutritive sucking did not demonstrate a positive effect on weight gain. Participants numbers in these studies were small, and we judged the quality of the evidence on outcomes assessed to be low or very low. Large well-designed randomised controlled trials are necessary for further evaluating the effectiveness and safety of non-nutritive sucking for increasing physiologic stability and nutrition in preterm infants.
+The evidence on which this review is based was up to date as of 22 October 2013. We searched scientific databases and found seven studies to include in this review comparing composite resin fillings with amalgam fillings and we included two of these studies in the main analysis. There were 3265 composite fillings and 1935 amalgam fillings but is unclear how many children these were in. The exact age of participants was also unclear in some studies; however, both children and adults with permanent teeth at the back of the mouth that required fillings were included. Study centers were located in the UK, USA, Portugal, Sweden, The Netherlands, Belgium, and Germany. The main result including only two studies in 921 children suggests that amalgam fillings had lower failure rates than tooth-colored (composite resin) fillings used to fill holes caused by decay in permanent teeth at the back of the mouth. Further tooth decay (secondary caries) also occurred less frequently next to or under amalgam fillings compared with composite resin fillings. There was no evidence of a difference in the breaking of the two types of fillings. The other five studies only reported the rate of failure of the fillings and the amount of further tooth decay occurring next to or under the fillings (secondary caries) and the results supported those of the two studies above. The results suggest that tooth-colored (composite resin) fillings are almost twice as likely to fail compared with amalgam fillings when used for filling permanent teeth at the back of the mouth. The quality of the evidence was low to moderate. Because there was an obvious difference in the color of the fillings, it was not possible to do the comparisons 'blind' so there was, therefore, a high risk of bias.
+The authors of this review undertook a systematic review of the potential benefits and safety of TCHP in patients with stable angina. Three randomised controlled studies with a total of 216 patients were identified. Only one small trial was able to detect benefits of using TCHP compared with nitrates in improving angina symptoms. The remaining two trials were inconclusive. Due to the very small number of included studies and participants in the studies, TCHP should be used with caution. We recommend that larger-scale high quality randomised controlled trials of TCHP are required to strengthen the evidence for the efficacy and safety of certain TCHP in treating angina.
+Seven randomised controlled trials involving 1839 patients with clinically confirmed DVT compared home (LMWH) versus hospital (unfractionated heparin, or LMWH in one trial) treatment. Trials had limitations, including high exclusion rates and designs that did not take into account short hospital stays for any of the people treated at home to allow fair comparison of heparin in hospital with LMWH at home. Trials showed that patients treated at home with LMWH had less recurrence of VTE than hospital-treated patients. The review showed no clear differences between treatment groups for major bleeding, minor bleeding, or death. No study reported venous gangrene. We could not pool information on patient satisfaction and quality of life, as studies had different ways of reporting these, but two of the three studies reporting on quality of life provided evidence that home treatment led to greater improvement in quality of life compared with in-patient treatment, at some point during follow-up. The third study reported that a large number of participants chose to switch from in-patient care to home-based care for social and personal reasons, indicating that home treatment was better accepted than in-patient treatment. Studies that looked at cost found that cost of home management was lower per incident of treatment. Overall, the quality of evidence of the available data was low to very low owing to risk of bias, indirectness, and differences in measuring and reporting of outcomes. Risk of bias is a concern, as many of the included studies did not fully explain how they randomised and allocated participants to treatments, and blinding techniques described were not clear. Full blinding would be difficult if not impossible for these types of treatments (home vs hospital), but some techniques could be put in place such as using the same treatment medications or blinding those who measure outcomes. Another concern of reviewers was that in some studies, participants randomised to home treatment actually ended up being treated in hospital but remained in their assigned treatment for the analysis (this is known as indirectness). This makes it hard to determine whether trial results actually can be used to answer the question of whether home versus hospital treatment for DVT is superior. A further concern regarding a few of outcomes is variation in the way outcomes were measured and reported.
+In December 2016 we searched for randomised controlled trials involving participants of any age or sex, whose pilonidal sinus had been treated with fibrin glue, either on its own or with surgery. We found four studies that included 253 participants, the majority of whom were male. Fibrin glue on its own was compared with surgery in one study. In three studies fibrin glue was applied during surgery and compared with surgery on its own. There were problems with the design and conduct of all four studies which mean that their results are very uncertain. It is not known whether fibrin glue on its own affects time to healing and adverse events compared with a type of surgery (Bascom's procedure). Fibrin glue may result in less pain on the first day after the procedure compared with Bascom's procedure. When fibrin glue is used alongside a type of surgery called the Limberg flap it may reduce the healing time by approximately 14 days compared with the surgery on its own, however this finding is highly uncertain as the evidence is very low-quality. It is uncertain whether using the fibrin glue alongside the Limberg flap affects the incidence of a complication called seroma (a collection of fluid) but it may reduce postoperative pain (this evidence is low-quality and therefore quite uncertain) and may reduce time to return to normal activities (low-quality evidence) and length of hospital stay (this was very low-quality evidence and therefore very uncertain). One study evaluated the effect of adding fibrin glue to a type of surgery called the Karydakis flap. It is not clear from this study whether using the glue affects time to healing or the incidence of seroma. Using the fibrin glue with the Karydakis flap may reduce length of hospital stay compared with surgery alone but again this is low-quality evidence. The quality of evidence for all outcomes was low or very low, mainly due to problems with the ways the studies were conducted and also the uncertainty in the results because of the small numbers of participants in the studies. This means we cannot be confident of the effects of fibrin glue on any of these outcomes and more, better quality and larger studies are required. This plain language summary is up to date as of December 2016.
+We searched the medical literature in July 2018 and found one relevant clinical trial. This trial included 1355 women who had previously had pre-eclampsia, who lived in Argentina, South Africa, and Zimbabwe. The trial compared pregnant women who had daily calcium with women who had placebo (a dummy tablet) until 20 weeks of pregnancy, when all women switched to having daily calcium until birth. We had some concerns about the evidence from this trial, because nearly a quarter of the women who were enrolled were lost to follow-up, and we do not know whether they went on to become pregnant. Overall, while the results suggested that some women may benefit from calcium supplements, the findings included the possibility that the calcium didn't make a difference. Calcium may have helped some pregnant women avoid either losing the pregnancy or developing blood pressure problems, but we need more studies to be really confident that this effect was due to calcium. Calcium may have made little or no difference to whether pregnant women had other serious health conditions during pregnancy, such as: maternal admission to intensive care, blood pressure problems (pre-eclampsia, severe pre-eclampsia, eclampsia), placental separation from the uterus (placental abruption), or death. For babies, calcium may have had little or no impact on whether they were of low birthweight, of poor condition at birth, or required intensive care. The results did not clearly indicate the impact of calcium on whether babies died either before or after the birth, or needed to be admitted to neonatal intensive care for more than 24 hours. We need more research to decide whether or not calcium before pregnancy or during early pregnancy helps women avoid high blood-pressure and other related problems. Further research is needed to confirm whether initiating calcium supplementation pre- or in early pregnancy is associated with a reduction in adverse pregnancy outcomes for mother and baby. Research could also address the acceptability of the intervention to women, which was not covered by this review update.
+This review included 24 studies with 3377 participants (current until April 2015). Seventeen studies compared pentoxifylline with placebo, and the remaining studies compared pentoxifylline with flunarizine (one study), aspirin (one study), Gingko biloba extract (one study), nylidrin hydrochloride (one study), prostaglandin E1 (two studies) and buflomedil and nifedipine (one study). Large differences between included studies in how investigators measured and reported study findings made it impossible to combine results. Most of the included studies suggested mild to moderate improvement in pain-free walking distance and total walking distance for pentoxifylline over placebo (and other treatments, which included Gingko biloba, buflomedil, iloprost, nylidrin, aspirin and prostaglandin E1). The statistical significance of findings from individual trials was unclear, and researchers observed large variability between studies in the effects of pentoxifylline. The most commonly reported side effects were gastrointestinal symptoms, mainly nausea, and the drug was well tolerated. The quality of included studies was generally low, and very large variability between studies was noted in reported findings including duration of trials, doses of pentoxifylline and distances participants could walk at the start of trials. Most included studies did not report on randomisation techniques or how treatment allocation was concealed, did not provide adequate information to permit judgement of selective reporting and did not report blinding of outcome assessors. Given all these factors, the role of pentoxifylline in intermittent claudication remains uncertain, although this medication was generally well tolerated by participants.
+Many topical treatments (applied directly to the inside of the mouth) such as sprays, lozenges, mouthrinses, gels, oils, chewing gum or toothpastes have been evaluated in this review, but there is no strong evidence that any topical treatment is effective for relieving the sensation of dry mouth. Oxygenated glycerol triester (OGT) saliva substitute spray is more effective than a water based electrolyte spray. A gel-releasing device worn in the mouth, or a mouthcare system might be effective but more research is needed. Chewing gum increases saliva production but there is no evidence that gum is better or worse than saliva substitutes. Acidic products and those containing sugar should be avoided.
+In this review, we included studies that were randomized controlled trials (RCTs) comparing progressive resistive exercise interventions with no progressive resistive exercise or another exercise or treatment modality, performed at least three times per week, and lasting at least four weeks among adults (18 years of age or older) living with HIV/AIDS. Seven studies met the inclusion criteria for this systematic review. Progressive resistive exercise or a combination of progressive resistive exercise and aerobic exercise appear to be safe and may be beneficial for adults living with HIV/AIDS. These findings are limited by the small number of studies that could be included in meta-analyses, small sample sizes and variable participant withdrawal rates among included studies. Future research would benefit from including participants at various stages of HIV infection, a greater proportion of female participants, and participants in a variety of age groups to increase the generalizability of results. Furthermore, future research would benefit from studies with larger sample sizes that conduct an "intention-to-treat" analysis (analysis of participants based on the groups to which they were originally allocated) to better understand outcomes of participants that withdraw from exercise interventions.
+To address this, 33 studies have used improvement activities directed at communities, using more than one approach in a single program. When we first looked at the available research in 2011 we observed that there was a lack of good studies which could show whether this approach was beneficial or not. Some studies claimed that community wide programs improved physical activities and other studies did not. In this update we found four new studies that were of good quality; however none of these four studies increased physical activity levels for the population. Some studies reported program level effects such as observing more people walking, however the population level of physical activity had not increased. This review found that community wide interventions are very difficult to undertake, and it appears that they usually fail to provide a measurable benefit in physical activity for a population. It is apparent that many of the interventions failed to reach a substantial portion of the community, and we speculate that some single strategies included in the combination may lack individual effectiveness.
+However, this review of trials found no strong evidence of benefit of care from specialist diabetes nurses for adolescents and adults with diabetes. Although short-term benefits may be possible, this has not been shown to result in long-term improvements. People receiving care from diabetes nurses do not appear to have improved health when compared with usual care in hospital clinics or primary care with no specialist nursing input. No data were shown on quality of life measures.
+The review found that glue is an excellent substitute for stitches, staples or tapes to close simple cuts. Glue causes less pain, is quicker and needs no follow up for removal. A slightly higher number of cuts may break open (dehisce) after being glued, compared to cuts closed with stitches, staples or tapes. Though there are a few different types of glue available, no one glue seems to be superior.
+According to GRADE, there was moderate quality evidence that participants taking medication treatment probably had less relapses/recurrences and may have lower dropouts than those taking placebo. The risk of depression returning in participants receiving a placebo (instead of antidepressant medicine) was 34%. In comparison, participants who remained on antidepressant medicines had a lower risk for recurrence of 13%. The continued treatment lasted between four months and two years. Antidepressant were as well accepted as placebo. However, as most of the included studies showed risk of bias and there were some inconsistent results between the different studies, it cannot be concluded with certainty whether continued or maintained pharmacotherapy (or both) is a convincing treatment for people with PDD. Additionally, as studies on the long-term effects of medication are lacking, recommendations on the necessary duration of medication treatment cannot be drawn. The benefits of psychological therapies or combined treatment remained unclear, due to the small number of studies. This review cannot provide clear, certain evidence regarding whether continued antidepressant medication (compared to placebo tablet) reduces the risk of depression recurring in adults with persistent depression. However, only a few studies have been done. Further studies should especially address psychological and combined long-term treatments.
+The review of trials found five studies, involving 71,458 women, comparing two fetal movement counting methods, fetal movement counting versus hormonal analysis and routine fetal movement counting compared with standard antenatal care, as defined by trial authors. In studies that compared routine counting of baby's movements in the womb with mixed or undefined counting, there was no difference in stillbirths, caesarean sections, birth weight less than 10th centile and mother-baby attachment; there was reduction in women's anxiety in the group counting the baby's movements. There was a tendency to more antenatal admissions. When counting of baby's movement was compared with hormonal analysis, there were fewer hospital visits among women who were counting and fewer babies in the hormonal analysis group had low Apgar scores, which assess the baby's condition after birth. There was no difference between the groups in terms of caesarean sections done and other outcomes. 'Perinatal death or severe morbidity' was not reported. When different types of fetal movement counting methods (once a day compared to more than once a day) were compared, women were more compliant in using the once a day counting method, citing less interruption with daily activities as one of the reasons; the incidence of caesarean section did not differ and perinatal death or severe illness was not reported. The numbers and the methodological quality of studies were insufficient to assess stillbirths accurately. Further trials are suggested, and it would be very important to assess women's anxiety and views in addition to the ability of the counting to prevent stillbirths.
+In September 2016 we searched for clinical trials where NSAIDs were used to treat chronic pain. We found seven trials (with a total of 1074 participants, aged 2 to 18 years) with chronic juvenile polyarthritis or chronic juvenile rheumatoid arthritis, which they had for more than 3 months. The studies looked at different comparisons of aspirin, celecoxib, fenoprofen, ibuprofen, indomethacin, ketoprofen, meloxicam, naproxen, and rofecoxib. No studies compared NSAIDs with placebo. We could not compare these drugs, or the pain results, as the studies all investigated different types of NSAIDs. Side effects were common, with children reporting problems with aspirin (85 out of 202 participants), fenoprofen (28 out of 49), ibuprofen (40 out of 45), indomethacin (9 out of 30), ketoprofen (9 out of 30), meloxicam (18 out of 47), naproxen (44 out of 202), and rofecoxib (47 out of 209). We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. Overall, the available evidence was low or very low quality due to a lack of data and some problems with the conduct of some studies.
+Atrial fibrillation is a common arrhythmic disease where the heart beats rapidly and irregularly. This can occur for separate brief or long episodes (paroxysmal) or it may become continuous (persistent). This review's aim was to establish whether catheter ablation was better than medical therapies to control heart rate or rhythm for paroxysmal and persistent AF. If catheter ablations were found to be better, the aim was to determine which ablation method was superior to the other. In catheter ablation, a thin tube is passed through a vein to the heart through which instruments can target the misfiring parts of the tissue that control the hearts rhythm. A total of thirty two randomised controlled trials (RCTs) were included in this review. Catheter ablation may be superior to medical treatment but the data is inconclusive in inhibiting recurrence of AF. Embolic complications were commonly caused by catheter ablation. Although these complications and death rate of catheter ablation were similar to that of medical therapies, catheter ablation may cause adverse events of radiation exploration. We were also unable to determine which catheter ablation technique was the best as most RCTs were small scale. Evidence from RCTs cannot yet support catheter ablation as the first line of treatment for paroxysmal and persistent AF.
+After a detailed search of scientific literature, we identified one trial that was eligible for inclusion. In this trial people with SCD who were diagnosed to have neuropathic pain were randomly put into groups to take either a drug named pregabalin or a placebo (no active medication) treatment. The trial was conducted in the USA and included 22 participants with SCD, with 11 people in the pregabalin group and 11 in the placebo drug group. Assessments were measured at baseline and monthly for three months. Self-reported neuropathic pain relief and quality of life scores (Short Form-36) were no different between the pregabalin and placebo groups. The outcomes of time to improvement of symptoms and changes in sleep quality were not measured in the included trial. Few unwanted effects were noted and the numbers of these were not different between participants who were given pregabalin versus those given placebo. In conclusion, the effect of pregabalin on SCD neuropathic pain was no different to placebo. We are unable to make firm conclusions regarding our objectives on the basis of a single small trial which only addressed three of our seven prespecified outcomes. Larger, well-conducted trials of different treatments for neuropathic pain in people with SCD need to be carried out. The evidence in this review was assessed as very-low quality. The single trial in this review lost more than 15% of participants to follow-up over three months. We downgraded the level of evidence due to lack of clarity in how the participants were assigned to the pregabalin or the placebo group and due to the small number of events and participants in the trial.
+Very low quality evidence showed little difference between those who had joint aspiration and those who did not in being unable to carry heavy loads or having discomfort when carrying loads using their previously injured arm at one year after injury. Very low quality evidence shows that aspiration often provides immediate pain relief and may still provide pain relief at three weeks. Neither trial reported on adverse events from the procedure, but aspiration was reported as being unsuccessful in three participants of one study. Very low quality evidence shows little effect of aspiration on being able to extend the elbow at either six weeks or one year. The reporting of adverse events was incomplete, but one trial reported the absence of three common complications of radial head fractures. Overall, there is not enough evidence to say whether aspiration gives better short-term or longer-term results than no aspiration in treating radial head fractures or how safe it is. We suggest that further research is needed to examine the use of aspiration for the initial treatment of radial head fractures.
+This review included evidence up to 19 February 2014. Five trials involving 1193 participants aged 15 years and older with acute sinusitis were included. In four trials participants received either antibiotics plus oral corticosteroids or antibiotics plus control treatment, while one trial assessed the effects of corticosteroids alone. Information on symptom relief was only available for the short term (two weeks or less) and no trial reported on relapse rates. No data for children were available. After combining trial findings, the results suggest that adults treated with oral corticosteroids plus antibiotics are more likely to have short-term symptom relief than those receiving a placebo or non-steroidal anti-inflammatory drug plus antibiotics. To benefit a single person, seven would need to receive treatment (number needed to treat to benefit). The trial assessing the effects of oral corticosteroids without antibiotics found no beneficial effects compared to placebo. Reported side effects in patients treated with oral corticosteroids were mild (nausea, vomiting, gastric complaints) and did not significantly differ from those receiving placebo. We judged the quality of the evidence for oral corticosteroids plus antibiotics to be low (further research is very likely to have an important impact on our confidence in the effect estimate and is likely to change the estimate) as the evidence is derived from four trials, including a relatively low number of participants, with a substantial risk of bias. Evidence of the effect of oral corticosteroids without antibiotics is derived from only one high-quality trial and we therefore judged the quality to be moderate (further research is likely to have an important impact on our confidence in the effect estimate and may change the estimate).
+We searched for evidence of benefits and harms of HRT in EOC, up to June 2019. We identified three studies involving a total of 350 women. We found that HRT may improve overall survival and may make little or no difference to progression-free survival. We are unsure about the effects on quality of life, incidence of breast cancer, transient ischaemic attack (also known as 'mini stroke'), cerebrovascular accident (stroke) and myocardial infarction (heart attack), as the certainty of the evidence was very low. There were no reports on the incidence of gallstones. The certainty of the evidence was low to very low for all outcomes, mainly due to the small number of participants and low numbers of adverse events reported. The certainty of the evidence is also reduced due to the high risk of bias of the included studies, meaning their results might overestimate or underestimate the true effect of the treatment. Hormone replacement therapy may improve the overall survival in women who are experiencing surgically induced menopause after treatment for EOC, but it may make little or no difference to survival without the disease getting worse. The overall certainty of these findings is low to very low, mainly due to a lack of information. This is a very important area for further research, which has the potential to make a big impact on many women.
+This review identified 16 studies investigating antibiotics for UTI in children. Results suggest that 10-day antibiotic treatment is more likely to eliminate bacteria from the urine than single-dose treatments; there was not enough data to draw conclusions about other treatment durations, or effectiveness of particular antibiotics. Although antibiotic treatment is effective for children with UTI, there are insufficient data to recommend any specific regimen.
+We identified and included in this review randomized controlled trials of adults that compared conventional mechanical ventilation in the face-down versus the face-up position. Reports from nine trials of 2165 participants (10 publications) show that prone ventilation did not appear to be of benefit for all participants requiring ventilation but identified some situations in which it may improve survival. One group of participants with the most severe lung damage appeared to have reduced mortality, as did participants who received treatment early and for prolonged periods. Complications were described. The most common of these were pressure sores and tracheal tube blockage or obstruction. Low blood pressure and abnormal heart rhythms were also seen. Clinicians need to be aware of these and to take preventative actions when possible. The application of prone position to all participants in intensive care who have low oxygen levels is not warranted, but some particular groups of participants, for example, those with especially low oxygen levels, would benefit from prone positioning. Further clinical trials would assist in clarifying potential benefits for such patient groups but further trials may not take place because of the very large treatment benefit observed in the most recent clinical trial of participants with very low oxygen levels. In the absence of new trials, meta-analysis of individual patient data may facilitate further assessment. The quality of the evidence for primary outcomes of this systematic review was low as a result of serious inconsistency and important potential bias. The evidence is current to 31 January 2014. We reran searches in CENTRAL, MEDLINE, EMBASE, CINAHL and LILACS in June 2015. Five new studies of potential interest were added to the list of "Studies awaiting classification" and will be incorporated into formal review findings during the review update.
+Eleven trials including 501 liver transplant recipients provided data for this review. The patients were randomised to receive different treatments including no treatment in these 11 trials. Long-term follow-up was not available in these trials. There were no significant differences in the proportion of patients who died, required retransplantation, developed graft rejection that required treatment, or increased liver damage (as evaluated using a microscope) between the groups in any of the comparisons in which these outcomes were reported. Quality of life and liver decompensation were not reported in any of the trials. There was a significantly higher proportion of participants who developed serious complications in the ribavirin plus peg interferon combination therapy compared with peg interferon monotherapy. There was no significant difference in the proportion of participants who developed serious complications or in the number of serious adverse events between the intervention and control groups in the other comparisons that reported serious complications. There is currently no evidence to recommend antiviral treatment for patients with recurrence of chronic hepatitis C virus infection either in primary liver transplantation or retransplantation. All the trials had high risk of systematic errors (that is, bias where was a potential to arrive at wrong conclusions because of the way the trials were conducted overestimating benefits and underestimating harms) and random errors (there was a potential to arrive at the wrong conclusions because of the play of chance). The overall quality of evidence was very low. Further randomised clinical trials at low risk of random errors or systematic errors are necessary to assess the long-term survival and other benefits of various treatment options in these patients.
+We searched the literature in January 2015 and found 12 studies involved 3094 participants. Of these, about 1800 were included in comparisons between ibuprofen 400 mg and placebo. Others involved lower doses of ibuprofen, or different types of ibuprofen, or were in comparisons with other active drugs. The outcome preferred by the International Headache Society (IHS) is being pain free after two hours. This outcome was reported by 23 in 100 people taking ibuprofen 400 mg, and in 16 out of 100 taking placebo. The result was statistically significant, but only 7 people (23 minus 16) in 100 benefited specifically because of ibuprofen 400 mg. The IHS also suggests a range of other outcomes, but few were reported consistently enough for them to be used. People with pain value an outcome of having no worse than mild pain, but this was not reported by any study. About 4 in 100 people taking ibuprofen 400 mg had an adverse event with ibuprofen, the same as with placebo. There were no serious adverse events. There are questions about how studies in this type of headache are conducted. These questions involve the type of people chosen for the studies, and the outcomes reported. This limits the usefulness of the results, especially for people who just have an occasional headache.
+We searched for studies of people of any age, but this review only includes one study in which 170 babies with cystic fibrosis, aged less than six months, were divided into two groups completely at random. One group was given antibiotics based on samples taken by bronchoscopy and the other group based on samples taken from throat. The investigators measured outcomes at five years of age. A total of 157 children completed the study. This study did not show any difference between the groups in terms of lung function, weight, body mass index or in the score calculated by a CT scan of the lungs at five years of age. There were no differences in how many children in each group had an infection with Pseudomonas aeruginosa at five years of age, or per year of follow up, or how often a child was unwell with respiratory symptoms. Children in the bronchoscopy group were admitted to hospital more often although admissions were generally shorter than the other group. There was no difference in the overall cost of care between the two groups. Side effects reported during, and after bronchoscopy, were not serious; the most common side effect was increased coughing (in one third of children). There is currently not enough evidence to support the regular use of bronchoscopy to diagnose and treat lung infections in children with cystic fibrosis. Evidence was limited to only one well-designed study. Overall quality of evidence was of low (for most outcomes) to moderate quality (for high-resolution computed tomography scoring and cost of care analysis). Quality limitations were due to fewer children taking part in the study than the statisticians thought were needed to show true results for some outcomes. Since the treatment of a first infection with Pseudomonas aeruginosa is highly successful, larger and longer studies are needed to detect small differences between the groups. Conducting such large studies is extremely difficult. Also, the study only included young children and we do not know if the results would be the same in other age groups.
+Six randomised controlled trials, involving 202 participants, were analysed. Interventions ranged from five weeks to six months duration. Participants receiving the low glycaemic index or load diet lost a mean of one kilogramme more than those on comparison diets. Lipid profile also improved more in participants receiving the low glycaemic index or load diet. No study reported adverse effects, mortality or quality of life data.
+For this update (most recent search performed 11 June 2018), we found five more studies, giving us a total of 11 studies involving 2392 participants. Our updated review found that locking catheters with heparin may or may not prevent blocking better than flushing with normal saline. We saw little or no difference in duration of catheter patency (length of time catheter remained unobstructed), rate of infection, mortality, bleeding, or heparin-induced fall in platelet count (thrombocytopaenia). We detected no effect with increasing concentrations of heparin dose. The quality of the evidence ranged from very low to moderate for the main outcomes. We downgraded the quality of evidence owing to risk of bias and imprecision, as the pooled result included an effect of both benefit and harm and the suggestion of publication bias. To sum up, we are uncertain on the effects of heparin compared to normal saline and the findings should be interpreted with caution.
+We searched the medical and dental literature up to 8 May 2017. We found four relevant studies known as randomised controlled trials (RCTs), with 307 participants aged 31 to 85 years. All participants had previously been treated for moderate to severe chronic periodontitis and enrolled in a SPT programme for at least three months. Studies evaluated participants for at least 12 months after starting their SPT programme. The studies compared: additional use of an antibiotic (doxycycline in one study, minocycline in another) to professional cleaning (debridement); additional use of photodynamic therapy to debridement only, and SPT provided by a specialist versus a general dentist. We did not identify any RCTs comparing the effects of providing SPT versus monitoring only, the effects of SPT provided at different time intervals or the effects of mechanical debridement using different approaches or technologies. None of the studies reported tooth loss. However, studies evaluated signs of inflammation and potential periodontal disease progression, including bleeding on probing, clinical attachment level and probing pocket depth. The very limited amount of evidence did not provide evidence of one approach being better than another to improve tooth maintenance during SPT. Low- to very low-quality evidence suggests that adjunctive treatments may not provide any additional benefit for SPT compared with mechanical debridement alone. Evidence of very low quality suggests that SPT performed by general dentists under specialised prescription may be as effective as specialised treatment. Overall, there is not enough evidence available to recommend a certain approach or additional treatment in SPT to maintain teeth, promote gum health and prevent relapse. There were only four small studies, and only one of them was at low risk of bias. We judged the evidence to be of low or very low quality, therefore we cannot be confident in any conclusions drawn from the studies' results. We found insufficient evidence about the best approaches to SPT, and no RCTs evaluated SPT versus monitoring only. The evidence we found was low to very low quality, and studies used different methods to report their results, making comparison difficult. More studies are needed that report their findings in a uniform manner.
+We searched scientific databases for studies that examined protocol-directed sedation in adult and paediatric intensive care patients. We identified four studies with 3308 participants (864 adults and 2459 paediatrics) to include in this review. All of these included studies compared the use of protocol-directed sedation delivered by nurses to usual care (that is, non-protocol-directed sedation). There was no difference in the length of time mechanical ventilation was needed or in ICU or hospital deaths between people who received protocol-directed sedation and those people managed with usual care. There was a significant reduction in the number of days people treated with protocol-directed sedation spent in hospital, when compared to those managed with usual care. There was no difference between the two groups in the number of people who accidentally removed their breathing tube or required their tube to be reinserted after accidentally removing it. In conclusion, the benefits of protocol-directed sedation delivered by nurses compared to usual care are currently unclear in relation to the important outcomes of length of time mechanical ventilation was needed or number of deaths. The evidence available to answer our review question is low to moderate. This is mainly due to the often conflicting results that were reported from the four eligible studies. Further studies need to be conducted to determine the effectiveness of this intervention.
+We found 46 trials that randomly assigned participants to take either an ARB or an inert substance (placebo). These trials evaluated the BP lowering ability of 9 different ARBs in 13 451 participants altogether. The trials followed participants for only 7 weeks (though people are typically expected to take anti-hypertension drugs for the rest of their lives). The blood pressure lowering effect was modest.  There was an 8-point reduction in the upper number that signifies the systolic pressure and a 5-point reduction in the lower number that signifies the diastolic pressure.  Most of the blood pressure lowering effect (about 70%) can be achieved with the lowest recommended dose of the drugs.  No ARB appears to be any better or worse than others in terms of blood pressure lowering ability. Almost all of the trials in this review were funded by companies that make ARBs and serious adverse effects were not reported by the authors of half of these trials.  This could mean that the drug companies are withholding unfavorable findings related to their drugs.  Due to incomplete reporting of  the number of participants who dropped out of the trials due to adverse drug reactions, as well as the short duration of these trials, this review could not provide a good estimate of the harms associated with this class of drugs.  Prescribing the least expensive ARBs in lower doses will lead to substantial cost savings, and possibly a reduction in dose-related adverse events.
+Six trials (553 participants) were included in this review. Following analysis of the data, no significant change was seen in the loudness of tinnitus or the overall severity of tinnitus following the use of sound therapy compared to other interventions such as patient education, 'relaxation techniques', 'tinnitus coping strategies', counselling, 'tinnitus retraining' and exposure to environmental sounds. No side effects were reported from the use of sound-creating devices. The limited data from the studies included in the review failed to show strong evidence of the efficacy of sound therapy in tinnitus management, however the absence of conclusive evidence should not be interpreted as evidence of lack of effectiveness. There is a lack of quality research in this area and also combined approaches (hearing therapy plus counselling) are commonly used in the management of tinnitus. Optimal management of tinnitus may involve multiple strategies.
+The evidence in this review, which was carried out together with Cochrane Oral Health, is up-to-date as of 17 August 2016. We included four studies that evaluated 1037 participants, mostly children, who were undergoing different types of dental restorative treatments, using materials which require effective moisture control to reduce failure rates. For example, fissure sealing, resin or composite fillings at the gum margin, and proximal atraumatic restorative treatment in primary molars. All of the included studies compared the use of rubber dam and cotton rolls as two different isolation methods. There is some evidence to suggest that the use of a rubber dam may increase the survival time of dental restorations compared to the use of cotton rolls as an isolation method. The studies did not include possible side effects. The evidence presented is of very low quality due to the small amount of available studies, uncertain results and problems related to the way in which the available studies were conducted.
+This review has found no evidence of a difference between these two different operations for these outcomes. Surgery is faster with subtotal hysterectomy and there is less blood loss during or just after surgery, although these benefits are not large. With subtotal hysterectomy, women are less likely to experience fever during or just after surgery but are more likely to have long term ongoing menstrual bleeding when compared with total hysterectomy.
+This review evaluated the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of psychostimulants (PS) in the treatment of depression. Twenty-four RCTs were identified, of which 14 had data for meta-analysis. Five drugs were evaluated, including dexamphetamine, methylphenidate, methylamphetamine, pemoline and modafinil. Modafinil was evaluated separately as its pharmacology differs from other PS. Three small trials of PS involving a total of 62 participants indicated that oral treatment with PS in the short term (up to four weeks) significantly reduced depressive symptoms when compared with placebo, however, the overall quality of the trials was poor, limiting confidence in the findings. Two trials involving 411 participants compared modafinil against placebo when combined with antidepressant treatment at 6-8 weeks, and showed a non-significant difference in reducing depression symptoms. One small trial of 50 participants compared oral modafinil against placebo after 12 weeks of treatment, and also showed a non-significant difference in reducing depression symptoms. No trials examined the longer-term effect of PS. Further well conducted trials with long term follow-up are required to find out which PS may be more effective in the treatment of depression, and whether PS are more effective in certain subgroups of depressed patients.
+We searched for randomised controlled trials in March 2018. Our review includes 77 trials, involving 40,249 women and their babies, although it wasn't possible to include results form three of these trials (233 women) . We included information about the results for women and babies in two different formats: 36 trials (34,514 women) reported 'individual participant data' (IPD), where we received information about each of the individuals involved; all the other trials reported 'aggregate data' (AD), where each study reports the average information about the individuals involved in the study. By using IPD, we could conduct very thorough and accurate analyses; and by combining both the AD and the IPD, we could include all the available information on this question. Nine of the trials included more than 1000 women, and all of these large trials were at low risk of bias. Low-dose aspirin alone was the intervention in all the large trials, and most trials overall. Almost all the women were recruited to the trials after 12 weeks' gestation. Most women were at risk of developing pre-eclampsia, and the trials included women with normal blood pressure, existing long-term high blood pressure or pregnancy-induced high blood pressure. High-quality evidence showed that the use of antiplatelet agents reduced the risk of pre-eclampsia by 18%, or less than one sixth (36,716 women, 60 trials). This meant that 61 women had to be treated with an antiplatelet drug for one woman to benefit by avoiding pre-eclampsia. The risk of preterm birth was reduced by 9% (35,212 women, 47 trials) and the number of infant deaths before or around the time of birth was reduced by 15% (35,391 women, 52 trials). Antiplatelet agents reduced the risk of small-for-gestational-age babies (35,761 mothers, 50 trials) and pregnancies with serious adverse outcomes (17,382 mothers; 13 trials). Moderate-quality evidence showed that only slightly more women lost more than 500 mL of blood immediately after birth, termed postpartum haemorrhage (23,769 mothers, 19 trials), indicating that aspirin is safe. Doses of aspirin less than 75 mg appear to be safe. Higher doses might be better, but we do not know whether they increase adverse effects. What does this mean? Low doses of aspirin slightly reduce the risk of pre-eclampsia and its complications. As most women in this review were in trials evaluating low-dose aspirin, the reassurance about the safety of aspirin may not apply to higher doses or other antiplatelet agents. Further research should aim to identify women who are most likely to respond to low-dose aspirin treatment. While it is possible that higher doses of aspirin may be more effective, further studies are needed to determine whether higher doses are both more effective and safe for women and babies.
+Nine studies were reviewed. The studies compared TNF-alpha blocking agents with placebo (inactive intravenous infusions or injections) and found that infliximab, adalimumab, and certolizumab pegol were effective in maintaining remission in patients with Crohn's disease who respond to induction therapy with these agents. There is no evidence that CDP571 is an effective maintenance therapy. The TNF-alpha blocking agents appear to be safe for patients with Crohn's disease with equal numbers of patients receiving TNF-alpha blocking agents or placebo reporting side effects such as headache, abdominal pain, nausea, and pain at injection site. There were some serious side effects reported with the use of these agents including infections such as tuberculosis. However, patients can be screened for inactive tuberculosis prior to treatment with TNF-alpha. A link between long term treatment with TNF-alpha blocking agents and cancer is possible but not proven. Data obtained from observational studies including the Crohn's Therapy, Resource, Evaluation and Assessment Tool (TREAT) registry show no increased risk of cancer with the use of TNF-alpha blocking agents in patients with inflammatory bowel disease. The current evidence suggests that the TNF-alpha blocking agents infliximab, adalimumab, and certolizumab pegol are effective maintenance therapy in Crohn's disease. However, the use of these medications needs to be weighed against the potential risk of serious side effects, particularly infection.
+Due to the low number of studies and low quality of evidence, it was not possible to draw firm conclusions about the effectiveness of DMT for depression. It was not possible to compare DMT with medication, talking therapies, physical treatments or to compare types of DMT due to lack of available evidence. Key findings were: Overall, there is no evidence for or against DMT as a treatment for depression. There is some evidence to suggest DMT is more effective than standard care for adults, but this was not clinically significant. DMT is no more effective than standard care for young people. Evidence from just one study of low methodological quality suggested that drop-out rates from the DMT group were not significant, and there is no reliable effect in either direction for quality of life or self esteem. A large positive effect was observed for social functioning, but since this was from one study of low methodological quality the result is imprecise. Future studies should be of high methodological quality, comparing DMT with other treatments for depression, and include economic analyses.
+The authors of this review examined all research studies that report an evaluation of the effectiveness of motorcycle rider courses in reducing the number of traffic offences, motorcycle rider crashes, injuries and deaths. This review included 23 research studies, including three randomised trials, two non-randomised trials, 14 cohort studies and four case-control studies. The types of rider training that were evaluated varied in content and duration. The findings suggest that mandatory pre-licence training may present a barrier to completing a motorcycle licensing process, thus possibly indirectly reducing crash, injury, death and offence rates through a reduction in exposure to riding a motorcycle. However, on the basis of the existing evidence, it is not clear if (or what type of) training reduces the risk of crashes, injuries, deaths or offences in motorcyclists and the selection of the best rider training practice can therefore not be recommended. It is likely that some type of rider training is necessary to teach motorcyclists basic motorcycle handling techniques and to ride a motorcycle safely. It is therefore important that further research work be conducted to rigorously evaluate motorcycle rider training courses, particularly in low income countries where the main burden of motorcycle injuries and deaths occur.
+We examined the available evidence up to 13 April 2016 and included six trials with 590 people, which evaluated prednisolone given with antituberculous treatment (ATT). One included trial was of high quality, while the rest had uncertainties regarding trial quality. All the included trials were in adults; one trial included only HIV-positive people, two included only HIV-negative people, and three did not report the HIV status of the participants. Corticosteroids may reduce the time to resolution of the symptoms of TB pleurisy and the time to resolution of the pleural effusion on chest X-ray (low certainty evidence). Corticosteroids may also reduce the risk of having signs of pleural scarring on chest X-ray (pleural thickening and pleural adhesions) after the disease has resolved (low certainty evidence). There was not enough information about lung function to be sure whether or not corticosteroids reduce the risk of lung function impairment after TB pleurisy (very low certainty evidence). Corticosteroids may increase the risk of adverse events leading to discontinuation of the trial drug (low certainty evidence). From one trial in people living with HIV, there was no detectable increase in HIV-related conditions with corticosteroids, although cases of Kaposi's sarcoma were only seen in the corticosteroid group and numbers of participants and events were too small to rule out an effect of corticosteroids (very low certainty evidence). As the risk of disability and long-term illness after TB pleurisy is unclear, research looking at the association between TB pleurisy and lung function impairment would be useful to inform future research into corticosteroids for TB pleurisy.
+This review shows that ESAs improves anaemia, exercise tolerance, quality of life and reduces symptoms in heart failure patients with a mild anaemia. ESAs may also reduce hospital admission and improve survival. There was no increase in major side effects in those receiving ESA therapy compared to control over the 2-12 month study period (maximum 12 months) although the effects of treatment over a longer period are not known. More research is needed to clarify the full effects and safety of ESAs as a treatment for anaemia in these patients.
+Through literature searches up-to-date until Novebember 2016, we found only one small randomised controlled trial (with 64 very low birth weight infant participants) that addressed this question. Very low birth weight infants who receive more milk than standard volumes gain weight more quickly during their hospital stay. We found no evidence suggesting that giving infants high volumes of milk causes feeding or gut problems, but this finding is not certain. Available evidence is insufficient to support or refute the use of high-volume feeds in preterm or low birth weight infants. High-volume feeds might increase the rate of weight gain, but more trials are needed to confirm this finding and to examine whether high-volume feeds cause any problems for preterm or low birth weight infants.
+The review authors conducted extensive searches of the medical literature up to November 2014 for relevant randomized controlled trials (RCTs), which provide the most reliable evidence. They identified nine RCTs, involving 968 participants, that compared the use of external drains in some patients versus no drains in other patients after burr-hole surgery for CSDH. The trials were conducted in India, Turkey, Iran, Germany, the UK and Japan. All participants were adults, mostly over 60 years of age. All the trials used very similar surgical procedures. Six trials followed participants for six months, the remaining trials followed them for three months, one month, or three weeks (one trial each). The authors were able to pool the results of the trials statistically, and this showed that use of drains does reduce the risk of recurrence of CSDH after burr-hole surgery by about 50% compared to the risk in the group of patients who did not have drains (the control group). However, there were no clear differences between the drain and no-drain treatment groups for postoperative complications (i.e. infection, seizures or sudden bleeding), death, or functional outcome (i.e. regaining abilities affected by the CSDH). The results of this review may change in the future when data are available from additional studies. The existing studies have either too few participants or events to give a reliable result, even when the results are pooled. Some of the studies did not describe the randomisation procedures in detail, and are considered to be of lower quality because of this. Further research will also help to establish: - the effects of external drains on postoperative complications, death, and functional outcome; - whether it is better to use one or two burr holes during surgery; - the best way to position the drain’s tube within the brain; - the best duration of drainage.
+We considered only randomised controlled trials in this Cochrane Rapid Review, as they offer the most reliable results. This review is current to 20 June 2018. We found only one randomised study for our question. Participants included in this trial had metastatic (cancer that has spread to other parts of the body) or advanced cancer that could not be removed by surgery, that had come back or worsened with other chemotherapy. We found that pembrolizumab probably improves overall survival a little (evidence of moderate certainty). It may improve quality of life slightly (low certainty evidence). Pembrolizumab may have little or not effect on the time for the cancer to worsen or advance (low certainty evidence). It probably improves treatment response as seen on X-ray scans such as computer tomography (moderate certainty of evidence). Pembrolizumab may have little or no effect on deaths resulting from the treatment itself (low certainty evidence) but may result in fewer patients stopping treatment due to unwanted side effects (low certainty evidence). It may also cause less serious side effects. These conclusions are based on a single trial paid for by the company that makes pembrolizumab. The certainty of evidence ranged from moderate to very low.
+A total of 33 experimental studies were conducted across Africa and Central and South America, with most reported from Asia, specifically India, Pakistan, and Bangladesh. Of the 33 community educational interventions, 16 required involvement of family members, most frequently the mother-in-law or the expectant father. Most studies (n = 14) involved one-to-one counselling between a range of community healthcare workers and mothers, and 12 involved group counselling consisting predominantly of mothers, with family members included occasionally; the remaining seven had components of both one-to-one and group counselling. This review found that community health educational interventions significantly reduced newborn death, early newborn mortality, and late newborn mortality, as well as perinatal mortality. These interventions also positively impacted utilisation of any before birth (antenatal), care during pregnancy, and initiation of breastfeeding within an hour after birth. The review shows that educational interventions delivered to both mothers and other family members in a group setting had a greater impact on these outcomes. Educational interventions delivered during antenatal care were more effective for reducing early neonatal deaths, and those delivered during both antenatal and postnatal (after birth) periods were effective for reducing late neonatal deaths and perinatal deaths. Educational interventions during the postnatal period were most effective for improving breastfeeding practices. The quality of evidence is low for newborn mortality outcomes and very low for early, late, and perinatal mortality. This reflects concerns of bias, inconsistency (unexplained variability of results), and imprecision (variation in studies presenting both benefit and harm from the intervention) of the included randomised controlled trials.
+This review included eight randomised controlled trials of autoinflation for glue ear. All of the studies were small, of limited treatment duration and had short follow-up. The review authors used a combined outcome measure which included any outcome signifying improvement (as defined in the individual studies) and measured outcomes at the time points 'up to one month' and 'more than one month'. Improvement was demonstrated only in 'more than one month' analyses. Subgroup analysis based on the type of intervention showed a significant effect using a Politzer device at both under one month and over one month. None of the studies demonstrated a significant difference in the incidence of side effects between interventions. The authors conclude that the evidence for the use of autoinflation in the short term appears favourable. Given the small number of studies and the lack of long-term follow-up, the long-term effects associated with the use of these devices cannot be determined.
+This review looked to see if local cooling for a short period of time helped to relieve perineal pain for women and helped with healing. We found 10 studies including 1825 women that compared cooling treatments such as ice, cold gel pads, or cold bath with no treatment, or other treatments. One study found that women reported less pain 24 to 72 hours after giving birth when they used the ice packs for 10 to 20 minutes, rather than when they had no treatment. No effect on healing was identified. There is only a small amount of evidence of how safe and effective cooling treatments are to relieve perineal pain.
+We found 21 RCTs involving more than 6300 people with Alzheimer’s disease. Four trials of two different medicines (methylphenidate and modafinil) had been done specifically to study apathy, so all the people taking part were known to be significantly apathetic before the trial started. The other 17 trials had other primary aims, but reported some data on apathy. The trials were generally well designed and conducted. From the three trials with methylphenidate, we found that it may improve apathy, although this depended on how the apathy was measured. The people taking methylphenidate also did slightly better than those taking placebo on scales measuring cognition (thinking, remembering, etc.) and some daily activities, but it was not clear that these effects were big enough to be important in practice. We found no evidence that it caused more side effects than placebo. The quality of this evidence was low or moderate, so we cannot be certain that other similar studies would not have different results. There was only one very small trial with modafinil and there was no evidence that it was effective for apathy. The other 17 trials studied a variety of medicines and included people who were not necessarily significantly apathetic to start with. We therefore thought they were only indirectly relevant to our review question. It is also highly likely that other trials of the same drugs have measured apathy but have not published the results, so we were concerned about possible publication bias (that the studies we found could have been a biased subset). We therefore thought the quality of evidence for all these other medicines was low or very low, meaning that we can have limited or little confidence in the results. Current evidence suggests that methylphenidate may be useful for treating apathy in Alzheimer's disease. However, more trials should be done specifically targeting apathy in order to improve the overall quality of the evidence.
+Three studies were found that met our criteria. The double wall incubators had advantages as far as decreasing heat loss and decreasing heat production. These infants seemed to be in the best temperature range, as their need to burn energy was less. However, these effects were small and did not provide any evidence of any long-term improvement regarding duration of hospitalization or survival. Although it appears that caring for extremely small infants in double wall incubators may result in certain metabolic advantages, this review was unable to find any data in the literature to support or refute this theory. Available data is insufficient to directly guide clinical practice.
+We included six randomised, double-blind trials from five publications involving a total of 387 participants published between 1987 and 1995 in the English language. All included trials used the RhinoTherm device, which delivered heated, humidified air for different lengths of time and at different flow rates to treat common cold symptoms. Three trials were conducted in the USA, two in the UK, and one in Israel. Most studies recruited people with naturally occurring colds, but one study induced colds by infecting participants. The RhinoTherm devices were provided by Netzer Sereni in four studies and A Beacham in two studies. One study was funded by Cleveland Clinic internal funding, and another was supported by authors' discretionary funds. The remaining studies did not mention funding sources. None of the included studies reported any worsening in clinical symptom scores after inhaling heated, humidified air. Participants in two trials showed a lack of persistent symptoms, however the results were inconsistent. Two studies reported minor adverse events. There was no effect of treatment on rhinovirus shedding. Using GRADE criteria, we assessed the quality of the evidence as low for the outcomes reduction in the clinical severity of the common cold (measured by decrease in the symptom score index); number of participants with the subjective response: therapy did not help; and number of participants with a positive viral culture in the nasal washings, due to risk of bias and inconsistency of the study results.
+We found four trials with a total of 167 participants, two of which compared inhaled antibiotics alone to intravenous antibiotics alone (77 participants) and two which compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone (90 participants) for treating exacerbations in people with cystic fibrosis. In all trials the inhaled antibiotics were compared to the same antibiotics given intravenously. The numbers of participants in each trial ranged from 18 to 62. Inhaled antibiotics alone versus intravenous antibiotics alone One trial (18 participants) reported a perceived improvement in lifestyle in both groups but neither trial reported on time off work or school. Both trials measured lung function, but neither reported any difference between treatment groups. One trial (18 participants) reported no difference in the need for additional antibiotics and the second trial (59 participants) reported on the time to next exacerbation - there was no difference between inhaled or intravenous antibiotics for either outcome. Only one trial (18 participants) measured adverse events and sputum microbiology, but did not find any difference between treatments for either outcome. Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics alone Neither trial reported on quality of life or time off work or school. Both trials reported lung function, but found no difference between groups. Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (28 participants) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events and one trial (62 participants) reported no difference in the emergence of antibiotic-resistant organisms. We graded the quality of the evidence as very low. We had concerns since none of the trials stated how the participants were diagnosed with CF or how they defined an exacerbation. It was not possible to keep the treatment group secret from the participants as the trials compared different ways of giving the antibiotics and we thought this would likely influence some of the results. We were not sure whether the participants were put into the different groups truly at random and we do not know how this might affect the results.
+We reviewed 23 studies of different designs involving 188,934 young people and conducted in the United States, Canada and Australia. The studies tested different interventions and used several questionnaires to interview the young people about the effects of having participated in the studies brought to them. As a result it was very difficult to reach conclusions and for this reason we are highlighting the need for further studies.
+This review assessed the effects of providing dietary advice to healthy adults in order to produce sustained improvements in their diets. Whether dietary improvement would reduce the risk factors associated with heart disease was also examined. We found 44 trials in which healthy adults were randomly assigned to receive dietary advice or no dietary advice. The dietary improvements recommended to the people in the intervention groups centred largely on the reduction of salt and fat intake and an increase in the intake of fruit, vegetables and fibre. Advice was delivered in a variety of ways, including one-to-one contact, group sessions and written materials. There were variations in intensity of the intervention, ranging from one contact per study participant to 50 hours of counselling over four years. The duration of the trials ranged from three months to four years, with a median follow-up period of 12 months. There was some evidence of greater effectiveness in people told that they were at risk of heart disease or cancer. Modest improvements were shown in cardiovascular risk factors, such as blood pressure and total and LDL-cholesterol levels. In the trials that separated effects by gender, women tended to make larger reductions in fat intake but there was insufficient evidence to show whether this translated to a larger reduction in total cholesterol levels. Two trials followed people up 10 to 15 years after the end of the trials and showed that the beneficial changes in cardiovascular risk factors may have resulted in a reduced incidence of heart disease, stroke or heart attack, although more evidence is needed to confirm this.
+We have reviewed clinical trials evaluating the efficacy and safety of abacavir-containing triple nucleoside combination as a simplification therapy in HIV-infected adult patients treated with a Protease-Inhibitor (PI)-containing regimen and  with undetectable viral load. Patients on a PI-containing regimen had three possibilities: continue the PI regimen or switch to a simplification maintenance regimen with triple nucleoside combination (abacavir-zidovudine-lamivudine) or with non-nucleoside (efavirenz or nevirapine) containing regimens. The review included 8 RCTs and 1675 HIV infected patients. Simplification with triple nucleoside regimen showed an overall failure rate comparable to that of  continuing  PI regimen or  to simplification with non-nucleoside regimens. Rates of failure due to adverse events with triple nucleoside combinations were lower compared to controls, but the difference was not statistically significant. By contrast, rates of virologic failures   were more frequent with  triple nucleoside combination that with PI or NNRTI, but in both the comparisons the differences were  not statistically significant. Simplification with abacavir had a favourable and significant impact on lipid metabolism compared to control group. Simplification with triple nucleoside regimens should be still considered for individuals who are unable to tolerate or have contraindications to NNRTI or PI based regimens
+We identified four randomised studies involving only 362 women with hypothyroidism. In one trial of 115 women with thyroid autoantibodies but normal thyroid hormone levels, levothyroxine clearly reduced the risk of preterm birth by 72% compared with no treatment. The risk of women developing pre-eclampsia was not reduced, but there was a trend toward a reduction in miscarriage. In a study of 169 women with autoimmune hypothyroidism, supplementation with selenium did not decrease preterm birth rates or pre-eclampsia, but appeared to reduce moderate to severe inflammation of the thyroid gland and thyroid dysfunction after the birth. The third and fourth studies looked at different doses of levothyroxine on thyroid hormone levels. Levothyroxine is an established treatment for women with symptomatic hypothyroidism, but it may also benefit women with low thyroid levels who do not have symptoms. Selenium also shows promise for women with hypothyroidism but needs further testing.
+In June 2016, we found 50 studies that tested 39 different drugs in 1916 people with itch. An ideal antipruritic (anti-itch) therapy is currently lacking. However, there was enough evidence to point out some possibly useful treatments for particular causes of the itch. These included gabapentin, nalfurafine and cromolyn sodium for itch associated with chronic kidney disease, and rifampicin and flumecinol for itch associated with liver problems. Paroxetine may be useful for palliative care patients whatever the cause of the itching, although evidence was only available from one study. Overall, most of the drugs caused few and mild side effects. Naltrexone showed by far the most side effects. Overall the evidence ranged from very low to moderate quality. Research in palliative care is challenging and often limited to a restricted period of time at the end of life. More high-quality studies on preventing and treating itch (pruritus) are needed.
+We found five randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups) with 244 participants. A total of 127 participants were randomised to retroperitoneal adrenalectomy and 117 participants to transperitoneal adrenalectomy. Two studies had an observation period after surgery of nine months. Three studies observed their participants for 31 to 70 months. Most participants were women, and the average age was around 40 years. This evidence is up to date as of April 2018. In the short-term period after surgery, no deaths were reported for either adrenalectomy technique. One study with a six-year observation period, reported that out of 164 participants, four participants from the retroperitoneal adrenalectomy group died, and one participant from the transperitoneal adrenalectomy group died. We compared early poor health (morbidity), reported after 30 to 60 days, and late morbidity, reported at the longest observation time after surgery. Early morbidity was comparable between the two techniques, but late morbidity might be lower following retroperitoneal adrenalectomy (none out of 78 participants) than following transperitoneal adrenalectomy (7 out of 68 participants). No study reported on health-related quality of life. Time to return to normal activities, length of hospital stay, duration of surgery, operative blood loss, and a change to open surgery were comparable between the two techniques. Time to oral fluid or food intake and time getting out of bed and engaging in light activity seemed a couple of hours shorter following retroperitoneal adrenalectomy (on average 8.6 hours) compared to transperitoneal adrenalectomy (on average 5.4 hours). We are uncertain which adrenalectomy technique is best, mainly because of the small number of studies, small number of participants, and some systematic errors in the majority of our analysed studies. New studies should especially investigate health-related quality of life. Surgeons' level of experience and treatment volume of surgical centres might also influence results.
+Six studies, published between 2006 and 2014, were included in this review, comprising a total of 5152 participants suffering from RRMS. The treatment duration was six months in three studies, 12 months in one study, and 24 months in two studies. The main conclusion of this review was that fingolimod, administered as monotherapy at the approved dose of 0.5 mg once-daily increases the probability of being relapse-free at 24 months compared to placebo. The benefit was confirmed with disease activity measures defined by magnetic resonance imaging (MRI) scans. However, there was no effect on preventing disability worsening; treatment was not associated with an increased risk of patient withdrawals due to adverse events. Comparing the same dose of fingolimod to intramuscular interferon beta-1a, the drug at one year slightly increased the number of participants free from relapse or from inflammatory enhancing lesions and decreased the relapse rate. Again, we did not detect any advantage for preventing disability progression. We found a greater likelihood of discontinuation due to adverse events in the short-term (six months) for fingolimod as compared to immunomodulating drugs, and no significant difference compared to interferon beta at 12 months. The duration of all studies was equal or inferior to 24 months, so that the efficacy (but mostly the safety) of fingolimod over 24 months remains uncertain. This is a key point for a lifetime disease with the probability of chronic treatments as in MS. The risk of adverse events requires careful monitoring of patients over time and suggests the need for studies with longer follow-up, particularly considering the recent warning on the development of progressive multifocal leukoencephalopathy. The six studies included in this review were sponsored by Novartis Pharma, and most co-authors of the published papers were affiliated to the pharmaceutical company; this is recognised as a potential source of bias.
+The update search in 2012 detected two further studies that met required standards, and no further studies were found in the 2015 search. This review now includes 22 randomised studies, with a total of 763 participants. The studies randomised people with schizophrenia or similar illnesses into groups that received either lithium or placebo (dummy drug), lithium or antipsychotic drugs, lithium plus antipsychotic drugs, or antipsychotic drugs alone. The findings in this review show that there is no good quality evidence that lithium on its own is effective for people with schizophrenia or schizoaffective disorder. There is some low quality evidence for the effectiveness of lithium as an add-on treatment with antipsychotic drugs, but this result is inconclusive. Few studies reported on the side effects of lithium (such as kidney and thyroid problems). Most of the studies were small, of short duration, and poorly reported. The review authors rated the quality of evidence for the main outcomes to be low or very low quality. Further large and well-designed trials are needed. Ben Gray, Senior Peer Researcher, McPin Foundation (http://mcpin.org/), wrote this plain language summary.
+Randomised clinical trials have compared three types of portosystemic shunting separately against endoscopic therapy. The shunts included in these trials have been total portocaval shunts, distal splenorenal shunts, and transjugular intrahepatic portocaval shunts. The authors found that when compared to endoscopic therapy all three types of shunt lowered the rate of rebleeding at the cost of a higher incidence of hepatic encephalopathy, without any statistically significant difference in survival.
+We searched for evidence in the literature until June 2018 and identified a total of 16 studies. Studies were included if a routine calcitonin test (with or without the stimulation test) was performed in all included people with thyroid nodular disease. In total 72,638 people with thyroid nodular disease were enrolled in the analysed studies, of which 187 had medullary thyroid carcinoma. Our findings indicate that both basal and stimulated calcitonin testing are able to detect nearly all people with medullary thyroid carcinoma. However, because medullary thyroid carcinoma is very rare in persons with a thyroid nodule, there is large chance that calcitonin levels are false positives (i.e. the test indicates the disease, whereas in fact there is none). In practice this means that for every 10,000 persons with thyroid nodular disease, 23 persons will have medullary thyroid carcinoma. Of these, none will be missed using a basal calcitonin threshold of 10 pg/mL, while 280 people will have a false-positive test result. This might lead to unnecessary surgery of the thyroid with the need for life-long thyroid hormone supplementation and risk of complications. With the use of a stimulation test the chance of a false-positive test result may be reduced, however due to lack of sufficient studies this could not be calculated. The certainty of the evidence is importantly limited, because almost all studies did not report adequately on the outcome of people who had a negative calcitonin test. A number of patients who had medullary thyroid carcinoma were possibly not identified. The diagnostic accuracy can already be markedly affected when a small number of patients is missed because medullary thyroid carcinoma is very rare. Based on the available literature, there is insufficient evidence for a routine calcitonin test in all people with a thyroid nodule. Further studies are needed, with also adequate reporting of the people who have a negative calcitonin test, to determine the role of the calcitonin test in people with thyroid nodules for detection of medullary thyroid carcinoma.
+This review includes three trials and 112 women with uterine fibroids under mifepristone treatment. These clinical trials included a small number of participants and show limited methodological quality. The studies included in this review show that mifepristone had a moderate effect in relief of bleeding and showed an improvement in fibroid-specific quality of life. Determination of the effects of mifepristone on uterine fibroid volume requires much larger trials to draw a confident conclusion for mifepristone in clinical use.
+Through literature searches updated to December 2016, we found six studies that enrolled 1041 preterm babies and tested the role of lactoferrin along with feeds. We also found large ongoing studies that may increase the strength of our findings when their results become available. Evidence of low quality suggests that oral lactoferrin with or without a probiotic decreases blood infection and NEC in preterm infants with no adverse effects. Clarification regarding dosing, duration, type of lactoferrin (human or bovine), and development of preterm babies is still needed. Evidence is of low quality.
+This review is an update of a review previously published in 2011 that included 18 studies, enrolling 14,303 patients. The update of this review did not identify any new studies for inclusion. We did not find a significant risk reduction for all-cause mortality, heart attack, or stroke within the first four months. We had some concerns about risk of bias and imprecision of the results. The risk of unstable angina was reduced by about 25% at four months following acute coronary syndrome. Serious side effects from early treatment with statins were rare (0.1%), and serious muscle toxicity was mostly observed with simvastatin 80 mg.
+We searched for all relevant studies up to November 2015. Forty studies compared the HPV test to the Pap test on over 140,000 women between 20 to 70 years old who attended for their routine cervical screening. The studies examined which test can detect precancerous cervical changes which are called cervical intraepithelial neoplasias (CIN 2 and CIN 3). There were enough studies with enough women in them to allow us to draw conclusions. However, some of the results from the studies were different from each other. For example, tests were more accurate in studies in Europe than in Asia or Central or South America. Overall, the quality of the evidence was moderate to high. A perfect test would correctly say if a woman has precancerous changes or if a woman does not. But most tests are not perfect. This review found that for every 1000 women screened, around 20 women will have precancerous changes. The HPV test will correctly identify 18 of these women (but will miss 2 women). The Pap test will identify 15 of the women (but will miss 5 women). The women who are missed could develop cervical cancer. For every 1000 women screened, there will be 980 women who will not have precancerous changes. The HPV test will correctly identify 881 women (but 99 women will be incorrectly told that they have a lesion). The Pap test will correctly identify 885 women (but 95 will be incorrectly told that they have a lesion). Women who are incorrectly told that they have a lesion may have their cervix examined or may receive surgery unnecessarily.
+This review focuses on the effects of information programs which provide information specifically related to the facility and the services available to patients, their families and care givers. A broad search of published reports located only four studies with 610 participants which met the criteria for inclusion in this review. Orientation interventions may reduce distress in patients, but the quality of the evidence is low. The effects of such intervention on patient/carer satisfaction, knowledge and recall were not sufficiently evaluated or reported by the included trials. Although the studies generally reported positive outcomes for participants (e.g. more knowledgeable about the cancer centre and cancer therapy, better coping abilities), the studies generally were of poor quality and did not have a sufficient number of participants to eliminate the possibility of bias.
+We found 47 studies that were published up to May 2017. These studies involved 17,039 adults who had major surgery. Twenty-four studies involved 2672 adults having heart surgery. Twenty-three studies involved 14,367 adults undergoing major operations other than heart surgery. Forty studies compared alpha-2 adrenergic agonists to dummy treatment (placebo). The other seven studies compared them to other medicines. Twenty-one studies tested an alpha-2 adrenergic agonist medicine called clonidine, 24 studied another medicine called dexmedetomidine and two studied another medicine called mivazerol. The duration of alpha-2 adrenergic agonist medicine studied varied from one dose before surgery to three days of treatment. Most people who took part in these studies were men, and their average age was 60 to 70 years old. Fourteen studies reported receiving money from the company that manufactured the medicine being tested in the same study. Another 15 studies did not report where they received the money needed to fund the study. The number of people who took part in each study varied between 20 participants to as many as 10,000 participants. Nineteen studies included more than 100 participants. We found that alpha-2 adrenergic agonists generally had no clear benefits for preventing death or major complications after surgery. For people having major operations other than heart surgery, alpha-2 adrenergic agonists did not lower their chances of dying, having a heart attack or having a stroke after surgery. We did not find sufficient evidence that, in people having heart surgery, alpha-2 adrenergic lowered the risk of dying or having a heart attack after surgery. There was some very limited evidence that these medicines might prevent strokes after heart surgery. Nonetheless, more research is needed before we can be certain that alpha-2 adrenergic agonists truly have this benefit. These medicines also had some important side effects. People who received alpha-2 adrenergic agonists were much more likely to have low blood pressures or low heart rates during or after surgery. We assessed the quality of all studies we identified using a specialized tool called the GRADE criteria. In general, we found that most of the evidence in these studies was moderate or high quality. Thus, based on our results, we can be reasonably certain that alpha-2 adrenergic agonists are not helpful for reducing the numbers of deaths or major heart complications that happen after surgery.
+Antiplatelet agents like aspirin are effective for preventing serious vascular events in patients with atrial fibrillation not suitable for oral anticoagulants. Atrial fibrillation is an irregularity of the heartbeat that leads to blood clots forming in the upper chambers of the heart (the atria). These clots can break free and travel through the bloodstream to the brain and cause a stroke. Drugs that slow clotting, such as antiplatelet agents (aspirin and others) and anticoagulants reduce the risk of stroke in patients with atrial fibrillation. In this review the benefits of antiplatelet agents are shown to be modest (nearly 25% decrease in stroke), but they are relatively safe, easy to take, and therefore an important treatment option for many atrial fibrillation patients. Anticoagulation with warfarin and related drugs offers more protection against stroke (nearly two-thirds reduction), but anticoagulant drugs can cause severe bleeding and require careful regulation with regular blood tests. The choice of antiplatelet drugs versus anticoagulants should be individualized based on the patient's inherent risk of stroke, ability to tolerate anticoagulation without bleeding, access to adequate anticoagulation monitoring, and patient preferences.
+The review included 40 studies with 1717 people with cystic fibrosis. Studies compared intravenous antibiotics with placebo (dummy drug with no active medication) and also one antibiotic compared to two antibiotics given together. Specific antibiotic combinations were also compared as were intravenous antibiotics with antibiotics that were breathed in (inhaled) and antibiotics that were swallowed (oral). The studies lasted from three to 15 days, although most of the studies lasted for two weeks. In the comparison between those people who were given just one antibiotic and those who were given two, it appeared that those receiving two antibiotics experienced a greater improvement in lung function, but when limited to only those studies that included a dummy drug, we did not see any difference. There was no effect upon the amount of time until the next exacerbation, weight, or adverse effects. No combination of antibiotics was any better than any other. The outcomes for people were the same irrespective of whether they were treated by intravenous, oral or inhaled antibiotics. None of the studies reported on quality of life. The quality of the included studies was often poor and many were not properly reported. Some studies included volunteers more than once which made comparing treatments difficult. It was also often difficult to decide from the information given how well the studies were carried out - particularly with respect to how volunteers were chosen and whether the volunteers or doctors could tell which treatment they were being given.
+We conducted a review to determine the effectiveness of adding oxygen to exercise training in comparison to exercise training without oxygen supplementation in people with COPD. Five studies addressed the question although, because of measurement of different outcomes, the maximum number available for looking at any individual outcome was three (31 patients receiving oxygen versus 32 not). People with COPD may exercise longer and have less shortness of breath when using oxygen during an exercise-training program. These studies did not look at the effect of oxygen on shortness of breath in daily life. From the evidence to date, it is not possible to determine whether individuals with COPD should use oxygen during exercise training. Stronger studies with more participants are required in order to understand how oxygen-supplemented exercise training for people with COPD will affect their shortness of breath, activity and quality of life.
+We therefore conducted a systematic review and meta-analysis of 10 randomized controlled trials including 2072 patients. Our main results showed that any maintenance treatment compared to observation prolongs the freedom from disease duration but not overall survival. Similarly, ATRA and chemotherapy compared to ATRA alone improves freedom from disease duration but not overall survival. Moreover, ATRA-based regimens compared to non-ATRA based regimens probably improves freedom from disease duration but not overall survival. Finally, we showed that any maintenance treatment compared to observation as well as maintenance combining ATRA and chemotherapy compared to ATRA alone are more toxic, potentially limiting patient adherence to treatment. Our results imply that in patients with newly diagnosed APL, ATRA-based maintenance therapy may be added to the standard therapy in order to improve freedom from disease. Yet, one should bear in mind that this treatment does not improve overall survival and adds toxicity. Our results are limited mainly by the diversity of trials in terms of maintenance regimens and treatments antedating maintenance administration. Additionally, quality of life (QOL) parameters were not reported, and therefore are worth evaluating in future trials since maintenance therapy has a direct impact on QOL.
+This review included three trials evaluating two different types of steroids, triamcinolone acetonide and anecortave acetate, for the treatment of neovascular AMD. The findings across the three trials, which included a total of 809 participants, were consistent with no evidence of benefit, in terms of preventing vision loss, with antiangiogenic steroids compared with placebo or photodynamic therapy. Based on available evidence, there is little benefit of steroids with anti-angiogenic properties in the treatment of neovascular age-related macular degeneration. ".
+We identified two clinical trials that included a limited number of patients comparing ruxolitinib to placebo or standard medical treatment. Both studies were published in 2012, and were conducted in the United States of America (USA) and the United Kingdom (UK). Drug companies sponsored both trials. Although the results of the studies only showed a moderate improvement of patients treated with ruxolitinib in terms of their quality of life and a reduction in their spleen size, we could not be sure whether these effects were reliable because of the limitations of the studies and the low number of people they recruited. We also could not be sure whether the drug has an effect on overall survival compared with a placebo, or when it was compared with an active treatment. The effect of ruxolitinib in terms of progression-free survival was also uncertain. In addition, people treated with this drug showed higher rates of anemia, thrombocytopenia and neutropenia compared with patients treated with a placebo, but the rate of adverse effects was similar to those treated with a medical treatment. The confidence in the results of this review is very low. The studies have limitations in the way they were designed and executed. Moreover, the limited number of patients included in the studies led to imprecise results. Larger studies should provide more information about the effect of ruxolitinib. Researchers from Cochrane searched all available literature up to 13 November 2014.
+The purpose of this review was to assess whether the use of intravenous aminophylline in children receiving maximised inhaled bronchodilators and glucocorticoids produced additional beneficial effects. We identified a small number of good quality trials which compared aminophylline with placebo in children given inhaled bronchodilators and glucocorticoid therapy. This review found evidence that children treated with aminophylline had a greater improvement in lung function than children treated with placebo, when both groups received inhaled bronchodilators and steroids and they responded incompletely to these initial therapies. However, aminophylline use also resulted in greater risk of vomiting. Aminophylline use in children may be appropriate if children have a role in severe acute exacerbations of asthma where response to maximised therapy (inhaled bronchodilators and glucocorticoids) is poor. These results are based on small numbers and further work in this area is required.
+We found eight studies out of 1326 publications, covering 52,746 participants. One of these studies is new to this updated version of the review. The most recent search was conducted in June 2016. All studies were directed at youth younger than 25 years. Seven studies were conducted in the USA and one was conducted in Norway. The mass media method (e.g. television) and certain characteristics of those taking part (e.g. age), as well as the length of time followed up, differed between studies. Three out of eight studies found that the intervention was effective in preventing smoking in youth. The remaining five studies did not detect an effect. Although there was some overlap in characteristics between both effective and ineffective programmes, effective campaigns tended to last longer (minimum 3 years) and were more intense (more contact time) for both school-based lessons (minimum eight lessons per grade) and media spots (minimum four weeks' duration across multiple media channels with between 167 and 350 TV and radio spots). Implementation of combined school-based components (e.g. school posters) and the use of repetitive media messages delivered by multiple channels (e.g. newspapers, radio, television) appeared to contribute to successful campaigns. The quality of studies in this review is limited, due to problems in reporting results and issues with study design. Studies varied in their design, the interventions they tested, and in the people they involved. Studies found mixed results. In particular, none of the studies reported blinding of groups and there were concerns around how the studies were allocated to intervention or control. It would therefore be unwise to offer firm conclusions based on the evidence in this review. Inclusion of only two studies from the last 10 years is concerning, particularly considering the rising use of social media among youth. More high-quality studies are needed.
+The review authors included 15 trials of 4377 adults and children older than one year with vivax malaria. All were treated with chloroquine for the blood stage infection, and then randomized to the 14-day primaquine course, or to shorter primaquine courses (three, five, or seven days); or to higher doses of primaquine given once a week for eight weeks; or to a placebo or no treatment. In twelve studies, treatments were supervised. The evidence is current to 8 October 2013. Relapse over six months to one year is probably higher with shorter regimens when compared to the standard 14-day primaquine regimen (moderate quality evidence). We do not know from the available evidence whether the number of relapses with weekly primaquine differs from 14 days of primaquine treatment based on one study of 126 people followed up for nine months (very low quality evidence). Better conducted studies on more people are needed to be sure that they are equally effective against relapse. Five days of primaquine was as ineffective against relapse as placebo or no treatment over six months to 15 months based on four studies (high quality evidence). The 14-day primaquine course prevented many more people relapsing with vivax malaria over 12 months than placebo (high quality evidence). No serious adverse reactions to primaquine were reported. This review update confirms that the 14-day primaquine course recommended by the WHO is more effective against relapse of vivax malaria than treatment with shorter courses of primaquine.
+Drugs commonly used to treat schizophrenia often cause sexual problems.This may affect erection, lubrication, orgasm, desire or libido, ejaculation, sexual arousal or overall sexual satisfaction. This may have serious negative consequences such as putting people off taking their medication or stopping taking drugs at an early stage. Sexual problems may limit a person’s quality of life, worsen self-esteem and cause relationship problems.Strategies to manage these sexual problems are taking additional drugs (Viagra TM), short drug holidays when people temporarily stop antipsychotic medication, reduction of dose and switching to another antipsychotic drug. This review includes four pioneering studies with a total of 138 participants lasting between two weeks to four months, meaning all were small and quite short. Two of the studies compared the effects of drugs to treat sexual problems and two compared the effect of switching to a different antipsychotic drug (while remaining on a current antipsychotic). There is some evidence that sildenafil ((ViagraTM, RevatioTM)) may be a good treatment for men who have problems getting and maintaining an erection. It also seems to increase frequency and satisfaction of sexual intercourse. Switching to olanzapine may improve sexual functioning in men and women. However, before confident claims can be made, much more research on strategies to deal with sexual problems should be undertaken. Sildenafil may be a useful option in the treatment of sexual problems in men with schizophrenia, but this conclusion is based only on one small, short trial. Switching to olanzapine may improve sexual functioning in men and women, but the trial assessing this was small. Further well designed trials and research, which investigate the effects of dose reduction, drug holidays, taking drugs such as Viagra TM, and switching antipsychotic medication, are much needed. This plain language summary (PLS) was written by a consumer contributor, Ben Gray from RETHINK: Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness, Email: [email protected].
+This review indicates that it is unclear whether administering chest radiotherapy within 30 days of beginning chemotherapy or later improves survival. The effect on patients' overall survival is not statistically different, although there is a possibility that the effect is in favour of early chest radiotherapy. The interpretation of the current data is difficult and further research is needed.
+We found 18 trials. They took place in Asia (three trials), Europe (two trials), the Middle East (seven trials), North America (three trials) and South America (three trials). A total of 1005 people took part in these trials and 1131 eyes were studied. Eight trials studied anti-VEGF with another commonly used treatment for diabetic retinopathy (laser), nine studies looked at anti-VEGF at the time of diabetic eye surgery (vitrectomy) and one study investigated use of anti-VEGF in people with diabetic retinopathy having cataract surgery. Most studies followed up the participants for six months but some studies followed up for one year. One study was industry funded, one study was funded by a mixture of government and industry, and three studies were funded by government and non-government organisations. The remainder of the studies did not report a funding source. In one small study, we found that people treated with anti-VEGF plus laser were less likely to lose some vision compared with people treated with laser alone but the estimate was imprecise: around 30% of people treated with laser lost some vision compared with 6% and 24% of people treated with anti-VEGF plus laser. On average, people treated with anti-VEGF had slightly better vision than people not treated with anti-VEGF. They were also less likely to have bleeding in the eye. None of the studies reported on quality of life. One study suggested that injection of anti-VEGF was less painful than having laser treatment. People treated with anti-VEGF before or during diabetic eye surgery (vitrectomy) were less likely to lose some vision compared with people treated with surgery alone, but the estimate was uncertain and it could be that anti-VEGF did not make a difference, or increased the risk of losing vision. On average, people receiving anti-VEGF before or during diabetic eye surgery had slightly better vision than people not treated with anti-VEGF, but again the estimate was uncertain. They were also less likely to have bleeding in the eye. None of the studies reported on quality of life. Side effects were uncommon and there were not enough data to detect a difference between the two groups. The quality of the evidence was low or very low. We judged some of the included trials to be at risk of bias because of lack of masking of treatments and problems with follow-up. Some of the findings were based on too small a numbers of participants. Few studies followed up participants for more than six months.
+This updated review of 13 trials found that oral anticoagulation and antiplatelet drugs were more effective than anticoagulation alone. The addition of antiplatelet drugs to anticoagulants increases the risk of bleeding by about 50%. Low-dose aspirin (less than 100 mg daily) may be associated with the lowest risk of bleeding. However, in general the quality of the included trials tended to be low, possibly reflecting the era when the majority of the trials were conducted (1970s and 1980s when trial methodology was less advanced).
+This review examined the use of a fixed interval of voiding for the management of urinary incontinence in adults. This approach to urinary incontinence is thought to be common in aged care homes for people who require assistance from other people for toileting and continence care. The reviewers found two trials that had evaluated timed voiding. They included 298 elderly women who were living in aged care homes and had reduced cognition and impaired mobility. Reductions in the number of incontinence episodes were reported in each trial. The reviewers found insufficient data for these findings to be combined. Hence, at this point in time, there is not enough evidence on the effects of timed voiding for the management of urinary incontinence.
+We searched a number of databases for relevant studies. From the initial list of 28,654 references, only one study met the inclusion criteria. This study was conducted in 12 antenatal clinics in Zambia. Six intervention clinics implemented HIV testing of women of unknown serostatus and assessment of antiretroviral prophylaxis adherence of HIV positive women. In six control clinics, HIV testing was not performed at labour ward and HIV positive women were informally asked if they took antiretroviral prophylaxis. In all 12 clinics, women were provided with antiretroviral prophylaxis at labour ward if found to be HIV positive and non-adherent to antiretroviral prophylaxis. All children born to HIV positive women were also given antiretroviral prophylaxis. A significant increase in proportion of women and children receiving antiretroviral prophylaxis was observed in the clinics that implemented the PMTCT interventions (of HIV testing and assessment of adherence to antiretroviral prophylaxis) compared to the control clinics. Women and children were more likely to receive antiretroviral prophylaxis at labour wards in the intervention clinics compared to control clinics. Although this one study showed that integrated care improved nevirapine coverage of women and infants more than non-integrated care, the paucity of evidence to confirm or refute this finding more widely suggests more research is urgently needed in other settings to allow a definitive conclusion about the effectiveness of integration of PMTCT interventions with other health services.
+We identified three randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with a total of 50 participants with type 2 diabetes. Among the included studies, the duration of resveratrol supplementation ranged from four to five weeks. Resveratrol as a capsule or Softgel was taken at 10 mg, 150 mg, or 1000 mg daily and was compared to placebo. This evidence is up-to-date as of December 2018. None of the included studies reported on important long-term, patient-relevant outcomes such as death from any cause, diabetes-related death, diabetes-related complications, health-related quality of life, or impact on treatment costs. However, no side effects and no deaths were observed in these short-term studies. No clear changes were observed for indicators of glucose management. We found eight ongoing studies with approximately 800 participants and two studies awaiting assessment, which, when published, could contribute to our findings. The overall certainty of evidence from the included studies was very low, mainly because the number of participants and the number of studies reporting the outcomes were small . Also, the duration of the studies was very short.
+This review compared tacrolimus and cyclosporin used as primary immunosuppression for kidney transplant recipients. Thirty studies (4102 patients) were included. Tacrolimus was shown to be superior to cyclosporin in improving graft survival and preventing acute rejection after kidney transplantation, but increases post-transplant diabetes, neurological and gastrointestinal side effects. There was insufficient information to assess the cost of tacrolimus versus cyclosporin, and there was a general failure to consider global quality of life (QOL) for transplant recipients which may inform our understanding of patient preference and compliance.
+This review included 44 studies that evaluated the impact of school-based interventions focused on increasing physical activity among 36,593 children and adolescents. Participants were between the ages of six and 18 living in Australia, South America, Europe, China, and North America. Duration of interventions ranged from 12 weeks to six years. No two school-based physical activity promotion programs had the same combination of interventions. Furthermore, the duration, frequency, and intensity of interventions varied greatly across studies. Data collection methods for outcomes were reported to be valid and reliable in a little over half of the included studies. There is some evidence that school-based physical activity interventions are effective in increasing duration of physical activity from five to 45 min more per day, reducing time spent watching television from five to 60 min less per day, and increasing maximal oxygen uptake or aerobic capacity, reflecting physical fitness level of an individual. The evidence also suggests that children exposed to school-based physical activity interventions are approximately three times more likely to engage in moderate to vigorous physical activity during the school day than those not exposed. At a minimum, a combination of printed educational materials and changes to the school curriculum that promote physical activity during school hours result in positive effects for these outcomes. School-based interventions are not effective in increasing physical activity rates among adolescents, or in reducing systolic and diastolic blood pressure, blood cholesterol, body mass index, and pulse rate.
+We included eight trials with a total of 356 people. Six of these were published before 1988, were each based in a single centre and used a range of different drugs. These factors made it difficult to combine and analyse the results. We did not find any differences between the two therapies for lung function, symptom scores, side effects or bacteriological outcome measures. We conclude that there is not enough evidence to compare the different therapies. More research is needed, particularly looking at side effects of treatment. Six of the included trials were quite old (published between 1977 and 1988). They did not include many people and had flaws in the way the people taking part were put into the different treatment groups. Overall, the quality of the trials' design was poor.
+This Cochrane systematic review compared landmark techniques versus ultrasound to guide the insertion of a catheter into the large vein in the neck (the internal jugular vein). In 2013 we included in the review 35 studies enrolling 5108 participants (adults and children). These studies were varied, and their quality was moderate at best. We reran the search in August 2014. We will deal with any studies of interest when we update the review. Nevertheless, ultrasound offered some benefits. Using ultrasound reduced the rate of complications (-71%), including severe bruising (-73%) and accidental puncturing of an artery instead of the vein (72%). It also increased success rates, including success rates at the first attempt (+57%) and reduced the time taken to perform the procedure. None of the included studies reported on death or patient-reported outcomes (patient discomfort). Based on available data, we conclude that two-dimensional ultrasound offers improved safety and quality when compared with an anatomical landmark technique, but these findings do not necessarily hold for all users or for patients at high risk of complications. The relative utility of ultrasound when operators are experienced or inexperienced in central line insertion, however, remains unclear for some outcomes. The results for Doppler ultrasound techniques versus an anatomical landmark technique are also uncertain.
+The review authors searched the medical literature up to April 2013, and identified seven relevant medical trials, with a total of 538 participants. The trials were performed in two countries, the USA and Egypt. All the trials had low numbers of participants, and the methods used in them were not of a high quality, which makes potential overestimation of benefits and underestimation of harms more likely. All the trials only included participants with chronic hepatitis C genotype (type) 1 or 4 infection. Outcomes important to people who suffer from this infection include: death from all causes, death from chronic hepatitis C infection, how unwell you feel (morbidity), quality of life, and adverse events caused by the medicines. This review found no information, or very little low quality evidence, about the effects of nitazoxanide on any of these outcomes. Nitazoxanide might have a beneficial effect on virus activity that can be monitored by analysis of blood samples (sustained virological response (SVR) and virological end-of-treatment response (ETR), but this is not certain. Indeed, the review authors could not draw any conclusions about the benefits or harms of nitazoxanide for people with chronic hepatitis C infection. More randomised clinical trials of high methodological quality are needed to establish the effects of nitazoxanide in people with chronic hepatitis C.
+Despite evidence that over 45% of individuals suffering from neuropathic pain take two or more drugs for their pain, we could find only 21 high-quality studies of various different systemic and topical drug combinations. Given the wide possible variety of different drug combinations and the small number of studies, results for neuropathic pain from this review are insufficient to suggest the value of any one specific drug combination. However, the publication of multiple high-quality studies suggesting the superiority of some drug combinations, together with evidence that drug combinations are widely used in clinical practice, underline the importance of conducting more combination studies with improved methodology.
+Sixteen studies (2266 participants) comparing hypothermic machine perfusion with static cold storage were included. The use of hypothermic machine perfusion instead of standard static cold storage reduces the risk of DGF by approximately 23%. Two reports performed economic analysis, in the USA and European settings, and both estimated cost savings with the use of hypothermic machine perfusion. Two studies reported hypothermic machine perfusion prolongs the length of time that donated kidneys survive in the recipient, however we were unable to perform an analysis to confirm this. The effect of HMP on other outcomes (incidence of acute rejection, patient survival, hospital stay, long-term kidney function, duration of DGF) remains uncertain. No completed studies investigating normothermic machine perfusion were identified, but one ongoing study was identified. Compared with standard static cold storage, hypothermic machine perfusion reduces the rate of DGF in kidneys from deceased donors, and likely results in increased survival of the transplanted kidney and overall cost savings. Studies looking at normothermic machine perfusion are required to assess if this results in superior outcomes.
+We identified 29 studies that included participants with stroke or TIA and we found relevant information in nine of them (3339 participants in total). Three had a short follow-up (up to three months) and six had a longer follow-up. Three studies compared marine-derived omega-3 fatty acids to normal care and the remainder used a placebo (dummy). Not all the studies assessed all outcomes. Effects of marine-derived omega-3 fatty acids are unclear for stroke recovery. Only two very small studies reported it, without finding significant differences. One study found less improvement in mood with marine-derived omega-3 fatty acids but the evidence was of low quality. The effect of marine-derived omega-3 fatty acids on vascular-related death, recurrence of stroke, adverse events, and quality of life after having a stroke or TIA is unclear, due to the small number of studies that have assessed them. In the short follow-up, we considered the quality of the evidence very low for recovery, recurrence, frequency of other type of stroke (bleeding or blockage), and adverse events, and low for vascular-related death, quality of life, and mood. For the longer follow-up, the evidence was of very low quality for recovery from stroke, and low quality for vascular-related death, recurrence, adverse events, and mood. Frequency of other type of stroke and quality of life were not reported in the long follow-up.
+To evaluate the effects of various herbal formulations (including single herbs, Chinese proprietary medicines, and mixtures of different herbs) for treating hypertriglyceridaemia, we examined all available randomised controlled trials of Chinese herbal medicines. We identified three studies lasting from four to six weeks and recruiting 170 participants with hypertriglyceridaemia. There were no data on death from any cause, cardiovascular or cerebrovascular events (such as heart attacks or strokes), health-related quality of life, or costs. We found that Chinese herbal medicines used alone or in combination with lipid-lowering drugs or 'life style' changes may have positive effects on reducing the blood levels of triglycerides. No relevant differences in adverse effects occurred and no serious adverse events were noted. On the basis of the current evidence, no definite conclusion is possible especially because of the unclear risk of bias in the included studies and lack of reporting on patient-important long-term outcomes.
+The review includes four studies with 401 children; there were no adult studies. The children were put into groups at random and received either an oral antibiotic continuously as a prevention for at least one year or no antibiotic treatment to prevent infection with Staphylococcus aureus. All children could be given additional antibiotics if their doctor thought they needed them, based on symptoms and germs grown in their respiratory secretions. Studies lasted for a maximum of six years. The review found some evidence that giving regular antibiotics to young children (continued up to six years of age) leads to fewer infections with Staphylococcus aureus. For other outcomes in the review, there was no difference between giving regular antibiotics or not. Since none of the studies lasted longer than six years, we can't draw any conclusions about long-term use. Also, since all studies were in children, we can not comment on the use of these drugs in adults. Future research should look at patterns of antibiotic resistance and survival. All the studies were of variable quality and the quality of the evidence for different outcomes ranged from low to moderate. We judged that the two older studies had a higher risk of bias overall compared to the two newer studies. In particular this was because those taking part in the studies (or their parents or caregivers) would be able to guess which treatment they were receiving, and also one study did not state if anyone had dropped out and if so what the reasons were. Only the newest study seemed to be free of bias, although even here we were not certain if the study results were affected by the way the data were analysed. Further research might change the estimate of the size of the treatment effect and would certainly affect our confidence in the estimated effect.
+We therefore conducted a systematic review of the literature searching key databases for high quality published and unpublished material on the use of adrenaline for emergency treatment; in addition, we contacted experts in this area and the relevant pharmaceutical companies. Our searches retrieved no randomized controlled trials on this subject. We concluded that the use of adrenaline in anaphylaxis is based on tradition and on evidence from fatality series in which most individuals dying from anaphylaxis had not received prompt adrenaline treatment. Adrenaline appears to be life saving when injected promptly, however, there is no evidence from randomized controlled trials for or against the use of adrenaline in the emergency treatment of anaphylaxis. Given the infrequency of anaphylaxis, its unpredictability and the speed of onset of reactions, conducting such trials is fraught with ethical and methodological difficulties.
+We examined the research published up to 07 December 2012. We included 24 randomized controlled trials and 53,247 participants in this review. Four studies assessed the use of oral cholera vaccines to prevent diarrhoea caused by ETEC and eight trials assessed the use of ETEC-specific vaccines to prevent diarrhoea. Seven studies presented data from field trials and four studies presented data from studies where people were artificially infected with ETEC bacteria. Also, 13 trials gave safety and immunological data only. There is currently insufficient evidence to support the use of the oral cholera vaccine Dukoral® to protect travellers against ETEC diarrhoea. Based on a single trial in people travelling from the USA to Mexico, the oral cholera vaccine Dukoral® may have little or no effect in preventing ETEC diarrhoea (one trial, 502 participants, low quality evidence). Two earlier trials, one undertaken in an endemic population in Bangladesh and one undertaken in people travelling from Finland to Morocco, evaluated a precursor of the oral cholera vaccine Dukoral®. Short term protection against ETEC diarrhoea was demonstrated, lasting for around three months (RR 0.43, 95% CI 0.26 to 0.71; two trials, 50,227 participants). However, this vaccine is no longer available. An ETEC-specific, killed whole cell vaccine, which also contains the recombinant cholera toxin B-subunit, was evaluated in people travelling from the USA to Mexico or Guatemala, and from Austria to Latin America, Africa, or Asia. There were no statistically significant differences in ETEC-specific diarrhoea or all-cause diarrhoea (two trials, 799 participants) found and the vaccine was associated with increased vomiting (RR 2.0, 95% CI 1.16 to 3.45; nine trials, 1528 participants). The other ETEC-specific vaccines in development have not yet demonstrated clinically important benefits. Further research is needed to develop safe and effective vaccines to provide both short and long-term protection against ETEC diarrhoea.
+We aimed to identify research studies that tested music interventions combined with standard care for adults with acquired brain injury who were receiving rehabilitation in hospital or community settings. We looked for research that tested the effects of music interventions on walking, moving, communicating, thinking, emotions, pain, and well-being. Interventions included moving to music, singing, listening to music, composing, playing musical instruments, or a combination of these. We identified and included 29 trials involving 775 adult participants. The evidence is current to June 2015. The results suggest that music interventions using rhythm may be beneficial for improving walking in people with stroke, and this may improve quality of life. Music interventions may be beneficial for improving the speed of repetitive arm movements and communication in people with stroke. Music interventions that use a strong beat within music may be more effective than interventions where a strong beat is used without music. Treatment delivered by a trained music therapist might be more effective than treatment delivered by other professionals. Information was insufficient to examine the effects of music interventions on other outcomes. We found no studies that reported on harmful effects. The quality of the research was generally low. We found only one study that we considered as having a low risk of bias. The quality of the evidence for walking speed and stride length was moderate. The quality of the evidence for other aspects of walking was low. The quality of the evidence for the speed of repetitive arm movements was very low, as was the quality of the evidence for overall communication. The quality of the evidence for quality of life was low. Further clinical trials are needed.
+The researchers identified two studies that included a total of 101 participants. One was a high quality study (67 participants) that compared oral methotrexate (12.5 mg/week) to a placebo (a sugar pill or fake medicine). The other study (34 participants) compared oral methotrexate (15 mg/week) against 6-mercaptopurine (an immunosuppressive drug at a dose of 1.5 mg/kg/day) and against 5-aminosalicylic acid (an anti-inflammatory drug at a dose of 3 g/day). In the high quality study, there was no difference between the methotrexate and placebo treatment groups for the number of people who achieved remission and were able to stop taking steroids. This suggests that, when used at this low dose (12.5 mg/week), methotrexate does not produce remission from ulcerative colitis. However, this result is uncertain because of the small number of people who were assessed. The other, smaller study showed no differences between methotrexate and the other treatments in the proportion of participants who experienced remission and were able to stop taking steroids. This result is also uncertain due to poor study design and the low number of participants. The side effects reported in the two studies included leucopenia (a decrease in the number of white blood cells), migraine, rash, nausea and dyspepsia (indigestion), mild alopecia (hair loss), mild increase in levels of an enzyme found in the liver (aspartate aminotransferase), a collection of pus in the abdominal tissue (peritoneal abscess), abnormally low levels of the protein albumin in the blood (hypoalbuminemia), and pneumonia. At present, the results from medical trials do not support the use of low dose oral methotrexate (12.5 mg to 15 mg/week) for the production of remission in active ulcerative colitis. It is not known whether a higher dose of oral methotrexate, or giving methotrexate by a different route (e.g. by injection), would increase the likelihood of remission. In future, researchers should consider organising a study with a larger number of participants who receive a higher dose of oral methotrexate. Currently, there are two large studies being run that compare a higher dose of methotrexate – given by injection – with placebo in people with active ulcerative colitis (the METEOR and MERIT-UC studies). The results of these studies may resolve the uncertainty surrounding the use of methotrexate for the treatment of active ulcerative colitis.
+This review found that there is not enough evidence from trials about the effects of amantadine for people with dyskinesia in Parkinson's disease. Adverse effects in trials so far have included confusion, worsening of hallucinations, the re-emergence of palpitations, nausea, dry mouth, swelling of feet and constipation.
+We did computer searches for relevant studies and looked at the reference lists of study reports to identify more studies. We found nine studies of moderate to low quality. Three studies on contraceptive counselling and referrals by community workers showed an increase in use of the copper IUD. Two studies on antenatal contraceptive counselling and one study on postnatal couple counselling, with provision of an information leaflet before being discharged from the maternity ward, also showed an increase in use of the copper IUD. A study on postnatal home visits and two studies on enhanced postabortion contraceptive counselling did not show an increase in use of the copper IUD. More high-quality research is needed to look at the longer-term effectiveness of interventions to improve use of the copper IUD.
+We searched for relevant trials up to December 2013. The studies brought together trial data from all over the world with 26 trials (34 trial comparisons) and 8447 patients in the first meta-analysis (surgery versus surgery plus adjuvant chemotherapy); and 12 trials (13 trial comparisons) and 2660 patients in the second meta-analysis (surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy). Trials were carried out between 1979 and 2003. Results found that people with non-small cell lung cancer that had surgery followed by chemotherapy (with or without radiotherapy), lived longer than those who had surgery without chemotherapy (with or without radiotherapy).  After five years, 64 out of every 100 patients who were given chemotherapy after surgery were alive compared to 60 patients out of every 100 who just had surgery. For those who also received radiotherapy, after five years, 33 out of every 100 patients who received chemotherapy, surgery and radiotherapy were alive compared to 29 out of every 100 patients who received surgery and radiotherapy. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable.  In both studies, there was little variation in the effect of chemotherapy according to the type of chemotherapy given, other trial characteristics, or by the type of patient included in the trial. These systematic reviews and meta-analyses use individual participant data, which is considered the gold standard of this type of review. We included all eligible trials if possible, no matter what language they were published in or whether they were published or not.  The first meta-analysis (surgery versus surgery plus adjuvant chemotherapy) included 92% of all patients in eligible trials and the second meta-analysis (surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy) included 86% of all patients in eligible trials. We are confident that further research is unlikely to change the findings. The studies were well designed and conducted, address the review question, and the effects are consistent across trials. The impact of any data we have not been able to include in our analyses is small.
+We searched for studies up to January 2017. We found five studies, and they investigated 278 people. Most people included in the studies were women, who were around 50 years of age, and reported a mixture of chronic pain conditions (e.g. headache, back pain, muscle pain). The studies included acupuncture, mindfulness, and cognitive behavioral therapy as strategies to decrease the amount of opioids taken by adults with chronic pain. No conclusions can be drawn from this small amount of information. Therefore, it is not clear whether these treatments decrease the amount of opioids in adults with chronic pain (primary outcome) or reduce pain intensity, physical ability or mood (secondary outcomes). Three studies did include negative effects of their treatment, and two reported that the participants did not have anything negative happen to them because of the trial they were in. Non-randomised studies, not included in this review, do indicate that for many people intensive rehabilitation packages may bring about major reduction in opioid use. Reducing prescribed opioid use in chronic non-cancer pain is an important topic in need of more systematic research. We were not able to judge the quality of evidence included in this review because the studies were so different and could not be combined.
+We identified one randomised controlled clinical trial (RCT) of the non-surgical treatment of 90 people with LM: 44 were treated with imiquimod cream plus tazarotene gel, and 46 were treated with imiquimod cream for 3 months; these interventions were followed by staged excision after 2 months. We did not find any RCTs of surgical treatments. Of those treated with imiquimod and tazarotene, 66% had a complete response at 5 months compared with 59% of those treated with imiquimod alone. The addition of tazarotene to imiquimod did not lead to a clinically better response, and the people in this group had higher inflammation. There were more dropouts due to adverse effects in this group. The quality of evidence is poor. With regard to the treatment of MIS, surgical interventions that aim to excise the tumour so that none of the tumour cells are in the margin are the most recommended interventions in non-selected cases. The evidence does not support the use of non-surgical interventions in selected cases (i.e., in elderly people with contraindications to surgical interventions). However, clinical centres may consider it where there is experience of this treatment and where close and adequate follow up can be undertaken. With regard to the treatment of LM, surgical interventions remain the most recommended available treatment. The evidence does not support the use of non-surgical interventions, such as imiquimod, as a single therapy in non-selected cases. It may be considered only in selected cases and in clinical centres with experience. The evidence so far does not support the use of imiquimod as a neoadjuvant (i.e., before surgery) therapy but warrants further investigation, in order to evaluate if use after surgery can minimise recurrence and if use before surgery of large lesions or difficult sites can help to achieve smaller surgical excisions. The evidence does not support addition of tazarotene to imiquimod as neoadjuvant therapy.
+We identified 10 randomised controlled trials with a total of 2361 participants that evaluated compression therapy (current until March 2017). We combined five trials to assess our main outcome - PTS. We found that people with DVT who wear elastic compression stockings are less likely to develop PTS, and that compression did not lead to reduced incidence of severe PTS. We found no clear differences in occurrence of pulmonary embolism (blockage of the artery in the lung) nor in reports of recurrent DVT. Compression in the acute phase of DVT compared with "no compression" treatment did not significantly lower PTS incidence. Thigh-length stockings did not provide better protection against development of PTS than knee-length stockings. One trial reported that wearing compression stockings for two years seemed to be superior to wearing them for one year in terms of PTS incidence. Compression treatment did not seem to improve quality of life, except during the first nine days after DVT, but we could draw no real conclusions regarding this outcome. Side effects included itching, erythema, and other forms of allergic reaction. The study investigators reported no serious adverse events and indicated that compliance with use of compression stockings was generally high but varied across studies. Although studies show a reduction in the number of people developing PTS, the quality of evidence is low because of considerable differences between studies and lack of or unclear risk of blinding due to clinical assessment scores. Overall, the included studies were of poor methodological quality.
+This systematic review of randomised controlled trials (RCTs) of pharmacotherapy of anxiety disorders in children and adolescents identified 22 short-term (<= 16 weeks) randomised controlled trials which were eligible for inclusion (2519 participants). Treatment response was significantly greater after treatment with medication (58.1%) than with placebo (31.5%) in 14 trials. Medication was more effective than placebo in reducing overall symptom severity across all of the anxiety disorders (number of studies (N) = 9). The greatest number of trials were for obsessive compulsive disorder (OCD), for which treatment efficacy in reducing symptom severity was also observed . The greatest number of trials showing efficacy to date have used the selective serotonin reuptake inhibitors (SSRIs). No controlled evidence could be found for the effectiveness of benzodiazepines, despite their continued prescription for paediatric anxiety disorders. Medication was less well tolerated than placebo, as indicated by the significant proportion of children and adolescents who dropped out due to adverse effects during the short term trials. Furthermore, while few incidences of suicidal behaviour/ideation in the included trials were attributed to study medication, it is important to be aware of the need for careful monitoring after initiation of SSRIs in treating this population. In conclusion, medication should be considered as part of the treatment of paediatric anxiety disorders over the short-term. Additional research into the optimal dose and duration of medication treatment, as well as the effects of age on the efficacy and tolerability of medication is warranted.
+We included eight studies in the review reporting results from a total of 96 people with cystic fibrosis. All the studies were very different and some looked at multiple treatments compared to no treatment. One study looked at autogenic drainage, six considered conventional chest physiotherapy, three considered oscillating positive expiratory pressure, seven considered positive expiratory pressure and one considered high pressure positive expiratory pressure. We could not combine the results to analyse them statistically. Summarising the findings of these eight studies, we found that methods of clearing the airways have short-term benefits for moving mucus. Three studies measured sputum which had been coughed up and found those people using chest physiotherapy coughed up more sputum; four studies measured radioactive tracer clearance and found increased clearance with chest physiotherapy. Only one study reported an improvement in lung function in some of the treatment groups; but three other studies who reported this outcome did not find any significant effect from chest physiotherapy. At present there is no clear evidence of long-term effects in chest clearance, quality of life or survival with chest physiotherapy. Most of the included studies had some design problems which may affect confidence in the results. In just under half of the studies it was not clear as to whether all of the results were reported. In physiotherapy studies the person and their physiotherapist will know which treatment they are receiving and this may affect some of the findings. Half the studies looked at amount of sputum coughed up and lung function testing, with a quarter asking the person's views on the treatment and these results may have been affected by being aware of the treatment. In all of the studies it was not clear if the person was experienced in carrying out the treatment. This may affect how well they were able to do the treatment which could affect confidence in the results.
+We searched electronic databases and other sources up to June 2015 and found five relevant studies that reported the results for 368 adults with PFPS. Participants were recruited from health clinics in three studies and were military trainees in the other two studies. All five studies were small and at high risk of bias, which means that their findings may not be reliable. The studies covered three different types of comparison: knee orthosis and exercises versus exercises alone; one type of orthosis versus another; and knee orthosis versus exercises. No study assessed the mode of knee orthosis use, such as whether the orthosis was worn all day or only during physical activity. All five trials compared a knee orthosis (either sleeve, brace or strap) plus exercise versus exercise alone. These provided very low quality evidence that wearing a knee orthosis made no difference to knee pain (data from three studies) and function (data from two studies). None of the three studies reported on quality of life, resource use or participant satisfaction. One study reported that both participants quitting military training due to knee pain were allocated a knee orthosis. One poorly reported study found over a third of knees had discomfort or skin abrasion in those given a knee sleeve. Three studies provided very low quality evidence on single comparisons of different types of knee orthoses: a knee brace versus a knee sleeve (63 participants), a patella strap with a knee sleeve (31 participants), and a knee sleeve with a patellar ring versus a knee sleeve only (44 knees). None of three studies found an important difference between the two types of knee orthosis in knee pain. One study found no important difference in function between a knee brace and a knee sleeve. None of the three studies reported on quality of life, resource use or participant satisfaction. One study comparing a patella strap with a knee sleeve reported that both participants quitting military training due to knee pain were allocated a knee sleeve. One poorly reported study found three times as many knees with discomfort or skin abrasion in those given knee sleeves with a patella ring than those given knee sleeves only. One study (66 participants) compared a knee orthosis (knee brace) with exercise. It provided very low quality evidence of no clinically important difference between the two intervention groups in pain or knee function. It did not report on other outcomes including complications. Overall, we found a lack of evidence to inform on the use of knee orthoses for treating PFPS. Our review found very low quality evidence from trials testing different knee orthoses (knee brace, sleeve and strap) that using a knee orthosis may not reduce knee pain or improve knee function in the short term (under three months) in adults who were also undergoing an exercise programme for treating PFPS. These findings point to the need for good-quality clinically-relevant research to inform on the use of commonly-available knee orthoses for treating PFPS.
+Several non-randomised studies have reported differences in the psychological benefits, aesthetics and complication rates based on the timing of reconstruction. This review sought to compare the effects of the timing of reconstruction on morbidity and mortality, patient satisfaction and psychosocial well-being. Only one eligible randomised controlled trial (RCT) was found, which involved 64 women. However, because a substantial number of participants in the study chose not to undergo delayed reconstruction, it was not possible to make a fair comparison of the mixed group with those participants who underwent immediate reconstruction. Methodological flaws and a high risk of bias also diminished the quality of evidence found in the RCT. Since we have only identified one RCT in this area, an updated version of this review will evaluate other study designs specifically good quality cohort and case-control studies. Further research should aim to provide reliable evidence for people to make informed decisions as to the best and most appropriate timing of breast reconstruction following surgery for breast cancer.
+The trial finding suggested that compression stockings did reduce symptoms associated with CVI including aching of the legs, discomfort, fatigue, swelling and tiredness. However, this evidence was from a very small study. Due to the extremely limited number of trials available, we could not assess the effectiveness of other non-pharmacological interventions in the prevention of this condition. Nor could we ascertain if any intervention had an effect on quality of life or an economic impact such as reducing the number of days of sick leave or work disability. Further research that looks at a broad range of proposed interventions in a clearly defined standing worker population is required.
+This review includes randomised controlled trials, which lasted at least 12 weeks. Participants were between 37 to 54 years old on average. The evidence is current up to 30 July 2015. We included five trials (435 participants), one of which had two treatment arms. All five trials investigated the effects of eating nuts. No studies were found which investigated the effect of giving advice to eat more nuts. None of the studies reported on deaths or cardiovascular events. None of the results show a clear effect on total cholesterol levels and blood pressure. One study reported one case of an allergic reaction to nuts. Three studies reported no significant weight gain with increased nut consumption. No other adverse events were reported. All included trials are small, with 60 to 100 participants, and have a high level of variation (heterogeneity). Therefore the results should be interpreted with caution. Overall we regarded the included trials as being at unclear risk of bias.
+Ten randomised trials involving 1139 women met the inclusion criteria for the review. Nine studies compared heparin (alone or in combination with dipyridamole) with no treatment; and one compared triazolopyrimidine with placebo. The most commonly recognised side effect for women related to this treatment was mild skin bruising. To date, important information about serious adverse infant and long-term childhood outcomes with using anti-clotting medications is unavailable. Further research is required.
+We found six studies with a combined total of 3436 patients (until March 2017). Five studies compared treatment with placebo, and one study compared one type of treatment with another. Three of the five studies that used a placebo used warfarin, and two used aspirin. Combining results of the five studies showed no clear difference in the rate of further clots between patients treated with an anticoagulant and those treated with a placebo, and no clear difference in the numbers of deaths, bleeding incidents, or adverse effects such as stroke or heart attack. One study showed that oral treatment with the anticoagulant rivaroxaban was associated with fewer clots than aspirin. There was no evidence of a difference in major and non-major bleeding events between rivaroxaban and aspirin. Data on deaths and deaths related to clots in the lungs, stroke, and heart attack were not yet available for participants relevant to this review and will be incorporated in a future version of the review. The quality of the evidence provided by studies included in this review ranged from low to moderate because a small number of studies with few events were included. This review found that trials are too few to show whether extended treatment is safe and effective in preventing further blood clots after three months' treatment. Further good-quality and large-scale studies are required.
+Studies have claimed the beneficial role of biliary decompression, which can be performed via endoscopic retrograde cholangiopancreaticography (ERCP) with stent insertion pre-surgically. The review found that pre-surgical biliary stenting via ERCP did not improve the morbidity and mortality in patients with pancreatico-biliary malignancy. Further evidence about its efficiency is needed.
+The evidence was current up to 13 February 2013. We found six relevant studies, five of which were large observational studies from the US with a comparison group and with study durations from two to 11 years, and one was a much smaller 12 week study from Haiti. There were over 1.5 million participants in the studies. Information for these studies was taken from American insurance databases (Medicare) and from hospital records. The small study was based on emergency medical care after the 2008 hurricanes in Haiti. Most studies stated that there was no difference in the number of people who died when given anaesthetic by either a nurse anaesthetist or a medically qualified anaesthetist. One study stated that there was a lower rate of death for nurse anaesthetists compared to medically qualified anaesthetists. One study stated that the risk of death was lower for nurse anaesthetists compared to those being supervised by an anaesthetist or working within an anaesthetic team, whilst another stated the risk of death was higher compared to a supervised or team approach. Other studies gave varied results. Similarly, there were variations between studies for the rates of complications for patients depending on their anaesthetic provider. Much of the data came from large databases, which may have contained inaccuracies in reporting. There may also be important differences between patients that might account for variation in study results, for example, whether patients who were more ill were treated by a medically qualified anaesthetist, or whether nurse anaesthetists worked in hospitals that had fewer resources. Several of the studies had allowed for these potential differences in their analysis, however it was unclear to us whether this had been done sufficiently well to allow us to be confident about the results. There was also potential confounding from the funding sources for some of these studies. As none of the data were of sufficiently high quality and the studies presented inconsistent findings, we concluded that it was not possible to say whether there were any differences in care between medically qualified anaesthetists and nurse anaesthetists from the available evidence.
+We found seven studies from our search of 19 databases. All together, the studies included 1924 elderly participants and 740 people (such as carers or nursing home staff) with whom they interact. These studies described methods of preventing or reducing elder abuse with elderly people. The studies included programs and strategies that took place in many different settings (home, community, institutions) although only in high-income countries. The programs and strategies identified included methods to increase detection in clinical practice and community settings, victim support, increasing awareness of elder abuse and delivering training programs aimed at building skills in care providers. Most studies described changes in knowledge and attitudes, with very few measuring the occurrence or reoccurrence of abuse. The study durations ranged from six to 24 months. The included studies suggest it is uncertain whether targeted educational interventions improve the knowledge of health and allied professionals and caregivers about elder abuse. It is unclear whether any improved knowledge actually leads to changes in the way they behave thereafter, and whether this leads to the elderly being abused less. Similarily, supporting and educating elderly victims of abuse appears to lead to more reporting of abuse, however it is unclear if the higher reporting meant more abuse occurred or a greater willingness to report the abuse as it occurred. None of the studies reported any unintended outcomes of these approaches. Most of the evidence was low or very low quality (we cannot assume the findings of these studies are true) and limits our understanding of what strategies or programs work best to decrease or prevent elder abuse. Many of the studies were unclear in the design, too small in size or not similar enough in their findings to have full confidence in the findings.
+This review found that a single subcutaneous dose was effective in relieving migraine headache pain and associated symptoms of nausea, sensitivity to light, and sensitivity to sound. Pain was reduced from moderate or severe to no pain by two hours in almost 6 in 10 people (59%) taking sumatriptan 6 mg, compared with about 1 in 7 (15%) taking placebo, and reduced from moderate or severe to no worse than mild pain by two hours in almost 8 in 10 people (79%) taking sumatriptan compared with about 3 in 10 (31%) taking placebo. Subcutaneous sumatriptan was fast-acting, and the majority of people experiencing pain relief had done so by one hour. About 3 in 10 (31%) people had freedom from pain at two hours which was sustained during the 24 hours postdose without the use of rescue medication, compared with about 1 in 7 (15%) with placebo. In addition to relieving headache pain, sumatriptan also relieved symptoms of nausea and sensitivity to light and sound by two hours in about half of those who took it, compared with about one-third of those taking placebo. Adverse events, most of which were of short duration and mild or moderate in severity, were more frequent with sumatriptan than with placebo.
+The purpose of this review was to evaluate calcitonin as a means of preventing bone loss with corticosteroid therapy. Nine randomized controlled trials were included in the review, with 221 patients randomized to calcitonin and 220 to placebo. The results showed that calcitonin prevents bone loss at the spine and forearm by about 3% after the first year of therapy. There was no effect on bone loss at the hip. Calcitonin was not statistically different from placebo at preventing fractures of the spine and long bones, such as hip fractures. Calcitonin was associated with four times the side effects of placebo, and these were mostly nausea and facial flushing.
+For the first 14 weeks of pregnancy, the evidence supports the use of the double test of two blood markers; pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotrophin (βhCG), in combination with the mother's age. This test detects around seven out of every 10 (68%) pregnancies affected by Down's. It is common practice to offer amniocentesis or CVS to women with a high risk test result. About one in 20 women (5%) having this test will have a ‘high risk’ result but most of these women will not be carrying a baby with Down’s. We found for tests in the first 14 weeks of pregnancy, there is little evidence to support the use of serum tests made up of more than two blood markers.Other important information to considerThe blood tests themselves have no adverse effects for the woman, over and above the risks of a routine blood test. However some women who have a ‘high risk’ screening test result, and are given amniocentesis or CVS have a risk of miscarrying a baby unaffected by Down’s. Parents will need to weigh up this risk when deciding whether or not to have an amniocentesis or CVS following a ‘high risk’ screening test result.
+We searched for studies up to 1st August 2014. A total of 32 studies were part of this review and included 6,075 patients in total. The studies were carried out in many different countries throughout Europe, Asia and North America. The studies were conducted between 1981 and 2014. The review showed that patients who received platinum-based chemotherapy were not any more likely to be alive at 6 months, 12 months and 24 months after treatment compared with patients who received non-platinum-based chemotherapy. Platinum-based chemotherapy, however, showed higher rates of complete tumour response (the complete disappearance of tumours, at least for a period of time after treatment) compared to non-platinum-based chemotherapy. Platinum-based chemotherapy also caused some more side effects, including nausea and vomiting, and low platelets. Only four studies looked at quality of life but because they each used different methods to measure the effects, their results could not be combined. However, in each study there was no difference in the quality of life between the platinum-based chemotherapy group and the non-platinum-based chemotherapy group.
+CBT is significantly more effective than no therapy in reducing symptoms of anxiety in children and young people. No clear evidence indicates that one way of providing CBT is more effective than another (e.g. in a group, individually, with parents). CBT is no more effective than other 'active therapies' such as self-help books. The small number of studies meant the review authors could not compare CBT with medication. Only four studies looked at longer-term outcomes after CBT. No clear evidence showed maintained improvement in symptoms of anxiety among children and young people. The review authors recommend that future research should look in greater detail at what makes CBT work best for children and young people, how CBT can be provided in the most cost-effective way, and how CBT can be adapted for different age groups.
+we included randomised controlled trials that compared a standard antibiotic regimen versus the same regimen with an antibiotic directed at gram-positive bacteria. Overall, 14 randomised controlled trials were included with 2782 patients or episodes of infection. The antibiotics were given to cancer patients with neutropenia and fever as first-line treatment (12 trials) or for recurrent fever (two trials). In 9/14 of the trials the trial received funding from the industry. mortality did not differ between patients groups. Antibiotic treatment was more frequently modified among patients who did not initially receive specific antibiotics against gram-positive bacteria, but overall treatment failures were not different. We attempted to examine the durations of fever and hospital stay, but these were not consistently reported. The addition of specific antibiotics against gram-positive bacteria resulted in more adverse events, mainly rash. We conclude that antibiotic treatment directed against resistant gram-positive bacteria can await identification of specific bacteria and need not be given routinely prior to bacterial identification. overall, the quality of the evidence was low to very low but was based on randomised controlled trials, most of which were at low risk of bias. A limitation of the results for mortality was that all-cause mortality was not reported and could not be obtained in 6/14 of the studies. The trials did not examine specific circumstances that might mandate empirical use of antibiotics against gram-positive bacteria and thus the evidence is relevant to cancer patients with fever, without low blood pressure, or a focus of infection that might be caused by gram-positive bacteria.
+We did not find any trials of antifibrinolytic medicine for preventing bleeding after minor oral surgery or dental extractions in people using DOACs. This review includes four trials (253 participants) in people continuously treated with VKAs during minor oral surgery or dental extractions. The earliest included trial was published in 1989 and the most recent one in 2015. The mean age of all participants was 60 years. The follow-up time in all trials was seven days. Overall, the included trials showed a reduction in the number of bleeds after dental extraction when using tranexamic acid solution in the mouth. Combining the results of the separate trials it appeared that antifibrinolytic medication reduces the bleeding rate after dental extractions by 25% when compared to placebo ('dummy' treatment). However, there was no difference in bleeding rate between people treated with tranexamic acid and those treated with standard care (e.g. gauze compression or stitches). Side effects of the antifibrinolytic medication rarely occurred and did not lead to individuals discontinuing tranexamic acid treatment. No evidence was found for people being treated with DOACs. It could, however, be argued that, if antifibrinolytic medicine is effective in people on continuous treatment with VKAs, it might also work for people receiving other comparable anticoagulant drugs. In relation to the review's two primary outcomes of number of postoperative bleeds and side effects of therapy, we judged there to be moderate-quality evidence. In the two trials comparing tranexamic acid with placebo, the risk of bias, in relation to trial design, was considered to be low, in the two trials comparing tranexamic acid to standard care (gelatin sponge and sutures; or dry gauze compression) the risk of bias was considered to be moderate. This was mainly due to the lack of blinding (a way of making sure that the people involved in the trial do not know which trial arm they are assigned to) and inadequate allocation concealment (using the play of chance to assign participants to comparison groups to prevent selection bias) in two of these trials. There were differences between the trials with regards to different standard care treatments.
+We reviewed the evidence for the effectiveness and safety of antidepressants for the treatment of agitation and psychosis in older adults with dementia. We classified antidepressants based on their mechanism of action and included studies that compared antidepressants to treatment with either placebo or other medications frequently used to manage these symptoms. A total of nine studies (including 692 individuals) were identified, four comparing selective serotonin reuptake inhibitors (SSRIs) to placebo, three comparing SSRIs to typical antipsychotics, and one study comparing SSRIs to atypical antipsychotics. One study compared the antidepressant trazodone to placebo, and two compared trazodone to haloperidol. Most of the studies included in the review were relatively small and of uncertain risk of bias due to methodological issues. The SSRIs sertraline and citalopram were associated with a modest reduction in symptoms of agitation and psychosis when compared to placebo in two studies. There were few other statistically significant differences in changes in agitation or psychosis or in most measures of medication tolerability for SSRIs or trazodone when compared to placebo or the antipsychotic haloperidol. We conclude that there is some evidence to support the use of certain antidepressants for agitation and psychosis in dementia and further studies are required to determine the effectiveness and safety of SSRIs and trazodone in managing these symptoms.
+The evidence is current to May 2017. We included experimental and selected non-experimental studies of UCTs in people of all ages in LMICs. We included studies that compared participants who received a UCT with those who received no UCT. We looked for studies that examined health services use and health outcomes. We found 21 studies (16 experimental and 5 non-experimental ones) with 1,092,877 participants (36,068 children and 1,056,809 adults) and 31,865 households in Africa, the Americas and South-East Asia. The UCTs were government programmes or research experiments. Most studies were funded by national governments and/or international organisations. We use the words 'probably' to indicate moderate-quality evidence, 'may/maybe' for low-quality evidence, and 'uncertain' for very low-quality evidence. A UCT may not impact the likelihood of having used any health service in the previous 1 to 12 months. UCTs probably led to a clinically meaningful, very large reduction in the risk of having had any illness in the previous two weeks to three months. They may increase the likelihood of having had secure access to food over the previous month. They may also increase the average number of different food groups consumed in the household over the previous week. Despite several studies providing relevant evidence, the effects of UCTs on the likelihood of stunting and on depression levels remain uncertain. No study estimated effects on dying. UCTs probably led to a clinically meaningful, moderate increase in the likelihood of currently attending school. The evidence was uncertain for whether UCTs impacted livestock ownership, extreme poverty, participation in child labour, adult employment and parenting quality. UCTs may increase the amount of money spent on health care. The effects of UCTs on differences in health were very uncertain. We did not identify any harms from UCTs. Three experimental studies reported evidence on the impact of a UCT compared with a CCT on the likelihood of having used any health services, the likelihood of having had any illness or the average number of food groups consumed in the household, but evidence was limited to one study per outcome and was very uncertain for all three. Of the seven prioritised primary outcomes, the body of evidence for one outcome was of moderate quality, for three outcomes of low quality, for two outcomes of very low quality, and for one outcome, there was no evidence at all. This body of evidence suggests that unconditional cash transfer (UCTs) may not impact health services use among children and adults in LMICs. UCTs probably or may improve some health outcomes (i.e. the likelihood of having had any illness, the likelihood of having secure access to food, and diversity in one's diet), one social determinant of health (i.e. the likelihood of attending school), and healthcare expenditure. The evidence on the health effects of UCTs compared with those of CCTs is uncertain.
+This review aims to compare CMHTs with inpatient care, hospital-based out-patient care or day hospital (standard care) for people living in the community with a serious mental health problem. Three randomised control trials were found that fulfilled these criteria.  They included a total of 587 people, took place in urban areas of the UK and lasted from three months to one year. In the two studies that recorded it, a total of 52 people from 253 left the study early, though there was no significant difference in numbers between CMHT and control. Deaths in each study were recorded (suicide, suspicious circumstances and physical ill-health), and although there were no significant differences between the two groups, those in the CMHT group were consistently lower than in standard care.  People in CMHTs were also significantly less likely to be admitted to hospital during the period of the study, and were less likely to use social services. However, there was no significant difference between the groups in the use of accident and emergency services, general hospital services and primary care (family doctors). One study looked at satisfaction with care and found those in CMHTs were more satisfied with their care than the standard care group. In the UK and other Western world countries, the move to CMHT has happened despite the limited evidence given above, therefore improving the evidence base is difficult.  This should be borne in mind when comparing CMHTs with more specialised services such as early intervention or crisis resolution.  (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org)
+This review assessed the efficacy of single-dose dihydrocodeine in adults with moderate/severe postoperative pain using information from randomised placebo controlled trials. There was a lack of data that could be included in the analyses; all assessed the oral form of the drug and none assessed dihydrocodeine 60 mg. The results were not robust. The implication was that single-dose oral dihydrocodeine 30 mg was more effective than placebo, but was inferior to ibuprofen 400 mg. Dizziness, drowsiness and confusion were commonly reported.
+The review included four small studies with a total of 86 participants. Each study investigated a different treatment. These were a drug treatment (modafinil) compared to placebo, breathing exercises compared to sham (inactive) breathing exercises, exercises with weights compared to usual care, and magnetic brain stimulation compared to sham rTMS. We are very uncertain about the effects of modafinil, breathing exercises, exercises with weights, or magnetic brain stimulation on fatigue in people with ALS/MND, as the evidence was very low quality. It was often unclear whether studies were adequately designed and performed, as trial reports often lacked details. The results of these small studies were not precise. Three participants stopped taking modafinil because of side effects: headache in two, and chest tightness in one; participants also reported anxiety, nausea, dizziness, and sialorrhoea (inability to control oral secretions). We need more research on effective treatments for fatigue in ALS/MND. The searches are up to date to September 2017.
+We searched reference lists, biomedical databases (Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Web of Science, PubMed Publsiher, and Google Scholar), and trial registries up to 13 May 2015. Additional searches were run in September 2017 prior to publication, and they are listed in the 'Studies awaiting assessment' section. We identified 41 randomized controlled trials (RCTs) that met our inclusion criteria for inclusion in the review, as well as 49 ongoing studies. This review and meta-analysis shows that people who receive more chemotherapeutic or targeted therapeutic agents live longer and with less disease progression than people who receive best supportive care or less therapy. The only individual agent that more than one study found to improve survival was ramucirumab. We found severe treatment-associated toxicities (grade 3 or above) more frequently in the arms with an additional chemotherapy or targeted therapy agent. However, there is no evidence that palliative chemotherapy and/or targeted therapy decreases quality of life. Our meta-analysis indicates that chemotherapy and targeted therapy are effective palliative treatments for people with esophageal and gastroesophageal junction cancer. The evidence that more chemotherapeutic or targeted therapeutic agents increase survival is of high quality, as is the evidence for improved survival compared to best supportive care. The evidence for the increased occurrence of severe treatment-related toxicities is of very low quality, while the evidence showing no decrease in quality of life is also low quality.
+The conclusion is based on limited data from two small studies. The larger of the studies, conducted in 73 patients with Alzheimer's disease, showed no beneficial effect of trazodone at all. A smaller cross-over study in patients with frontal lobe dementia showed a trend for reduction in some symptoms in the first study period. Larger, longer studies are needed to explore the efficacy, effectiveness and safety of trazodone.
+Based on the results of this review, which included eight studies involving 1007 participants, there is currently not enough information available to help us work out what services might be best for informal caregivers of stroke survivors. However, another 11 studies are currently underway, which may help us find out what works best.
+We looked for studies that compared a group of people given any type or dose of antibiotic with a group of people not given an antibiotic for an exacerbation. We included only studies in which it was decided by chance who would get an antibiotic. We included studies in adults and children carried out at any time and anywhere in the world. We found six studies that included 681 adults and children with asthma. Two of these studies were carried out over 35 years ago. Overall, we found a small amount of evidence suggesting that antibiotics may improve symptoms and breathing test results compared with no antibiotic. We are not very sure about these results because only a small number of studies and people were included in our review. One of our primary outcomes - admission to intensive care unit/high dependence unit (ICU/HDU) - was not reported. We also cannot be sure if people given antibiotics have more or fewer adverse events (side effects). Only 10 people (5 given antibiotics and 5 given placebo/no antibiotic) out of 502 had a serious adverse event. We did not find much evidence about other important outcomes, such as admission to hospital or another exacerbation during the study follow-up period. The most recent study found it difficult to recruit people with asthma because so many of them had already been given an antibiotic and so could not take part. Overall, we have low confidence in the evidence presented in this review. We think it is possible that some studies of antibiotics for asthma exacerbations have been carried out but not published because we were able to find so few studies about such an important question. We were also worried about how well study findings apply to all people with asthma attacks because most of the studies that we found recruited only people in hospitals and emergency departments. Also, two of the studies were old, and asthma treatment has changed a lot in 30 years. Because we found only a few studies, in some cases we cannot tell if antibiotics are better than, worse than, or the same as no antibiotic. Finally, we had some concerns about the ways in which studies were carried out, for example, in one study both patients and study staff knew who was getting an antibiotic and who was not; this might have affected how patients or staff behaved. We found very limited evidence that antibiotics may help people having asthma attacks, and we are still very unsure. In particular, we did not find much information about important outcomes such as hospital admissions or side effects. However, serious side effects were very rare in the studies that we found.
+This review found that, despite limited research, there is some evidence that guidelines can improve care and that professional roles can be substituted effectively, for instance a nurse can perform the function of a physician in certain circumstances. Such interventions offer the possibility of reduced costs but further research is needed in all areas of this topic.
+We identified three studies, involving a total of 120 participants, comparing packed red blood cells stored for ≥ 21 days versus < 21 days. The results of the studies for the outcome death from any cause were uncertain due to the small number of participants who contributed information. We could not exclude an effect on death with either longer or shorter storage. None of the trials considered the other outcomes of interest in this review, namely transfusion-related acute lung injury, postoperative infections, and adverse events. The safety profiles of the two approaches are unknown. The level of confidence in the results of this review is very low. The studies have limitations in the way they were designed and executed. Moreover, the limited number of people included in the studies led to imprecise results. We are aware of four large ongoing trials in this area which will help us to better understand the effects of storage on red blood cells in relation to outcomes for patients.
+A review update of the research of the strategies of partner notification in people with STI, including human immunodeficiency virus (HIV) infection was conducted by researchers in the Cochrane Collaboration. After searching for all relevant studies, they found 26 studies. This review covers four main PN strategies: 1) Patient referral means that the patient tells their sexual partners that they need to be treated, either with (enhanced) or without (simple) additional support to enhance outcomes. 2) Expedited partner therapy means that the patient delivers medication or a prescription for medication to their partner(s) without the need for a medical examination of the partner. 3) Provider referral means that health service personnel notify the partners. 4) Contract referral means that the patient is encouraged to notify partners but health service personnel will contact them if they do not visit the health service by a certain date. The 26 trials in this review included 17,578 participants. Five trials were conducted in developing countries and only two trials were performed among HIV-positive patients. Expedited partner therapy was more successful than simple patient referral in reducing repeat infection in patients with gonorrhoea, chlamydia or non-gonococcal urethritis (six trials). Expedited partner therapy and enhanced patient referral resulted in similar levels of repeat infection (three trials). Evidence about the effects of home sampling, where patients with chlamydia received a sample kit for the partner, was inconsistent (three trials). There were too few trials to allow consistent conclusions about the relative effects of provider, contract or other patient referral methods for different STIs. More studies need to be performed on HIV and syphilis and harms need to be measured and reported.
+The evidence was based on 177 studies, which, in total, included 34,808 people. Studies were typically about 7 weeks' long, but this ranged from 1 week to 52 weeks. Vitamin D products were found to work better than placebo (the base cream or ointment). Potent topical corticosteroids (strong, e.g. betamethasone dipropionate) and very potent (very strong, e.g. clobetasol propionate) topical corticosteroids were also effective. Some studies compared vitamin D products directly with potent or very potent corticosteroids. These products had similar effects when applied to the body, but corticosteroids worked better than vitamin D for scalp psoriasis. Treatment that combined vitamin D with a corticosteroid was more effective than vitamin D alone and more effective than the topical corticosteroid alone. Vitamin D products generally performed better than coal tar, but studies found conflicting results when comparing vitamin D with dithranol. Whether applied to the body or to the scalp, potent corticosteroids were less likely than vitamin D to cause 'local adverse events', such as skin irritation or burning, and people were therefore more likely to stop using vitamin D products. When studies examined whether topical treatments had effects within the body ('systemic adverse events'), we found no difference between placebo and any other treatment. However, this may be because many trials did not properly assess systemic adverse events, rather than because there really was no difference. More long-term studies would help doctors and people with psoriasis decide on the best way to treat this chronic condition.
+We included 183 studies with a total of 252,886 participants. Most studies were conducted in the hospital setting. Azithromycin and erythromycin were more commonly studied than clarithromycin and roxithromycin. Most studies (89%) reported some adverse events, or at least stated that no adverse events were observed. Drug companies supplied trial medications or funding, or both, in 91 studies. Funding sources were unclear in 59 studies. People treated with a macrolide antibiotic experienced gastrointestinal adverse events such as nausea, vomiting, abdominal pain, and diarrhoea more often than those treated with placebo. Taste disturbances were reported more often by people taking macrolides than those taking a placebo. However, as very few studies reported on these adverse events, these results should be interpreted with caution. Hearing loss was reported more often by people taking macrolide antibiotics, however only four studies reported this outcome. Macrolides caused less cough and fewer respiratory tract infections than placebo. We did not find any evidence that macrolides caused more cardiac disorders, liver disorders, blood infections, skin and soft tissue infections, changes in liver enzymes, appetite loss, dizziness, headache, respiratory symptoms, itching, or rashes than placebo. We did not find more deaths in people treated with macrolides than in those treated with placebo. Very limited information was available to assess if people treated with a macrolide antibiotic were at greater risk of developing resistant bacteria than those treated with placebo. However, bacteria that did not respond to macrolide antibiotics were more commonly identified immediately after treatment in people taking a macrolide than in those taking a placebo, but differences in resistance thereafter were inconsistent. The quality of the evidence ranged from very low (cardiac disorders, change in liver enzymes, liver disorders) to low (abdominal pain, death, diarrhoea, dizziness, hearing loss, skin and soft tissue infections, taste disturbance, wheeze) to moderate (appetite loss, blood infection, cough, fever, headache, itching, nausea, rash, respiratory symptoms, respiratory tract infections, vomiting).
+The review authors searched the medical literature up to August 2013 and identified four randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) containing 216 participants investigating different lens types. Lens materials studied were acrylic, silicone, heparin surface modified, and poly(methyl methacrylate). The trials included participants with different causes of uveitis, compared different lens types, and reported different outcomes. Due to these differences across trials, no meta-analysis (pooling of trial data) was performed. The largest trial (140 participants) was funded by a professional society. The other three trials did not report their funding sources. There is very limited evidence on which to determine the effects of different types of lens materials for people with uveitis. The results from the largest trial provide only preliminary evidence that acrylic lenses may perform better than silicone lenses in terms of improving vision and reducing the chances of post-surgical inflammation and complications. At this time, there is not enough data to conclude whether additional types of lenses are preferable to other types. Because the trials included small numbers of participants in each of the four lens-type groups, there is uncertainty in the results of the studies.
+The objective of this review was to evaluate the effectiveness of anti-histamines in children with prolonged cough that is not related to an underlying respiratory disease, that is, non-specific chronic cough. We included three therapeutic studies with 182 randomised participants. Two studies found that chronic cough significantly improved in both treatment and placebo groups with no difference between the two groups. One small study however described that children who had chronic cough associated with seasonal allergic rhinitis treated with cetirizine improved significantly more than children on placebo and this difference was evident by two weeks. Four studies that evaluated safety profiles included 3166 randomised participants and described a non significant increase in cough in participants who received the active medication. Despite the limitations of this review, our findings are similar to the review on anti-histamines for acute cough which showed no good evidence for or against the use of anti-histamines. In contrast to recommendations in adults with chronic cough, anti-histamines cannot be recommended as empirical therapy for children with chronic cough. Further research examining the effects of this treatment using child appropriate cough outcome measures is needed.
+The review included one study with 96 males with Hunter syndrome aged between 4.9 and 30.9 years of age. The trial compared idursulfase 0.5 mg/kg given either weekly or every-other week, or weekly infusions of placebo (a substance which contains no medication) and people were selected for one treatment or the other randomly. The study lasted 53 weeks. Current evidence is limited given there was only one randomised clinical trial found in the medical literature. As compared with placebo, enzyme replacement therapy with idursulfase in people with Hunter syndrome, led to some improvement in the individuals' ability to walk and a reduction in the excretion of abnormal mucopolysaccharides in the urine. To date there is no evidence available in the literature showing that treatment reduces complications of the disease related to quality of life and mortality. This trial was considered to be of overall good quality.
+We systematically searched for studies that examined the effect of task-oriented interventions for children with DCD. We found 15 appropriate studies involving 649 children from five to 12 years of age with a diagnosis of DCD. The participants were from Australia, Canada, China, Sweden, Taiwan, and the UK. Trials were conducted in hospital settings; at a university-based clinic, laboratory, or centre; in community centres; at home or school, or both at home and school. Most trials were small and of poor quality. The duration of the intervention was often short (i.e. less than six months). We were only able to combine the results from six studies in a meta-analysis, a statistical method to summarise the results from several independent studies. Together these studies suggest that task-oriented interventions have a moderately positive effect on movement problems. However, the finding from the two strongest studies alone indicated that task-oriented interventions do not improve movement problems. We were unable to use the remaining nine included studies in a meta-analysis because of insufficient data, or because the interventions used in the control groups (without a task-oriented intervention) were too different to combine. As a result, we were unable to perform any meta-analyses on many of our intended outcome measures or look at the effects of age, sex, severity of DCD, or how much intervention was received. Two studies reported no side effects. Through email correspondence, the authors of nine studies indicated that no injuries had occurred. The quality of the evidence was generally low, meaning we are very uncertain about the findings of this review. At the moment, task-oriented interventions may be useful for children with DCD in improving their performance on movement tests. We cannot be sure about benefits in other areas. Higher-quality research is needed to investigate and establish the effect of task-oriented intervention for children with DCD.
+The review authors searched the medical literature and identified 17 randomised controlled trials (9627 participants) investigating the different surgical interventions. Six of these trials suggested that PHACO gives a better outcome than ECCE. They suggest a better uncorrected visual acuity (UCVA) following PHACO than ECCE but the majority of the trials showed no difference in best corrected visual acuity (BCVA) between the two groups. The costs per procedure were not markedly different between the two techniques in a UK based study, however, a Malaysian study showed ECCE to be significantly cheaper. A study comparing MSICS and ECCE, advocated MSICS as the procedure of choice due to equal costs and better visual results. Two studies compared the results of PHACO and MSICS. Phacoemulsification having a significantly higher proportion of patients with UCVA > 6/18 (81.1% versus 71%) but there was no difference in BSCVA. Trials comparing costs of PHACO and MSICS are important for future research. Manual small incision surgery offers an alternative technique in developing countries as it provides acceptable visual outcomes when compared to PHACO yet is likely to be more economical as it avoids the initial outlay of costs of PHACO. It is important to remember that the studies in this review were based in a variety of countries and situations (hospital based or cataract camps); a knowledge of the setting is vital before drawing conclusions from the data.
+We found only one study of 22 participants to include in the review. The participants had been selected for the study because they had been diagnosed clinically with DLB or AD. This method of recruiting participants tends to exaggerate the accuracy of a test. The participants in the study had moderately severe dementia when they had the DAT imaging. Overall, the DAT imaging correctly classified 100% of the participants who had DLB and 92% of the participants who did not have DLB at postmortem. When we looked at only the 15 participants whom the doctors thought had DLB at the start of the study, then the DAT imaging correctly classified 100% of the participants who had DLB and 100% of the participants who did not have DLB at postmortem. The small size of the included study meant that we could not be very confident in these estimates of accuracy, and it is still possible that the test is considerably less accurate than this would suggest. We can conclude that DAT imaging is a promising test for diagnosing DLB, but it is important to note that we did not find any studies of participants in whom diagnosis may be more difficult, such as those with only mild dementia or those who have only one symptom to raise a suspicion of DLB.
+This review identified only three small randomized trials. The results showed that only aspects of work performance (for example, maximal test time, maximal distance at the end of the exercise test) were improved after aerobic exercise training programs. Further well-designed research on larger population samples is required to evaluate potential benefits for psychosocial aspects in adults with Down syndrome.
+We originally searched for clinical trials in 2002; and again in 2008 and 2014. We identified four studies that investigated the use of metoclopramide in placement of post-pyloric naso-enteral feeding tubes. The trials included a total of 204 adult participants; 108 participants were treated with metoclopramide, and 96 were given a placebo or no treatment. All four studies were done in hospitals in the USA. The number of participants included in the trials varied from 105 to 10. The trials were all performed before 1995. They were all small, and examined two different doses of metoclopramide (10 mg and 20 mg), delivered in two different ways (intravenously, and injected into muscle). The way in which they were conducted and reported was poor. Analysis of the four trials revealed that metoclopramide did not have a clear beneficial on the placement of post-pyloric naso-enteral feeding tubes. No harms (adverse reactions) were reported, though it was not clear how thoroughly the people running the trials recorded them. No costs of treatment were reported. The quality of the evidence is very low. The four trials were too small to identify any effect clearly; they also used different doses of metoclopramide, (tested against placebo or no treatment). It is unlikely that further studies will be performed to establish whether metoclopramide is helpful in placement of post-pyloric naso-enteral feeding tubes.
+The review identified only two randomised controlled trials, involving 262 patients with breast cancer. The data from these studies provide low-grade evidence for multidisciplinary rehabilitation in producing short-term gains at the levels of impairment (range of shoulder movement), psychosocial adjustment and quality of life after breast cancer treatment. None of the studies reported the longer-term functional outcomes of such care, the impact on caregivers or cost effectiveness of these programmes. Overall, the results of this review suggest that multidisciplinary rehabilitation is not harmful and may improve functional ability and quality of life in the short term. This review highlights the lack of robust trials in the field and the need for further high-quality trial-based research.
+We undertook this review because it was unclear which of the various salvage combinations, if any, was the most effect and the least toxic. We searched the literature up to November 2015 to find all relevant studies. Unfortunately, we were unable to find any good quality studies that compared the different types of salvage treatments. This is partly because the disease has a high cure rate with several combination chemotherapy options, but is also owing to the rarity of the disease that makes recruiting for large studies difficult. Hence we were unable to draw conclusions about how these drug combinations compare with regard to their effectiveness and side effects, and we urge researchers in this field to collaborate to provide this important evidence.
+Our review of fifty trials found that effective programmes to stop smoking are those that begin during a hospital stay and include counselling with follow-up support for at least one month after discharge. Such programmes are effective when administered to all hospitalised smokers, regardless of the reason why they were admitted to hospital, and in the subset of smokers who are admitted to hospital with cardiovascular disease. Adding nicotine replacement therapy to a counselling program increases the success rate of a program for hospitalised smokers.
+We included one small randomised trial (involving 98 women) that involved the drug rofecoxib, which is one type of COX inhibitor. The included study did not report any information about prevention of labour before full-term pregnancy. However, use of this COX inhibitor was associated with an increased risk of the baby being born before full term. We found insufficient data to make any recommendation about using COX inhibitors for preventing preterm labour. Future research should include the follow-up of babies to examine the short- and longer-term effects associated with using COX inhibitors during pregnancy.
+We searched for studies that evaluated the effectiveness of newborn resuscitation programmes in April 2014 and updated in March 2015 and found five community-based studies (187,080 deliveries) and nine mannequin-based studies (626 newborns). Moderate quality evidence from three studies suggested that training in newborn resuscitation probably decreases newborn deaths in the first seven days after birth. Low quality evidence from one study suggested that newborn resuscitation training may decrease newborn deaths in the first 28 days after birth. All three studies were performed in low-income settings and their findings may have limited applicability to high-income settings. We also found that teaching teamwork in addition to resuscitation training may improve team behaviour and decrease time for resuscitation (two studies, low quality evidence) but the effect on performance on resuscitation was uncertain. It is uncertain whether resuscitation programmes increase learners' knowledge and skills immediately and knowledge at six months because the quality of evidence was very low. Similarly, whether boosters to neonatal resuscitation help in retaining knowledge or performing resuscitation appropriately remain uncertain (the quality of evidence was very low). Also, whether visual or electronic aids for helping making decisions during resuscitation, improve resuscitation performance was uncertain (one study did not show effect but one electronic decision support tool with prompts improved resuscitation performance) (low quality evidence). We strongly encourage future studies to report outcomes related to long-term health, such as brain injury due to lack of oxygen, fits and long-term brain development. Effective methods to enhance teamwork behaviour, learning and retention of resuscitation knowledge and skills are needed.
+This review includes eight studies published from 1984 to 2014, in which 1746 participants were randomly assigned (1127 were included in the analyses) to receive dental sealant (or sealant together with fluoride varnish) or fluoride varnish applications, and the extent of tooth decay was compared. Participants were five to 10 years of age at the start of the trial and represented the general population. Some evidence suggests that applying resin-based sealants to the biting surfaces of permanent back teeth in children may reduce tooth decay in the permanent teeth of children by 3.7% over a two-year period, and by 29% over a nine-year period, when compared with fluoride varnish applications. Applying resin-based sealant together with fluoride varnish to the biting surfaces of the permanent back teeth may reduce tooth decay by 14.4% over a two-year period compared with fluoride varnish alone. Effects of applying glass ionomer sealants may be similar to those seen when fluoride varnish is applied, but evidence showing the similarity between interventions is of very low quality. Three studies reported that there were no associated adverse events from sealants or fluoride varnish applications; the other studies did not mention adverse events. Available evidence is of low to very low quality because of the small number of included studies, and because of problems with the way in which studies were conducted. Further, most studies reported a relatively short follow-up time.
+In November 2016, we searched for clinical trials where methadone was used to treat neuropathic pain in adults. We found three small studies, enrolling 105 participants, that met our requirements for the review. The studies were all quite different in their design: the methods of two studies reflected how frequently methadone is prescribed in practice, in that participants received it twice or three times daily. One trial had a more experimental design. All three trials had two phases. The lengths of the studies varied, from 20 days to around eight weeks for each phase. The studies were similar in that all administered low doses of methadone, which may or may not reflect the doses typically prescribed in clinical practice. Two studies looked at how many participants got at least 30% pain relief. Eleven of 29 participants receiving methadone achieved 30% pain relief versus seven of 29 receiving placebo. In one study, none of the 19 participants achieved a 50% reduction in pain intensity, either when receiving methadone or when receiving placebo (a sugar pill). These reductions in pain intensity have been shown to be important to patients. In addition, one study found improvements in average and maximum pain intensity and pain relief when comparing methadone with placebo. In the two studies that reported dropouts from the study, none of 29 participants dropped out because they thought methadone or the placebo was not helping their pain; whereas four of 29 dropped out because of side effects while taking methadone and three of 29 while taking placebo. One study reported how many participants had specific side effects, and found increased dizziness with methadone compared to placebo. There were no serious side effects or deaths reported. There was so little information from these studies that we concluded there was no convincing evidence to support or reject a meaningful benefit for methadone versus placebo or any other treatment. We rated the quality of the evidence as very low because there were only three small studies with different designs, and with few participants and events. In addition, the studies were probably not long enough to show how well methadone would work (or how safe it would be) over a longer time period. Very low quality evidence means that we are very uncertain about the results.
+This review found 20 studies that compared the effects of chronic disease management programmes in adults with asthma with the effects of usual care. The average age of the patients was 42.5 years, 60% were women, and they had moderate to severe asthma. Overall the evidence that was found was of moderate to low quality. Chronic disease management programmes for adults with asthma probably improve patients' quality of life, reduce the severity of the asthma, and improve breathing as demonstrated by improved performance in lung function tests after 12 months. It is unclear whether chronic disease management programmes improve the patients' abilities to manage their own asthma or decrease the number of hospitalisations or emergency visits.
+For this update, we conducted the search through to May 2018. We found 10 studies including 697 children and adolescents; four of these studies (326 participants) were new for this update. Four studies treated children with headache, one study treated children with juvenile idiopathic arthritis, one treated children with sickle cell disease, one included children with irritable bowel syndrome, and three studies included mixed samples of children, some who had headache and some with other chronic pain conditions. All studies delivered cognitive behavioural therapy. The average age of children receiving the interventions was 13 years. We looked at six outcomes: pain, physical functioning, depression, anxiety, side effects, and satisfaction with treatment. We split the painful conditions into two groups and looked at them separately. The first group included children with headache. The second group included children with other painful conditions (e.g. frequent stomach pain, musculoskeletal pain), known as 'mixed chronic pain'. Psychological therapies delivered remotely (primarily via the Internet) were helpful at reducing pain for children and adolescents with headache when assessed immediately following treatment. However, we did not find a beneficial effect for these children at follow-up. We found no beneficial effect of therapies for reducing pain intensity for children with other types of pain. Further, we did not find beneficial effects of remotely-delivered therapies on physical functioning, depression, or anxiety post-treatment for headache and mixed chronic pain conditions. However, there were limited data for mixed chronic pain conditions to draw conclusions from these outcomes, particularly at follow-up. Satisfaction with treatment was described in the trials and was generally positive. Six trials described side effects which were not linked to receiving psychological therapies. Currently, there are very few studies investigating this treatment. Caution should be taken when interpreting these results as they are based on a small number of studies with few children. Further studies in this area are likely to change our findings and may show this to be a useful treatment for reducing pain and improving functioning in children with long-term pain. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. We judged the quality of evidence as very low, downgraded due to differences between studies and assessments for the same outcomes, as well as differences identified in the statistical tests. However, this is a growing field and more trials with more participants using cognitive behavioural therapy and other psychological therapies are needed to determine if remotely-delivered therapies are helpful for young people with long-term pain.
+The authors of this review looked for evidence on the effectiveness of treatments which specifically focused on improving independence with daily activities (such as dressing, home chores, going shopping and interacting in the community) or had a focus on psychological and social issues in older people recovering from hip fracture. We were able to identify nine studies involving 1400 people who had sustained a hip fracture. Findings from three trials testing approaches taken while the patients were still in hospital using strategies such as reorientation, cognitive behavioural therapy and intensive occupational therapy did not show changed outcomes. Two trials tested specialist gerontological nurse-led care, which was delivered largely in the community. One of these, which included discharge planning, found some evidence of a reduction of poor outcome (defined as death, readmission or failure to return home) at three months from specialist-nurse led care, but the other trial found no differences in functional outcomes at 12 months compared with usual care. Trials testing other post-hospital interventions including group education programs after discharge and home rehabilitation (provided by a study physiotherapist and nursing staff) provided no evidence that these improved outcomes. This suggests that the transition between acute, rehabilitation and community care requires further attention. In all, the studies were too small and their quality too varied to recommend changes in practice.
+This review found four studies in which people who had undergone macular hole surgery with no ILM peeling were compared with those in whom the ILM was removed during the first surgery they had received. As well as reviewing published data from these four studies, we undertook an 'individual patient data (IPD) meta-analysis'. To undertake IPD meta-analysis one needs to collect all the raw data for each participant included in each of these RCTs before and after surgery and then combine all data together and analyse them. We were able to obtain data for each individual participant included in three of these four studies, which we then analysed and present in this review. Our results showed that at six and 12 months after the initial surgery to treat the macular hole the vision was no different between participants that received ILM peel and those who did not. At three months, however, the vision was better in those participants that received ILM peeling. More macular holes were closed and less re-operations had to be performed in participants who received ILM peeling with no differences in the number of complications between patients receiving ILM peeling or no peeling in the first surgery. There were no differences in the way participants perceived the benefits of the surgery. ILM peeling was found to be highly likely cost-effective, i.e. the cost of the treatment was justifiable by the benefits obtained from it. We conclude that ILM peeling compared with no peeling increases the chance for a macular hole to close with a single surgery and reduces the chances of people requiring additional surgery without unwanted side effects; as ILM peeling is very likely cost-effective, it may be considered the best available option for people with idiopathic FTMH.
+This review assessed overall and progression-free survival of optimal primary cytoreductive surgery for women with advanced epithelial ovarian cancer (stages III and IV). We found 11 retrospective studies that included more than 100 women and used a multivariate analysis (used statistical adjustment for important prognostic factors) and met our inclusion criteria. Analyses showed the prognostic importance of complete cytoreduction, where the residual disease is microscopic with no visible disease, as overall (OS) and progression-free survival (PFS) were significantly prolonged in these groups of women. PFS was not reported in all of the studies but was sufficiently documented to allow firm conclusions to be drawn. When we compared suboptimal (> 1 cm) versus optimal (< 1 cm) cytoreduction the survival estimates were attenuated but remained statistically significant in favour of the lower volume disease group, but there was no significant difference in OS and only a borderline difference in PFS when residual disease of > 2 cm and < 2 cm were compared. There was a high risk of bias due to the retrospective nature of these studies. Adverse events, quality of life (QoL) and cost-effectiveness were not reported by treatment arm or to a satisfactory level in any of the studies. During primary surgery for advanced stage epithelial ovarian cancer, all attempts should be made to achieve complete cytoreduction. When this is not achievable, the surgical goal should be optimal (< 1 cm) residual disease. Due to the high risk of bias in the current evidence, randomised controlled trials should be performed to determine whether it is the surgical intervention or patient-related and disease-related factors that are associated with the improved survival in these groups of women.
+Up to August 2016, this review found 67 trials, including data from over 110,000 participants. Smoking cessation data after six months or more were available for 35,969 participants. We examined a range of Internet interventions, from a low intensity intervention, for example providing participants with a list of websites for smoking cessation, to intensive interventions consisting of Internet-, email- and mobile phone-delivered components. We classed interventions as tailored or interactive, or both. Tailored Internet interventions differed in the amount of tailoring, from multimedia components to personalised message sources. Some interventions also included Internet-based counselling or support from nurses, peer coaches or tobacco treatment specialists. Recent trials incorporated online social networks, such as Facebook, Twitter, and other online forums. In combined results, Internet programmes that were interactive and tailored to individual responses led to higher quit rates than usual care or written self-help at six months or longer. There were not many trials conducted in younger people. More trials are needed to determine the effect on Internet-based methods to aid quitting in youth and young adults. Results should be interpreted with caution, as we rated some of the included studies at high risk of bias, and for most outcomes the quality of evidence was moderate or low.
+Several clinical trials reported effects of sulpiride augmentation for management of schizophrenia. We included four small trials which compared sulpiride plus clozapine with clozapine alone for very ill people. Evidence from the present review suggested that short-term sulpiride plus clozapine probably is more effective than clozapine alone in producing clinical improvement in some people. The evidence is, however, weak and prone to considerable bias. This is a good area for more research.
+We included 11 studies in the review, with a total of 745 participants. Five studies (334 patients) compared the efficacy of the Epley manoeuvre against a sham manoeuvre, three against other particle repositioning manoeuvres (Semont, Brandt-Daroff and Gans) and three with a control (no treatment, medication only, postural restriction). Patients were treated in hospital otolaryngology (ear, nose and throat) departments in eight studies and family practices in two studies. All patients were adults aged 18 to 90 years old, with a sex ratio of 1:1.5 male to female. For resolution of vertigo the Epley manoeuvre was significantly more effective than a sham manoeuvre or control. None of the trials that compared Epley versus other particle repositioning manoeuvres reported vertigo resolution as an outcome. When studies looked at the conversion from a positive to a negative Dix-Hallpike test (a test to diagnose BPPV) in the patients, the results significantly favoured the Epley treatment group when compared to a sham manoeuvre or control. There was no difference when Epley was compared with the Semont or Gans manoeuvre. In one study a single Epley treatment was more effective than a week of three times daily Brandt-Daroff exercises. Adverse effects were not often reported. There were no serious adverse effects of treatment. Rates of nausea during the repositioning manoeuvre varied from 16.7% to 32%. Some patients were unable to tolerate the manoeuvres because of cervical spine (neck) problems. The review of trials found that the Epley manoeuvre is safe and effective in the short term. Other specific sequences of physical movements, the Semont and Gans manoeuvres, have similar results. There was a low risk of overall bias in the studies included. All trials were randomised, with five studies applying sealed envelope or external allocation techniques. Seven of the trials blinded the assessors to the patients' treatment group and data on all outcomes for all participants were reported in most studies. This evidence is up to date to January 2014.
+In this review we sought, but could not find, any evidence from well-conducted randomised trials of the effects of non-medical day centres. Day centres are currently becoming prominent in service planning, but this is not based on good evidence as to their effectiveness for people suffering from severe mental illness. If a choice between facilities is available, people with serious mental illnesses and their carers are currently left to make their own judgements based on the evidence of experience and a few non-randomised studies.
+In this review, a total of 20 randomized controlled trials (RCTs) (representing 2674 participants) assessing the effects of SMT in patients with acute low-back pain were identified. Treatment was delivered by a variety of practitioners, including chiropractors, manual therapists, and osteopaths. Approximately one-third of the trials were considered to be of high methodological quality, meaning these studies provided a high level of confidence in the outcome of SMT. Overall, we found generally low to very low quality evidence suggesting that SMT is no more effective in the treatment of patients with acute low-back pain than inert interventions, sham (or fake) SMT, or when added to another treatment such as standard medical care. SMT also appears to be no more effective than other recommended therapies. SMT appears to be safe when compared to other treatment options but other considerations include costs of care.
+The review of trials found, when compared to conventional mechanical ventilation (CMV), high-frequency positive pressure ventilation (HFPPV) reduced the risk of air leak and triggered ventilation was associated with a shorter duration of ventilation. Compared to high-frequency oscillation, however, certain triggered modes of ventilation resulted in a greater risk of moderate to severe chronic lung disease and a longer duration of ventilation. Newer forms of triggered ventilation have only been evaluated in small randomised trials and have not been demonstrated to have advantages in important clinical outcomes.
+An update search for this review was carried out 28 January 2013; the review now includes 32 studies that assess the effects of pimozide for people with schizophrenia or similar mental health problems. Pimozide was compared with other antipsychotic drugs, placebo (‘dummy’ treatment) or no treatment. Results suggest that pimozide is probably just as effective as other commonly used ‘typical’ antipsychotic drugs (for outcomes such as treating mental state, relapse, leaving the study early). No studies included delusional disorders, so no information is available on this group of people. No evidence was found to support the concern that pimozide causes heart problems (although this may be result of the fact that the studies were small and short term and the participants did not receive doses above recommended limits of 20 mg/d). Pimozide may cause less sleepiness than other typical antipsychotic drugs, but it may cause more tremors and uncontrollable shaking. The claim that pimozide is useful for treating people with negative symptoms also is not supported and proven. However, the quality of evidence in the main was low or very low quality, studies were small and of short duration and were poorly reported. Large-scale, well-conducted and well-reported studies are required to assess the effectiveness of pimozide in the treatment of schizophrenia and other mental health problems such as delusional disorder. This plain language summary has been written by a consumer, Benjamin Gray (Service User and Service User Expert, Rethink Mental Illness).
+We searched for studies published in any language from January 1980 to July 2015. We found 98 unique studies, for a total of 116 test evaluations, involving 101,121 children. The number of participants ranged from 42 to 11,644 across test evaluations. The proportion of children with strep throat ranged from 9.5% to 66.6% across test evaluations. Important study design features were frequently not reported. The overall methodological quality of included studies was poor. For most studies, we had concerns about the ways in which participants were selected. On average, rapid tests for strep throat had a sensitivity (ability to correctly detect people with the disease) of 86% and a specificity (ability to correctly identify people who do not have the disease) of 95%. There was substantial variability in rapid test performance across studies, which was not explained by study characteristics, including methodological quality. The two types of rapid tests under evaluation seemed to have comparable sensitivity (85.4% versus 86.2% for enzyme immunoassays and optical immunoassays, respectively). Based on these results, we would expect that amongst 100 children with strep throat, 86 would be correctly detected with the rapid test while 14 would be missed and not receive antibiotic treatment. Of 100 children with non-streptococcal sore throat, 95 would be correctly classified as such with the rapid test while 5 would be misdiagnosed as having strep throat and receive unnecessary antibiotics.
+This review included eleven trials (2906 participants) and we were able to combine the data from nine trials with a total of 2637 participants (current to February 2016). Almost half of the participants were randomly assigned to wearing stockings for a flight lasting at least five hours while the other half did not wear stockings. None of the passengers developed a DVT with symptoms (slowly developing leg pain, swelling and increased temperature) and no serious events (a blood clot in their lungs (pulmonary embolism) or dying) were reported. Passengers were carefully assessed after the flight to detect any problems with the circulation of blood in their legs, even if they had not noticed any problems themselves. Wearing compression stockings resulted in a large reduction in symptomless DVT among airline passengers who were allocated to wear compression stockings compared to those allocated not to wear compression stockings. This difference in symptomless DVT between the two groups is equivalent to a reduction in the risk from a few tens per thousand passengers to two or three per thousand. People who wore stockings had less swelling in their legs (oedema) than those who did not wear them. Fewer passengers developed superficial vein thrombosis when wearing compression stockings than those not wearing stockings. Not all the trials reported on possible problems with wearing stockings but in those that did, the researchers said that the stockings were well-tolerated, without any problems. High-quality evidence shows that airline passengers wearing compression stockings develop less symptomless DVT and low-quality evidence shows that leg swelling is reduced when compared to not wearing compression stockings. Quality of the evidence was limited by the way that swelling was measured. There is moderate-quality evidence that superficial vein thrombosis may be reduced in passengers who wear compression stockings. We cannot assess the effect of wearing stockings on death, pulmonary embolism or symptomatic DVT because no such events occurred in these trials. Randomised trials to assess these outcomes would need to include a very large number of people.
+Seven randomised controlled trials involving a total of 1919 participants were included. All trials involved people, predominantly young adults, participating in regular sporting activities. Some trials were compromised by poor methodology, including lack of blinding and incomplete outcome data. Four trials, including 287 participants, examined interventions directly targeted at preventing hamstring injuries. Three of these trials, which tested hamstring strengthening protocols, had contradictory findings and we could not conclude whether strengthening exercises of the hamstrings was beneficial or not. One small trial found that manual therapy (involving manipulation, massage and specific stretches to joints and muscles of the spine and leg) may prevent injuries of leg muscles, including the hamstrings. Three inconclusive trials tested interventions for preventing all leg injuries for which data for hamstring injury were available. Two trials found no evidence for an effect for balance training on a wobble board (proprioceptive protocol). One trial found no evidence for a warm up/cool down and stretching protocol for distance runners. Based on currently available research findings, no specific intervention can be recommended for decreasing the risk of incurring hamstring injuries.
+We included four randomised controlled trials involving a total of 422 women in this review. The trials did not demonstrate any differences between magnesium maintenance therapy and placebo or other treatments (ritodrine or terbutaline) in the prevention of preterm birth or perinatal deaths. The trials were too small to exclude either important benefits or harms from magnesium maintenance therapy. Magnesium was less likely than the alternative tocolytics (betamimetics) to result in side effects, particularly palpitations or tachycardia, although diarrhoea was more likely. This finding is based on very few studies of low quality, and none of them looked at the infants' later development.
+This review of clinical trials concluded that there is some evidence to show that flavonoids can help heal venous leg ulcers, however, many trials were not reported well, and we could not know for certain whether the apparently beneficial effects were real or not. This meant that we could not draw firm conclusions, or recommend routine use of flavonoids for people with leg ulcers. Larger and better conducted trials are needed to assess the true clinical effect of flavonoids.
+The review of trials found that this is an effective surgical technique for stress and mixed urinary incontinence in women, resulting in long-term cure for most women. It provides better cure rates compared to anterior colporrhaphy a (suturing of the top wall of the vagina) and needle suspension surgery (passing a needle with sutures at the sides of the urethra to lift up the tissues beside it).New techniques, particularly sling operations (including the use of tapes to lift up the urethra)and keyhole (laparoscopic) colposuspension, look promising but need further research particularly on long-term performance. Procedures involving surgery to insert a tape under the urethra showed better cure rates in the medium and long term, compared to open colposuspension. In terms of costs, a non-systematic review of economic studies suggested that open retropubic colposuspension would be cheaper than laparoscopic colposuspension, but more expensive than tension-free vaginal tape (TVT). Laparoscopic colposuspension allows for faster recovery compared to open colposuspension. Studies did not reveal a higher complication rate with open colposuspension compared with the other surgical techniques, although pelvic organ prolapse was found to be more common. Abnormal voiding was less common after open colposuspension compared to sling surgery. Limited information was available on the long term adverse events of open colposuspension and its effect on the quality of life.
+The data for nine clinical trials containing a total of 3622 patients were analysed. In the trials of less than 12 weeks that reported improvement of general well-being and mental state, there was no statistically significant difference between typical antipsychotics and aripiprazole. However, when looking at adverse effects, people on aripiprazole were less likely to suffer from movement side effects, blurred vision, high levels of the hormone prolactin or increased heart rate. These people were also less likely to withdraw their consent to being in the study in short (less than 12 weeks) and longer (more than 12 weeks) trials. Conversely, people on typical antipsychotics were significantly less likely to feel dizzy or nauseous. These trials were all quite different from each other - they had varying settings, enrolled different groups of people, were for varying lengths of times (from 24 hours to 52 weeks) and compared aripiprazole to different first generation antipsychotics. This made it difficult to compare outcomes from trial to trial. In addition, a lot of the data were not able to be used because measurements were not given in full. This medication looks promising but there needs to be more trials, particularly longer-term well-planned trials. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).
+A form of treatment called Tinnitus Retraining Therapy (TRT) is used in many countries to treat this symptom. This treatment comprises a form of educational counselling and sound therapy given according to a specific protocol. Only one study, involving 123 participants, matched the inclusion criteria for this review. Although this study suggested considerable benefit for TRT in the treatment of tinnitus the study quality was not good enough to draw firm conclusions. No side effects of treatment were described. Further research is required.
+This summary of an update of a Cochrane review presents what we know from research about the effects of exercise for people with OA of the knee. After searching for all relevant studies up to May 2013, we added 23 new studies since the last version of the review, now including 54 studies (3913 participants), most on mild to moderate symptomatic knee OA. Except for five studies in which participants enrolled in a Tai Chi-based programme, most participants underwent land-based exercise programmes consisting of traditional muscle strengthening, functional training and aerobic fitness programmes, which were individually supervised or were provided during a class; these individuals were compared with people who did not exercise. Evidence from 44 studies (3537 participants) shows the effects of exercise immediately after treatment; 12 studies provided data on two to six-month post-treatment sustainability. Here we report only results for the immediate treatment period. Pain on a scale of 0 to 100 points (lower scores mean reduced pain). • People who completed an exercise programme rated their pain at 12 (10 to 15) points lower at end of treatment (12% absolute improvement) compared with people who did not exercise. • People who completed an exercise programme rated their pain at 32 points. • People who did not exercise rated their pain at 44 points. Physical function on a scale of 0 to 100 points (lower score means better physical function). • People who completed an exercise programme rated their physical function at 10 points (8 to 13 points) lower at end of treatment (10% absolute improvement) compared with people who did not exercise. • People who completed an exercise programme rated their physical function at 28 points. • People who did not exercise rated their physical function at 38 points. Quality of life on a scale of 0 to 100 points (higher score means better quality of life). • Overall, people who completed an exercise programme rated their quality of life at 4 points (2 to 5 points) higher at the end of treatment (4% absolute improvement). • People who completed an exercise programme rated their quality of life at 47 points. • People who did not exercise rated their quality of life at 43 points. Withdrawals. • One fewer persons out of 100 dropped out of the exercise programme (1% absolute decrease). • Out of 100 people in exercise programmes, 14 dropped out. • Out of 100 people who did not exercise, 15 dropped out. High-quality evidence shows that among people with knee OA, exercise moderately reduced pain immediately after cessation of treatment and improved quality of life only slightly, without an increase in dropouts. Further research is unlikely to change the estimate of these results. Moderate-quality evidence indicates that exercise moderately improved physical function immediately after cessation of treatment. Further research may change the estimate of these results. Most clinical studies have provided no precise information on side effects such as injuries or falls sustained during exercise, but we would expect these to be rare. Eight studies reported increased knee or low back pain attributed to the exercise programme, and all identified studies reported no injuries.
+The evidence is current to January 2018. We included nine randomized controlled trials (517 participants). The trials included between 40 and 73 participants. Although use of the LMA procedure may shorten the period during which the airway is insecure, the procedure is more likely to have to be changed. Only one small study of 40 participants reported the number of people who died from any cause during their stay in hospital, without any difference between treatment groups. No deaths were caused by the procedure itself in the five studies (281 participants) that reported this outcome. Eight studies reported the number of participants with one or more serious adverse events, showing no clear evidence of a benefit for a laryngeal mask airway or endotracheal tube (467 participants). Serious adverse events that occurred were irregular rhythm of the heart beat, low blood oxygen concentrations, accidental displacement of the ETT or LMA, damage of parts of the ETT, minor bleeding and reflux of swallowed food into the airways. Neither method was superior in terms of preventing any adverse event. The duration of the procedure was clearly shorter in the laryngeal mask group, by well over a minute (6 studies, 324 participants). This benefit was associated with a higher risk of needing to change over to a different procedure (8 studies, 434 participants). Longer-term complications were not sufficiently investigated. We judged the quality of evidence to be very low or low because we could not obtain important information on the methods used to conduct these studies. We had serious concerns about study limitations, the small number of participants in the studies and the variation in findings within and between studies (imprecision). Most studies were limited in reporting on patient relevant outcomes. The first study was published in 2002 and techniques have improved over time since then.
+We conducted a search up to 6 January 2014 and included eight studies which enrolled 948 participants in total. Four studies of corticosteroids in the treatment of dengue-related shock assessed if corticosteroids could improve survival, but these studies were small and older than 20 years. The evidence we found is of very low quality and do not provide any reliable evidence for corticosteroids for treating dengue-related shock. Four trials evaluated whether corticosteroids provided at an early stage of dengue could prevent development of complications of severe dengue. These trials were more recent, but data were insufficient to be sure whether corticosteroids have an effect on the course of the disease.
+In this review we found 79 randomised controlled trials (RCTs) (90 comparisons) including 24,308 patients worldwide, comparing collaborative care with routine care or alternative treatments (such as consultation-liaison) for depression and anxiety. There were problems with the methods in some of the studies. For example, the methods used to allocate patients to collaborative care or routine care were not always free from bias, and many patients did not complete follow-up or provide information about their outcomes. Most of the studies focused on depression and the evidence suggests that collaborative care is better than routine care in improving depression for up to two years. A smaller number of studies examined the effect of collaborative care on anxiety and the evidence suggests that collaborative care is also better than usual care in improving anxiety for up to two years. Collaborative care increases the number of patients using medication in line with current guidance, and can improve mental health related quality of life. Patients with depression and anxiety treated with collaborative care are also more satisfied with their treatment.
+This systematic review investigated the efficacy of lithium compared to that of placebo in the maintenance treament of mood disorders (unipolar and bipolar disorder). Nine randomised studies (reporting on 825 participants) were included in the review. Lithium was more effective than placebo in preventing relapse in mood disorder overall. Lithium was more effective than placebo in bipolar disorder, though estimates of the size of the effect varied between studies. In unipolar disorder, lithium appeared to be more effective than placebo but the evidence for this was less clear cut.  Lithium should be considered for maintenance treatment in bipolar disorder and, although the evidence is less reliable, it may be considered as one of a range of treatments with possible benefit in preventing relapse in unipolar disorder. When considering lithium maintenance therapy, patients and clinicians should take into account the evidence of efficacy, side effects and the individual's likely adherence to the recommended treatment regimen. Caution should be exercised in abruptly stopping lithium therapy in patients who have been taking it successfully for some time, due to the high risk of relapse.
+Endometriosis is a disease characterised by the presence of endometrial tissue (the lining of the womb) outside the cavity of the womb. Many women with the disease suffer from menstrual pain and some suffer from infertility. Infertile women with endometriosis are often treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) but have a lower chance of becoming pregnant compared to women who are infertile with blocked tubes. It has been suggested that giving GnRH agonists before IVF or ICSI could increase the chances of pregnancy. We have reviewed the literature and found that treating women for three to six months with GnRH agonists before IVF or ICSI increases the odds of clinical pregnancy four-fold. However, at present there is no information on the effect of this treatment on the incidence of ectopic pregnancy, multiple pregnancies or complications arising for the women or their offspring.
+We found 62 relevant studies, of which 57 randomly allocated participants to receive either MT or a control therapy (randomised controlled trials) and five provided both therapies to all participants, but in random order (cross-over trials). The studies involved a total of 1982 participants with a mean age of 59 years (30 to 73 years) after stroke. Mirror therapy was provided three to seven times a week, between 15 and 60 minutes for each session for two to eight weeks (on average five times a week, 30 minutes a session for four weeks). At the end of treatment, mirror therapy moderately improved movement of the affected upper and lower limb and the ability to carry out daily activities for people within and also beyond six months after the stroke. Mirror therapy reduced pain after stroke, but mainly in people with a complex regional pain syndrome. We found no clear effect for visuospatial neglect. The beneficial effects on movement were maintained for six months, but not in all study groups. No adverse effects were reported. The studies provide moderately-reliable evidence that MT improves movement (motor function, motor impairment) and the performance of daily activities. However, there was only low reliability that MT decreases pain and visuospatial neglect. This may be due to the small number of studies. Further research is needed, with larger methodologically-sound studies.
+Ten different herbal medicines were tested in ten randomised trials in patients with chronic hepatitis C. The present systematic review found no significant antiviral effect of the herbal medicines when compared with placebo, but the data suggest that some herbal medicines in combination with interferon may have effects on the clearance of HCV RNA and on normalisation of liver enzymes. However, there is no strong evidence for any efficacy of these medicinal herbs for chronic hepatitis C due to the fact that most positive effects came from clinical trials with low methodological quality. Medicinal herbs for hepatitis C virus infection should not be used outside well-designed, randomised clinical trials.
+We searched for clinical trials comparing slow versus faster rates of increase in the amount of milk fed to newborn infants who were very low birth weight. When performing searches updated in June 2017, we found 10 trials involving 3753 infants in total. Combined analysis of these trials did not show an effect of slow feeding on the risk of necrotising enterocolitis or death (moderate-quality evidence) but did suggest that infants fed more slowly might have higher risk of acquiring a severe infection than infants fed more quickly (low-quality evidence). Slow feeding does not appear to provide benefits and may cause some harms.
+No trials were found examining the efficacy of electroconvulsive therapy or behavioural therapy. We identified three trials which examined antidepressant drugs. The review found that there is not enough evidence from the trials about the effects of antidepressant drugs for the treatment of depression in people with Parkinson's disease. Adverse effects in trials so far have not been severe, and included visual hallucinations and confusion.
+We included five trials, which involved a total of 1577 women, comparing cerclage with no cerclage in women with either singleton and multiple gestations. After excluding singletons, our final analysis included 128 women, of which 122 were pregnant with twins, and six were pregnant with triplets. Cerclage was indicated by obstetric history in two trials (n = 73 women) and transvaginal ultrasound in three trials (n = 55 women). When cerclage was compared with no cerclage in women with multiple gestations, there was no difference in perinatal deaths or neonatal ill health, or preterm birth rates. However, the number of women included in the five studies was insufficient to provide meaningful conclusions. The long-term effect of cerclage on neurodevelopmental outcomes in the surviving infants and maternal infection and side- effects could not be estimated. It was therefore unclear if cerclage for women with multiple pregnancies puts the health of either the mothers or the infants at risk in any way. The five included studies were generally considered to be of average to above average quality, but three of the studies were difficult to assess fully because of missing methodological information. We did not find any studies comparing different indications for cerclage (obstetric history-indicated versus ultrasound-indicated cerclage) or comparing cerclage to another intervention (such as progesterone).
+We included three studies enrolling 271 infants in this review. These studies showed that infants who's tubes contained an antibiotic solution were less likely to develop an infection. One side effect of this treatment could be the development of 'super' bugs. Super bugs cause a type of infection that some antibiotics may not be able to fight. Our included studies did not show any evidence that antibiotic lock was more or less likely to produce super bugs compared with no antibiotic lock, but to show this convincingly the studies would need to be much larger. The rates of death from an infection caused by the tubes were not reduced by the antibiotic lock. Relatively few infants were enrolled in the three included studies. Two of the three included studies had overall low risk of bias, and the remaining study had high risk of bias from two sources: i). Selection bias, namely, the manner in which group allocation took place (based on the room infants were nursed in) posed a major concern as to whether the allocation was truly random, and ii). Performance bias, namely, non-blinding of the people who were involved in the care of the infants might have contributed to differential care and/or expectations which might have affected the results. Based on a small number of trials and infants, antibiotic lock solution appears to be effective in preventing catheter-related blood infections in infants. However, as each included study used a different antibiotic and antibiotic resistance could not be reliably assessed, the evidence to-date is insufficient to determine the effects of antibiotic lock on infections in infants.
+We conducted a wide search of medical and dental literature up to 10 February 2016. We identified 20 studies that randomised participants to groups receiving different forms of retreatment of periapical lesions. These studies evaluated nine different comparisons: surgical versus non-surgical treatment (two studies, one monitoring participants for up to 10 years); two diagnostic radiographic techniques (one study); the occurrence of postoperative infection with or without antibiotics (one study); use of different devices for enhancing the surgeon's view during the most critical steps of the surgical procedure (one study); the aesthetic appearance of the gum next to the treated tooth and pain after operation when two different types of gingival incision were used (two studies); use of minimally invasive ultrasonic devices or traditional rotating burs to manage the tip of the root (one study); use of different materials for filling the root-end (seven studies); filling of the periapical lesion with a grafting material (four studies); and exposure of the surgical site to a low energy level laser to reduce pain (one study). There is no evidence that a surgical approach leads to better results compared with non-surgical retreatment at one year (or at four or 10 years) after intervention. However, people treated surgically reported more pain and swelling during the first week after treatment. Different surgical techniques were evaluated. Healing at one-year follow-up seemed to be improved by use of ultrasonic devices, instead of the traditional bur, for root-end preparation. There was some evidence of better healing at one-year follow-up when root-ends were filled with mineral trioxide aggregate compared with their being treated by smoothing of orthograde gutta percha root filling. Use of a graft composed of a gel enriched with the patient's own platelets applied to the defect during the surgical procedure significantly reduced postoperative pain. Exposure to a low energy level laser did not apparently reduce pain at the surgical site. A small gingival incision may preserve the gum between two adjacent teeth, improving the aesthetic appearance and causing less pain after surgery. There was no evidence that use of antibiotics reduces the occurrence of postoperative infection (although when the procedure is done well, infection is an extremely rare event). Different ways of enhancing the surgeon's view did not lead to different results at least one year after operation, and results of retreatment were independent of the radiographic technique used to make the diagnosis. We judged the quality of the evidence to be poor; therefore we cannot rely on the findings. Only one study was at low risk of bias;we judged the majority to be at high risk of bias. It is difficult to draw conclusions, as the evidence currently available is of low to very low quality. More randomised controlled trials conducted to high standards are needed to find out the effects of the surgical versus non-surgical approach and, when surgery is used, which materials, devices or operative protocols are best for improving lesion healing and reducing patient discomfort.
+The review found that few trials have been performed to investigate its effectiveness. There is currently not enough evidence that adding chemotherapy to other treatments helps to treat the recurring cancer or to improve survival. However, chemotherapy may be an option, and further trials are underway.
+Overweight and obesity are common health problems and increase the risk of developing several serious health conditions. The standard treatment for overweight and obesity is to help patients change their diet and exercise habits. Treatment programs in which patients interact with a computer may help people make these changes, and improve their ability to lose weight and keep it off. We looked for randomized or quasi-randomized trials in which an interactive computer intervention was compared with no treatment, a limited treatment such as usual care or paper materials, or an in-person treatment to help people lose weight or keep it off. We included 14 weight loss studies with a total of 2537 participants, and four weight maintenance studies with a total of 1603 participants. The length of treatment ranged from four weeks to 30 months. At six months, computer-based interventions led to greater weight loss than minimal interventions (mean difference -1.5 kg; 95% confidence interval (CI) -2.1 to -0.9; two trials) but less than in-person treatment (mean difference 2.1 kg; 95% CI 0.8 to 3.4; one trial). At six months, computer-based interventions were superior to a minimal control intervention in limiting weight regain (mean difference -0.7 kg; 95% CI -1.2 to -0.2; two trials), but not superior to infrequent in-person treatment (mean difference 0.5 kg; 95% -0.5 to 1.6; two trials). Three weight loss studies estimated the costs of computer-based interventions compared to usual care, however two of the studies were 11 and 28 years old, and these estimates are probably not relevant to interventions using current technology, while the third study was carried out in active duty military personnel, and it is unclear whether costs would be similar in other settings. One weight loss study reported the cost-effectiveness ratio for a weekly in-person weight loss intervention relative to a computer-based intervention as USD 7177 (EUR 5678) per life year gained (80% CI USD 3055 to USD 60,291 (EUR 2417 to EUR 47,702)). It is unclear whether this is relevant to other studies. No studies had information on health-related quality of life, morbidity, complications or adverse effects. Compared to no intervention or minimal interventions (pamphlets, usual care), interactive computer-based interventions are an effective intervention for weight loss and weight maintenance. Compared to in-person interventions, interactive computer-based interventions result in smaller weight losses and lower levels of weight maintenance. The amount of additional weight loss, however, is relatively small and of brief duration, making the clinical significance of these differences unclear.
+Their effectiveness for treatment or prevention of women’s anxiety during pregnancy needs to be confirmed in clinical trials, as anxiety during the different stages of pregnancy can affect women’s health and have consequences for the child. This review identified few studies that examined this. We included eight randomized controlled studies with 556 women in this review. Based on these studies, there is some not strong evidence for the effectiveness of mind-body interventions in the management of anxiety during pregnancy, labor, or in the first four weeks after giving birth. Compared with usual care, imagery may have a positive effect on anxiety during labor. Another study showed that imagery had a positive effect on anxiety and depression in the immediate postpartum period. Autogenic training might be effective for decreasing women's anxiety before delivering. No harmful effects were reported for any mind-body interventions in the studies included in the review. The studies used different mind-body interventions, sometimes as part of a complex intervention, that they compared with usual care or other potentially active interventions using diverse outcome measures. Several studies were at high risk of bias, had small sample sizes and high dropout rates.
+The optimum treatment for infantile spasms has yet to be proven with confidence, in part because of the different aims of existing studies. However, some useful conclusions can be drawn from current evidence. Infantile spasms is a rare seizure disorder commonly associated with severe learning difficulties. Many different treatments are currently used worldwide in the treatment of this disorder, and many more have been tried in the past, often with little success. Not all treatments are licensed for use in all countries. Most treatments are associated with significant adverse effects. Additional research is needed to explore the long-term benefits of different therapies for seizure control and for neurodevelopment. Two studies have shown that a placebo is not as good as an active treatment in resolving the spasms. The strongest evidence suggests that hormonal treatment (prednisolone or tetracosactide depot) leads to resolution of spasms faster and in more infants than does vigabatrin. Responses without subsequent relapse may be no different, but one study suggested that hormonal treatment (prednisolone or tetracosactide) might improve long-term neurodevelopmental outcomes in infants and young children for whom no underlying cause for their infantile spasms has been identified. This makes hormonal treatment more attractive, at least for this group of infants. More information and further research are needed to compare currently available therapies.
+We identified six clinical studies (2275 participants) addressing this question, half of which were randomised controlled trials, where patients were randomly selected to get or not to get the vaccine. Two other studies showed that adults with cancer who were vaccinated were found to have lower rates of death, but these studies were not randomised. One small randomised study showed a similar mortality rate in vaccinated and non-vaccinated patients. Pooling (combining) results from the different studies was not possible because of different methods or different ways the results were reported. There was a lower rate of influenza-like illness (any febrile respiratory illness), pneumonia, confirmed influenza and hospitalisation for any reason, among vaccinated people in at least one study. No side effects to the vaccine were reported in these studies. The review also included a trial comparing the regular vaccine to a vaccine containing an adjuvant that is supposed to increase the immune response. This randomised trial was small and did not find differences in all clinical outcomes examined. The strength of evidence is limited by the low number of studies and by their low methodological quality (high risk of bias). It is unlikely that there will be any future large-scale controlled trials to investigate this issue. The current evidence, although weak, suggests a benefit for influenza vaccination amongst adults with cancer and the vaccine was not found to be harmful. Influenza vaccines given to adults with cancer contain an inactivated virus that cannot cause influenza or other viral infection.
+Three randomized controlled trials were included involving 339 women of reproductive age who required IVF treatment due to tubal factor infertility, anovulation, male factor infertility, endometriosis or fertility of unknown cause. These studies compared the outcome of IVF cycles in women whose cyst was drained versus the outcomes when the cyst was not drained. The evidence was current to April 2014. None of the included studies reported live birth rates or adverse event rates. There was insufficient evidence to determine whether there was any difference in the pregnancy rate, the number of follicles recruited, or the number of eggs retrieved, between women who had their cyst drained and women who did not. The quality of the evidence was low or very low for all comparisons, the main reasons for this being small study numbers, low numbers of events and poor reporting of study methods. There was inconsistent reporting of study findings in one RCT, which meant that some of the data could not be used
+We identified 42 studies (3262 participants) examining the effects of these solutions on patient outcomes. When compared to conventional peritoneal dialysis solutions, we found that neutral pH, low glucose breakdown product peritoneal dialysis solutions resulted in better preservation of a patient's own kidney function including urine output. Patients who received non-glucose based (icodextrin) peritoneal dialysis solutions achieved greater fluid removal with their dialysis and were 70% less likely to experience uncontrolled episodes of fluid overload. No significant harms were identified with any of the biocompatible peritoneal dialysis solutions. Many of the studies were limited by small size, short follow-up duration, suboptimal methodological quality, and inconsistent reporting of outcomes. Consequently, the effects of biocompatible peritoneal dialysis solutions on the length of time that a patient is able to either remain on peritoneal dialysis or stay alive are uncertain. Compared with peritoneal dialysis patients treated with conventional peritoneal dialysis solutions, those treated with biocompatible solutions experience important benefits including better preservation of their own kidney function and urine volume with neutral pH, low glucose breakdown product peritoneal dialysis solutions and more effective prevention of fluid overload due to increased dialysis-related fluid removal with icodextrin. Whether these benefits help patients to stay on peritoneal dialysis longer or live longer are uncertain and require further study.
+The data reviewed also lead to the conclusion that a diluted proprietary quinine solution (made less acidic by adjustment to a pH of 4.5) given intrarectally using a syringe for two to three days has less harmful effects compared with intramuscular quinine given for the same time period. Administration of intrarectal quinine (made less acidic by adjustment to a pH of 4.5) is significantly less painful than intramuscular injection of quinine. More trials are needed for patients with severe malaria and in adults.
+The doses of eplerenone used in these studies ranged from 25 mg to 400 mg daily. These studies followed patients for 8 to 16 weeks while on therapy. None of the studies reported on the clinically meaningful outcomes of eplerenone, such as whether eplerenone can reduce heart attacks, stroke, or death compared to placebo. Only three of the five studies reported on side effects. There is currently no evidence that eplerenone has a beneficial effect on life expectancy or complications rleated to hypertension (e.g. heart attack, stroke). Evidence for risk of side effects with eplerenone is limited and of poor quality; it is difficult to tell the extent of possible harm with eplerenone versus placebo. This meta-analysis shows that eplerenone 50 to 200 mg/day reduces systolic blood pressure by approximately 9 mmHg and diastolic blood pressure by 4 mmHg compared to taking no medication. We judged the five included trials to be of moderate quality, as authors did not extensively describe portions of their methodology.
+In January 2017, we searched for clinical trials in which tramadol was used to treat neuropathic pain in adults. Six studies met the inclusion criteria, randomising 438 participants to treatment with tramadol or placebo. Study duration was between four and six weeks. Not all reported the outcomes of interest. Our definition of a good result was someone who had a high level of pain relief and was able to keep taking the medicine without side effects that made them stop treatment. Three small studies reported that pain was reduced by half or better in some people. Pain reduction by half or better was experienced by 5 in 10 with tramadol and 3 in 10 with placebo. Side effects were experienced by 6 in 10 with tramadol and 3 in 10 with placebo, and 2 in 10 with tramadol and almost no-one with placebo stopped taking the medicine because of side effects. The evidence was mostly of low or very low quality. This means that the research does not provide a reliable indication of the likely effect and that the likelihood is very high that the effect will be different from what is shown in the analysis of these trials. Small studies like those in this review tend to overestimate results of treatment compared to the effects found in larger, better studies. There were also other problems that might lead to over-optimistic results. The low-quality evidence and the lack of any important benefit mean that we need new, large trials before we will know if tramadol is useful for the management of neuropathic pain.
+The review analysed the effects of diuretics working on the deep part of the small kidney tubes (loop diuretics). The review of trials found that diuretics, given from a single dose to one week's treatment, inconsistently improved lung function and oxygen levels in the blood. There was not enough evidence to show any improvement in long-term outcome.
+We included 14 studies with a total of 978 randomised children with stones in either the kidney or ureter, which connects the kidney to the bladder. The number of children in the studies varied from 22 to 221 children. There were seven trials of different types of surgery, four trials of medications and one study that compared medication with surgery. The amount of time the trials followed participants for ranged from one week to one year. Shock waves versus medication to dissolve stones: we are uncertain about the effect on successful removal of stones, serious complications and the need for a second procedure to treat the stones. Shock waves given slowly versus shock waves given fast: we are uncertain about the effect of slow shock waves on successful removal of stones. We are also uncertain about the effect on serious complications and the need for other procedures. Shock waves versus treatment using a scope through the bladder to break up the stone: we are uncertain about the effect of shock waves on successful removal of stones compared to using a scope. We are also uncertain about the effect on serious complications and the need for other procedures. Shock waves versus treatment using a scope through the skin into the kidney: shock waves are likely less successful in the removal of stones. Shock waves appears to reduce severe adverse events but more often secondary procedures are needed to remove all the stones. Use of a scope through the kidney with a drainage tube afterwards versus without a drainage tube: we are uncertain about the effect on successful removal of stones, serious complications or the need for more procedures. Use of a scope through the kidney with a regular versus very small ("mini") tube through the skin: successful removal of stones are likely similar in both procedures. We did not find any data relating to serious adverse events. We are uncertain about the effect on the need for another procedure. Alpha-blockers versus placebo with or without ibuprofen: alpha-blockers may increase successful removal of stones. We are uncertain about serious complications and the need for more procedures. The quality of evidence for most outcomes was very low. This means that we are very uncertain about most of the review findings.
+Evidence is current to 25th May 2017. We included 11 trials with a total of 3555 participants evaluating prescribing strategies for people with respiratory tract infections. Ten of these studies compared strategies of delaying antibiotics with immediate antibiotics. Four studies compared delayed antibiotics with no antibiotics. Of the 11 studies, five included only children (1173 participants), two included only adults (594 participants), and four included children and adults (1761 participants). The studies investigated a variety of respiratory tract infections. One study involving 405 participants was new for this update. There were no differences between immediate, delayed, and no antibiotics for many symptoms including fever, pain, feeling unwell, cough, and runny nose. The only differences were small and favoured immediate antibiotics for relieving pain, fever, and runny nose for sore throat; and pain and feeling unwell for middle ear infections. Compared to no antibiotics, delayed antibiotics led to a small reduction in how long pain, fever, and cough persisted in people with colds. There was little difference in antibiotic adverse effects, and no significant difference in complications. Patient satisfaction was similar for people who trialled delayed antibiotics (86% satisfied) compared to immediate antibiotics (91% satisfied), but was greater than no antibiotics (87% versus 82% satisfied). Antibiotic use was greatest in the immediate antibiotic group (93%), followed by delayed antibiotics (31%), and no antibiotics (14%). In the first month after the initial consultation, two studies indicated that participants were no more likely to come back and see the doctor for delayed or immediate prescribing groups. Excluding the first month, one study found that participants were no more likely to return to see the doctor in the 12 months after the delayed or immediate prescription for another respiratory infection, and another study found that participants were more likely to come back and see the doctor in the next 12 months if they had had an immediate prescription compared to a delayed prescription. Two studies including children with acute otitis media reported on the use of other medicines in delayed and immediate antibiotic groups. There was no difference in the use of ibuprofen, paracetamol, and otic drops in one study. In the other study, fewer spoons of paracetamol were used in the immediate antibiotic group compared with the delayed antibiotic group on the second and third day after the child's initial presentation. No included studies evaluated herbal or other forms of complementary medicine. No included studies evaluated antibiotic resistance. Overall, the quality of the evidence was moderate according to GRADE assessment. When doctors feel it is safe not to immediately prescribe antibiotics, advising no antibiotics but to return if symptoms do not resolve, rather than delayed antibiotics, will result in lower antibiotic use. However, patient satisfaction may be greater when a delayed prescribing strategy is used. Using a delayed antibiotic strategy will still result in a significant reduction in antibiotic use compared to the use of immediate antibiotics. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
+The review focuses on the effects of lubeluzole, an inhibitor of excitatory amino acids. The review of trials did not find any benefit of lubeluzole in humans either to prevent death after acute ischaemic stroke or to reduce disability from it. Moreover, lubeluzole may cause heart-conduction disorders.
+We searched for all randomised controlled trials (RCTs) that looked at the effects of any treatment to prevent CIP/CIM in adults admitted to an ICU. We identified and analysed five trials that were suitable for inclusion in our review. These trials studied four treatments: intensive insulin therapy (IIT), corticosteroid therapy, early rehabilitation, and electrical muscle stimulation. Two trials, with a total of 825 adults staying in ICU for one week or more, studied the effect of IIT versus conventional insulin therapy (CIT) on the incidence of CIP/CIM. IIT aimed to produce normal blood sugar levels (80 to 110 mg/dL) and CIT aimed to avoid high blood sugar (blood sugar over 215 mg/dL). Combining the results of both trials showed moderate quality evidence that IIT reduces CIP/CIM. There was high quality evidence that it reduced time spent on a ventilator, ICU stay and 180-day mortality but not 30-day mortality. There were more episodes of low blood sugar with IIT. Although there was not an increase in deaths within 24 hours of episodes of low blood sugar, low blood sugar remains a concern as it can damage the brain. Neither trial reported the degree of limb weakness or on physical rehabilitation. The results came from a subgroup of people who were in the ICU for a long time, which may also limit the conclusions. The third trial compared corticosteroid therapy with a placebo in 180 people with acute respiratory distress syndrome (ARDS). Moderate quality evidence suggested no effect of corticosteroids on CIP/CIM (in 92 participants evaluated). High quality evidence showed no effect on 180-day mortality, new serious infections, blood glucose levels on day seven or episodes of suspected or probable pneumonia. There were fewer episodes of shock (a life-threatening condition where there is a lack of blood flow to vital organs). The fourth trial was of on early rehabilitation in 104 participants in a medical ICU. There was moderate quality evidence of a reduction in CIP/CIM in the 82 participants who could be evaluated in the ICU. This effect was not significant when imputation to intention-to-treat analysis was performed. Early rehabilitation reduced the duration of mechanical ventilation but did not affect ICU stay or deaths. The trial reported no serious adverse events. Finally, a trial compared the effect of EMS of the lower limbs to no stimulation. The trial included 140 participants but provided results for only 52 of them. It supplied very low quality evidence that EMS was without effect in preventing CIP/CIM. There was no effect on duration of mechanical ventilation or deaths. Because the EMS and control groups differed in type and severity of disease,   these findings may not be reliable. Results were even less significant when imputation to intention-to-treat analysis was performed. The study found no effect of EMS on duration of mechanical ventilation or deaths. The evidence is up to date as of October 2011. We re-ran the search for studies in December 2013 and identified nine additional potentially eligible studies that we will assess in the next update of the review.
+Study characteristics: We found five studies, and we asked the study authors for more information. Three studies compared milrinone versus levosimendan, one study compared milrinone versus placebo, and one compared milrinone versus dobutamine. The patients were given the study drugs for 24 to 48 hours and were watched for six to 78 days. A total of 393 participants were included. Quality of evidence: Thus, the data are from a limited number of small trials and therefore must be viewed with caution. In addition, it was not always clear that the patient groups were formed and treated in a way that would make them completely comparable, that patients stayed in the trial for complete assessment, or that all study results were reported conscientiously. Key results: In one study comparing two doses of milrinone and placebo, milrinone was better than placebo to prevent reduced heart function within 36 hours after surgery, but there was not enough information about long-term heart function beyond the first postoperative days. It was not shown whether milrinone was better than placebo or than any of the other medications to prevent death, or whether the intensive care unit stay or hospital stay or time on mechanical ventilation was shorter if patients received milrinone. Similarly, when examining the studies regarding side effects of milrinone, we could not prove that milrinone caused more heart rhythm disturbances than dobutamine or placebo, or how it affected heart rhythm compared with levosimendan. We could not generate other useful information from comparing the trials regarding other harms which had been previously ascribed to milrinone, such as high heart rate, low blood pressure, bleeding into the brain's ventricular fluid, low potassium level in the blood, narrowing of the airways, low numbers of platelets in the blood, altered liver function tests, or low measurements of heart function by ultrasound. This was in part due to the different trial designs.
+This review of trials looked at which type of these medications, oral-form or injection-form, were the best in producing the most successful outcome. The review found no significant benefit of using one type of medication (oral or injectable) over the other, although there were insufficient data from trials. More research is needed to examine this question.
+In this review, we included three studies that investigated effects of aripiprazole. Two were short-term (eight weeks) studies that evaluated whether aripiprazole improved behavioural problems in a total of 316 children/adolescents. The third was a longer-term (up to 16 weeks) study in which 85 children/adolescents whose symptoms initially improved on aripiprazole discontinued the medication to evaluate whether their behavioural problems recurred. All participants were between six and 17 years of age. All studies used multiple behavioural checklists to assess symptoms of ASD. Short-term studies found improved irritability, hyperactivity and stereotypy (i.e. repetitive behaviours) and inappropriate speech in children/adolescents with ASD taking aripiprazole as compared with placebo. Researchers found no improvement in lethargy/withdrawal (i.e. lack of energy and reduced alertness). White children/adolescents were less likely to relapse (return to older, problematic behaviours) when taking aripiprazole, but this finding was not reported in children/adolescents of other races. Rates of movement disorder side effects such as tremor, muscle rigidity and involuntary movement were higher in children/adolescents taking aripiprazole in all trials. Results of this review suggest that short-term use of aripiprazole may improve irritability, hyperactivity and repetitive movements in children/adolescents with ASD, although both weight gain and neurological side effects (e.g. involuntary movements of the face and jaw) can occur. Children and adolescents taking aripiprazole should be re-evaluated periodically to monitor improvements in ASD symptoms and side effects. Overall, the quality of this evidence is moderate. Since the time these studies were conducted, an updated version of the manual for diagnosing ASD and other conditions has been published. Additional studies evaluating safety and benefits of long-term use of aripiprazole would be helpful.
+The review found promising evidence for the use of Chinese herbal medicine in reducing menstrual pain in the treatment of primary dysmenorrhoea, compared to conventional medicine such as NSAIDs and the oral contraceptive pill, acupuncture and heat compression. No significant adverse effects were identified in this review. However the findings should be interpreted with caution due to the generally low methodological quality of the included studies.
+We included 16 trials with 2084 participants. Thirteen trials carried out tests with selenium while three trials examined selenium-containing compound ebselen. Overall quality of the included trials was poor, with little information on quality indicators. The results were limited and these trials involving selenium supplementation were mostly small. In most trials, there was a high risk of poor or even incorrect information. Thus the results must be interpreted with caution. The evidence is current to 21 May 2014. Thirteen trials of intravenous sodium selenite showed a statistically significant effect on death. Three trials of the selenium-containing compound ebselen showed no effect on death. No effects on infections or secondary diseases were observed. No clear evidence emerged for the benefits of selenium or ebselen supplementation for days on a respirator, length of intensive care unit stay, length of hospital stay or quality of life. Due to the quality of included trials, one must be cautious when interpreting the strength of the evidence in favour of selenium supplementation despite a statistically significant finding. Overall, there was low quality evidence from the studies for the all results. Trials are required which overcome the statistical uncertainty of the reviewed studies, particularly in relation to sample size, design and outcomes.
+The review aims to compare a high-potency first-generation antipsychotic, perphenazine with low-potency first-generation antipsychotics. A search for trials was run in 2010. Four trials that randomised a total of 365 people are included. The studies compared perphenazine with chlorpromazine, thioridazine and levomepromazine. Overall, the trials were of poor quality, poorly reported and small scale. Review authors also rated the quality of evidence for the main outcomes to range from moderate to very low quality. It was found that perphenazine was not obviously clinically superior to low-potency first-generation antipsychotic drugs but was more likely cause the movement disorder akathisia (inner restlessness and the inability to sit still). Low-potency first-generation antipsychotics are thought more likely to cause side effects such as sedation and hypotension but evidence from this review showed people taking perphenazine were just as likely to experience hypotension as those taking first-generation antipsychotics and no data were available for sedation. Other outcomes, such as re-hospitalisation, costs, healthy days and quality of life were not addressed in the studies. No firm conclusions can be made about perphenazine's superiority or inferiority over low-potency first-generation antipsychotics until newer and better conducted studies are completed. This plain language summary has been written by a consumer, Benjamin Gray, from Rethink Mental Illness.
+This review included nine studies with a total of 1354 participants. One study reported improvement in urinary albumin levels following use of thiamine. None of the other studies reported improvement in kidney function or reduction in urinary albumin excretion after two to 36 months monotherapy with vitamin B therapy. Vitamin B therapy was reported to well-tolerated with mild side effects in studies with treatment duration of more than six months. Studies of less than six months duration did not explicitly report adverse events; they reported that the drugs were well-tolerated without any serious drug related adverse events. All these findings require confirmation in larger studies before they can be accepted as definite.
+This review includes four small studies which compare omega-3 supplements to placebo. In total there were 91 participants, including both children and adults. The studies lasted between six weeks and six months. One six-week study reported that lung function and clinical status improved when taking omega-3 supplements. Volunteers also produced less sputum when taking omega-3 supplements. Two longer studies found that people taking omega-3 supplements showed definite increases in levels of essential fatty acids in their white blood cell membranes and also in levels of phospholipids (molecules that provide structure and protection to cells) measured in blood samples. Few side effects were reported in any of the studies. We conclude that regular omega-3 supplements may benefit people with cystic fibrosis with few side effects. However, there is not enough evidence from the four small studies included in this review to draw firm conclusions or recommend the routine use of these supplements in people with cystic fibrosis. Larger and longer trials are needed to assess the clinical benefit of omega-3 supplementation and to determine the appropriate dosage. We do not think there are any factors in the way the studies were run which will influence the results in a negative way. It was not clear if these studies had any other risk of bias which might affect the results.
+We looked for research up to 13 May 2013 and included 33 trials in our analyses. Twenty-two trials compared outcomes for children given a lactose-free feed with those for children given a lactose-containing feed and 11 trials compared outcomes for children fed a diluted milk feed with those for children given an undiluted milk feed. We found evidence that feeds that do not contain lactose may reduce the duration of diarrhoea by an average of about 18 hours (low quality evidence). Lactose-free feeds probably lower the risk of children having prolonged or worsening diarrhoea (moderate quality evidence). We did not find any evidence that diluted milk feeds reduce the duration of diarrhoea (low quality evidence) but these feeds may lower the risk of children having prolonged or worsening diarrhoea (low quality evidence). The majority of trials excluded breast fed infants, and none were conducted in low-income countries where diarrhoea can cause death, so the review is relevant to infants and young children who are receiving formula or are weaned in high- and middle-income countries.
+We searched for evidence on 28 May 2017 and found three trials which met the inclusion criteria for the review. Participants in the trials were women after birth following a pregnancy of at least 24 weeks' gestation with a diagnosis of PPH, regardless of whether they had a vaginal or caesarean section. We identified three trials (involving 20,412 women). However, one of the trials (based in Iran) did not report important outcomes, therefore, our findings are based on two trials (involving 20,212 women) conducted in hospital settings in high-, middle- and low-income countries. One was a large trial that included more than 20,000 women, and both studies looked at the effectiveness and safety of intravenous (IV) TXA compared with placebo (dummy treatment) or no treatment. In both trials TXA was given in addition to usual care to treat bleeding. The trial contributing most of the information to the review was at low risk of bias. Our results show that TXA reduces the risk of maternal death due to bleeding (quality of evidence: moderate). There were fewer deaths from all causes but the findings were uncertain (quality of evidence: moderate). In one trial with a small sample size additional blood loss of 500 mL or more was also reduced (151 women; quality of evidence: low). TXA had little or no effect on the risk of serious maternal illness (quality of evidence: high), or complications such as stroke or deep venous thrombosis (quality of evidence: moderate). Rates of hysterectomy to control bleeding (quality of evidence: high) and blood transfusion (quality of evidence: moderate) were similar for women receiving TXA versus placebo. There was an increase in one surgical intervention (brace sutures) in the TXA group and a reduction in another (laparotomy to control bleeding) but there were no clear differences between groups for other surgical and invasive procedures. TXA when administered intravenously was effective in reducing mortality due to bleeding when given within three hours in women with primary postpartum haemorrhage without increasing the risk of other complications. Facilities for IV administration is not available in some settings so future research could look at whether TXA is effective and safe if given by other methods.
+Psychotherapeutic approaches, mainly cognitive behavior therapy, and antidepressant medication are the two treatment modalities that have received most support in controlled outcome studies of bulimia nervosa. Using a more conservative statistical approach, combination treatments were superior to single psychotherapy. This was the only statistically significant difference between treatments. The number of trials might be insufficient to show the statistical significance of a 19% absolute risk reduction in efficacy favouring psychotherapy or combination treatments over single antidepressants. Psychotherapy appeared to be more acceptable to subjects. When antidepressants were combined with psychological treatments, acceptability of the latter was significantly reduced.
+This review looked for all studies where patients were randomized to one or more treatments to measure the effects of such therapies. The questions of the review were to see whether drug treatments affected death or cardiovascular morbidity or whether there were differences between drug treatments. The available evidence was insufficient to answer these questions.
+We reviewed 23 studies with 2806 people with insomnia. Overall, the quality of the evidence was low due to a small number of people in the studies, and problems with how the studies were undertaken and reported. We often could not combine the individual study results. There was low quality evidence to support short-term (i.e. weeks rather than months) use for some antidepressants. There was no evidence for the antidepressant amitriptyline, which is commonly used in clinical practice, or to support long-term antidepressant use for insomnia. The evidence did not support the clinical current practice of prescribing antidepressants for insomnia. High quality trials of antidepressants for insomnia are needed to provide better evidence to inform clinical practice. Additionally, health professionals and patients should be made aware of the current paucity of evidence for antidepressants commonly used for insomnia management.
+Four studies involving 1265 women were included in our meta-analysis to compare HDR and LDR ICBT. The pooled results indicated there were no significant difference with regard to 3-, 5- and 10-year overall survival rates; 5- and 10-year disease-specific survival rates; 3- and 5-year relapse-free survival; 3- and 5-year local control rates; and local and distant recurrence. Only in respect to complications did HDR ICBTshow mildly increased numbers of small bowel complications. These results confirmed that there were no significant differences in the efficacy and safety of HDR versus LDR ICBT for women with locally advanced uterine cervical cancer. We included three randomised controlled trials and one quasi-randomised controlled trial. The way that randomisation was carried out was described in only two trials but they did not give details regarding allocation concealment and blinding. However, all trials had a low risk bias for incomplete outcome data (attrition bias) and selective reporting (reporting bias). The different methodological approaches used in the trials prevented any clear conclusion being reached regarding the quality of the evidence. According to GRADE, the quality of the evidence was low to moderate.
+We found 20 randomised controlled trials that tested ways to help people to cut down the number of cigarettes they smoked. Some of these just advised smokers to smoke less, but most also provided them with a product to help them cut down: nicotine replacement therapy (NRT), varenicline, bupropion, electronic cigarettes (ecigs), or snus (a form of smokeless, oral tobacco). We also found four randomized controlled trials that tested the effects of using cigarettes designed to reduce the damage caused by smoking: reduced tar, carbon or nicotine cigarettes. Most of the studies used NRT to help people to reduce their smoking. All of the studies included people who were not planning to quit smoking soon. The research is current to October 2015. Eight studies (with 3081 smokers) found that using NRT roughly doubled the likelihood of halving the number of cigarettes smoked each day, compared to using a placebo. Using NRT in this way also nearly doubled the likelihood of quitting completely. One trial each tested bupropion, varenicline, ecigs and snus to help reduce the harms caused by smoking, and there was no evidence that any of these treatments helped smokers to reduce the number of cigarettes they were smoking each day. This may be because there has not yet been enough research into these methods. Only one of the trials testing cigarettes designed to reduce risk measured their effect on the number of people quitting smoking. It found that people were not more likely to quit smoking if they used reduced-nicotine cigarettes than if they smoked their usual cigarettes. We did not find any trials which reported the long-term health effects of the treatments, and so it remains uncertain how much health benefit there is from reducing the number of cigarettes smoked each day or smoking cigarettes designed to be less harmful. The tobacco industry funded three of the included studies of cigarettes designed to reduce risk. None of the studies looked at whether there had been a long-term change in the health of the users. We rate the quality of the evidence looking at how many people quit smoking as 'low' or 'very low', generally because the findings are based on a small number of studies. We need more studies to investigate methods of reducing the harm caused by continued smoking. These need to measure the health of the users over a long period.
+Cochrane researchers searched the available evidence up to 30 August 2015 and included 35 trials (31,955 children). Iron did not increase the risk of malaria, indicated by fever and the presence of parasites in the blood (high quality evidence). There was no increased risk of death among children treated with iron, although the quality of the evidence for this was low. Among children treated with iron, there was no increased risk of severe malaria (high quality evidence). Although it is hypothesized that iron supplementation might harm children who do not have anaemia living in malarial areas, there is probably no increased risk for malaria in these children (moderate quality evidence). In areas where health services are sufficient to help prevent and treat malaria, giving iron supplements (with or without folic acid) may reduce clinical malaria. In areas where these services are not available, iron supplementation (with or without folic acid) may increase the number of children with clinical malaria (low quality evidence). Overall, iron resulted in fewer anaemic children at follow up, and the end average change in haemoglobin from base line was higher with iron. Our conclusions are that iron supplementation does not adversely affect children living in malaria-endemic areas. Based on our review, routine iron supplementation should not be withheld from children living in countries where malaria is prevalent and malaria management services are available.
+This review of trials found that giving naloxone to people in shock improves their blood pressure. It is not clear whether or not this improves their overall condition or reduces their chances of dying. More trials are needed.
+We included seven randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method) that compared the effects of immunoglobulins with placebo in 486 young children hospitalised with RSV lung infections. All trials were conducted at sites in the USA; three trials included some children from South American countries (Chile and Panama); and one trial also included children from New Zealand and Australia. The trials were published between 1987 and 2014. Five trials were supported by the manufacturer of the immunoglobulin tested in the studies. One trial was supported by a government agency, and one trial did not describe how it was funded. Immunoglobulins did not appear to be more effective than placebo in preventing deaths among young children with RSV infection, although few deaths occurred in the trials. Immunoglobulins given to children hospitalised with RSV lung infection did not decrease the time spent in hospital. Children treated with immunoglobulins experienced adverse effects of any severity or seriousness and adverse effects considered to be serious (such as respiratory failure) as often as children treated with placebo. There was no difference between immunoglobulins and placebo for any other outcomes measured in the trials, such as the need for oxygen or admission to the intensive care unit. Data from populations in which the rate of death from RSV infection is higher are lacking. The quality of the evidence was low or very low, which means that the true effect of immunoglobulin treatment for young children in hospital with RSV lung infection may be very different from the findings of this review.
+In total we included 25 RCTs and 3096 participants in this review update. Only one trial included patients with acute LBP (pain duration less than four weeks), while all the others included patients with sub-acute (four to 12 weeks) or chronic LBP (12 weeks or longer). In three studies, massage was applied using a mechanical device (such as a metal bar to increase the compression to the skin or a vibrating instrument), and in the remaining trials it was done using the hands. Pain intensity and quality were the most common outcomes measured in these studies, followed by back-related function, such as walking, sleeping, bending and lifting weights. Seven studies did not report the sources of funding, Sixteen studies were funded by not-for-profit organizations. One study reported not receiving any funding, and one study was funded by a College of Massage Therapists. There were eight studies comparing massage to interventions that are not expected to improve outcomes (inactive controls) and 13 studies comparing massage to other interventions expected to improve outcomes (active controls). Massage was better than inactive controls for pain and function in the short-term, but not in the long-term follow-up. Massage was better than active controls for pain both in the short and long-term follow-ups, but we found no differences for function, either in the short or long-term follow-ups. There were no reports of serious adverse events in any of these trials. The most common adverse events were increased pain intensity in 1.5% to 25% of the participants. The quality of the evidence for all comparisons was graded "low " or "very low" which means that we have very little confidence in these results. This is because most of the included studies were small and had methodological flaws.
+We identified a single high quality trial with a total of 38,546 participants, comparing vaccination with placebo. It found a significant reduction of herpes zoster, but did not provide enough direct evidence to draw any conclusion about whether the vaccine is effective in preventing postherpetic neuralgia beyond its effect on reducing herpes zoster. Non-serious adverse events were more common among vaccine recipients than placebo recipients, but serious ones were rare. More well designed and specialised trials of vaccination for preventing postherpetic neuralgia are required.
+This review included 61 trials (12,192 participants). Fifty-eight trials compared corticosteroids to no corticosteroids (placebo or usual care in 48 and nine trials, respectively); three trials also compared continuous versus bolus administration of corticosteroids. Three trials were funded by a drug company, 27 by public organizations or through charitable funding, and six by both a drug company and public organizations or charitable funding; 25 did not declare the source of funding. We have analysed the following two comparisons. • Corticosteroids versus placebo/usual care. Corticosteroids probably reduce the risk of death at 28 days by 9% (50 trials; 11,233 participants), with consistent treatment effects between children and adults. They also probably slightly reduce the risk of dying in hospital. There may be little or no effect of corticosteroids on risk of dying over the long term (longer than three months), but these results are less certain. Corticosteroids result in a large reduction in length of stay in the intensive care unit (ICU) and in hospital. Corticosteroids increase the risk of muscle weakness and hypernatraemia. They probably increase the risk of hyperglycaemia. They probably do not increase the risk of superinfection. There may be little or no effect of corticosteroids on risk of gastroduodenal bleeding, neuropsychiatric events, stroke, or cardiac events. • Continuous infusion versus intermittent boluses of corticosteroids. We are uncertain about the effects of continuous infusion of corticosteroids compared with intermittent bolus administration. Three studies reported data for this comparison, and the certainty of evidence for all outcomes was very low. • Corticosteroids versus placebo/usual care We judged the certainty of evidence for 28-day mortality as moderate due to some inconsistency related to differences among study populations, types of corticosteroids and how they were given, and use of additional interventions. • Continuous infusion versus intermittent boluses of corticosteroids We judged the certainty of evidence for 28-day mortality as very low due to inconsistency and imprecision.
+This review found some trials comparing the effects of adding second-generation antipsychotic drugs or placebo to antidepressants in obsessive compulsive disorder. There were only 11 trials on three second-generation antipsychotic drugs (olanzapine, quetiapine and risperidone). While not much can be said about olanzapine, quetiapine and risperidone showed some efficacy benefit, but also adverse effects.
+In animal studies, the drug tirilazad appeared to reduce brain damage after SAH. We reviewed the evidence from randomised controlled trials of tirilazad in patients with SAH to see if it could reduce the risk of death or disability. The review did not show any evidence of benefit from tirilazad in patients with aneurysmal SAH.
+Six trials (807 donors) were identified for this review. The review found that donors donating via a bone marrow harvest experienced more pain at the donation site (hip bone area) in the days following the donation, more days of restricted activity (e.g. sick days), more days in hospital and more side effects than donors donating through a peripheral blood stem cell harvest. In contrast, peripheral blood stem cell harvest donors experienced more pain prior to the donation of blood stem cells than bone marrow harvest donors. This pain was as a result of G-CSF administration. All donors had increased levels of tiredness and reduced levels of energy and anxiety following their donation. There were three main limitations of this review. Firstly, in two trials more than 40% of the donors did not complete the trial. Secondly, there was no long-term follow up of the donors in any trial. Thirdly, the trials used different questionnaires to record the donors emotional experience of the donation procedure which made it difficult to compare the results of these measurements across the six trials. Further research, with larger numbers of included donors, would provide a greater understanding of the donation experience.
+A search for trials was carried out in July 2012. The review now includes seven studies with a total of 479 participants and assesses the effects of perazine for people with schizophrenia. Comparisons of perazine versus placebo (‘dummy’ treatment) and versus other antipsychotic drugs revealed no clear differences or superiority of perazine. However, only a handful of studies have been undertaken and the number of participants in each study was small. In addition the studies avialable were of limited quality with data for the main outcomes of interest rated as low or very low quality. As perazine is a cheap drug and there is some limited evidence that it may cause less side effects than other older antipsychotic drugs, further large scale, well designed and well-reported studies are much needed. This plain language summary has been written by a consumer Benjamin Gray from Rethink Mental Illness, Email: [email protected].
+We searched the medical literature for eligible studies through June 2016. We found four studies that compared antibiotics versus placebo for reducing infection among babies born with meconium-stained amniotic fluid. Two studies were of good quality, and two studies were missing some details regarding study methods. These four studies included 695 babies, who were given various antibiotics or were placed in the control group (no antibiotics). Researchers evaluated several different antibiotic types and treatment lengths. Overall, we found no differences in rate of infection or death between the two groups. We graded the evidence as low quality owing to a poor quality study design and the small number of included babies. We are uncertain as to whether antibiotics have an important effect on infection in babies exposed to meconium-stained amniotic fluid. Our results are imprecise, and more studies are needed to determine the role of antibiotics in this situation.
+This systematic review focused on (randomised) controlled studies. The authors found that there were no studies in which the only difference between the intervention and control group was the use of MTX. They did identify a RCT comparing MTX with cisplatin. The risk of bias in this study was difficult to assess due to a lack of reporting. Survival could not be evaluated, but no evidence of a significant difference in response rate between the treatment groups was identified. However, a significant difference in the occurrence of toxicities in favour of treatment with MTX was identified, but treatment with cisplatin seemed to give better results with regard to quality of life. It should be noted that this study was performed in a different treatment era. Nowadays single agent treatment of osteosarcoma is considered inadequate. For other combinations of treatment including and not including MTX no studies are available. More high quality research is needed. At the moment, the authors are awaiting more details on 5 studies for which the currently available data were insufficient to assess eligibility for inclusion in this review.
+We did computer searches for all published randomized trials that compared different methods of cervical preparation before second-trimester D&E and we found six studies that met our criteria. All of the methods compared were different from one another, thus it was not possible to combine data from multiple studies. We looked at how these preparation methods compared with respect to safety, procedure time, need for additional dilation, ability to perform the procedure, and patient and provider acceptability. We found that all methods reviewed were safe. Certain dilators called laminaria appeared to result in more cervical opening (dilation) than the prostaglandin medications, however no difference was seen between dilators and prostaglandins with respect to safety, length of procedure, or the ability to complete the procedure. We found that when mifepristone, a medication that blocks the action of a hormone called progesterone, was used with a prostaglandin called misoprostol that many women ended up expelling the pregnancy before their desired surgical procedure. Due to this increased rate of expulsions prior to planned D&E, we feel that the combination of mifepristone and misoprostol should not be used for cervical preparation when women are desiring a surgical procedure instead of an induction. We found that one day of cervical preparation is just a good as two days and that same-day cervical preparation appears to be safe in the early part of the second trimester. We believe that more research is needed in the area of same-day cervical preparation as it is much easier for women to have a one-day instead of a multiple day procedure. We also think more research is needed in the area of combining prostaglandins with dilators as this may improve the possibility of conducting same-day procedures later into the second trimester.
+This review included 53 randomised controlled trials comparing these interventions to various control groups (mostly usual standard sex education offered by schools). The search for trials was not limited by country, though most of the included trials were conducted in high-income countries, with just four trials in middle- and low-income countries, mainly representing the lower socio-economic groups. Interventions were administered in schools, community centres, healthcare facilities and homes. Meta-analysis was performed for studies where it was possible to extract data. Only interventions involving a combination of education and contraception promotion (multiple interventions) was seen to significantly reduce unintended pregnancy over the medium-term and long-term follow-up period. Results for behavioural (secondary) outcomes were inconsistent across trials. Limitations of this review include reliance on programme participants to report their behaviours accurately and methodological weaknesses in the trials.
+The review assessed whether routine antibiotic treatment after uncomplicated vaginal birth, compared with either placebo or no antibiotics, prevents maternal infection. We searched for evidence in August 2017 in three databases. We identified three trials involving 1779 women. The quality of the evidence ranged from low to very low. Different antibiotics were administered in the three trials and for different lengths of time. The trials took place in the 1960s (one trial) and 1990s (two trials), and were carried out in France, the USA and Brazil. Routine antibiotic administration reduced the number of women with infection of the lining of the uterus (endometritis) (2 trials, 1364 women) by 70%. The use of antibiotics did not reduce the incidence of urinary tract infections (2 trials, 1706 women), wound infections after episiotomy (2 trials, 1364 women) or length of maternal hospital stay (1 trial, 1291 women). There were no differences between the groups for skin rash due to antibiotics, reported in one woman in each of the two trials (1706 women). The cost of care was higher in the group that did not receive antibiotic prophylaxis. The incidence of severe maternal infections and illness, antimicrobial resistance or women's satisfaction with care were not addressed. The small number of trials limits the interpretation of the evidence for routine use of antibiotics after normal vaginal births. The low incidence of endometritis in the studies suggests that a relatively large number of women may have to be treated to avoid a few case of infection. There needs to be a balance between women's needs, childbirth setting and provider experience (for example, with frequent vaginal examinations or interventions) and the public health threat of antibiotics resistance. Further research from well-designed randomised controlled trials would help to evaluate the added value of routinely giving women antibiotics after normal vaginal birth to prevent maternal infections.
+Although some of the studies did favour acupuncture when combined with antipsychotics, the information available was small scale and rated to be very low or low quality by the review authors, so not completely provable and valid. Depression was reduced when combining acupuncture with antipsychotic medication, but again this finding came from small-scale research, so cannot be clearly shown to be true. The review concludes that people with mental health problems, policy makers and health professionals need much better evidence in order to establish if there are any potential benefits to acupuncture. This means that the question of whether acupuncture is of benefit to people, and whether it is of greater benefit than antipsychotic medication, remains unanswered. There is not enough information to establish that acupuncture is of benefit or harm to people with mental health problems. Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness.
+We identified three studies meeting our quality criteria for inclusion in the review. All had methodological limitations meaning that we could not draw firm conclusions. With respect to the primary outcomes, they showed ambiguous results for overall mortality when comparing treatment arms: one study favored transplantation and two studies favored treatment with ciclosporin and/or antithymocyte or antilymphocyte globulin. Treatment-related mortality, that is death caused by complications of the treatment, was considerable for patients in the transplantation arm. Treatment failure, that is no response to treatment, was substantial for patients in the ciclosporin and/or antithymocyte or antilymphocyte globulin arm. Graft failure was reported for 3% to 16% and graft-versus-host-disease for 26% to 51% of the transplanted patients. Because the data are scarce and biased it is not possible to determine which treatment is better - transplantation for HLA-matched sibling donors or ciclosporin and/or antithymocyte or antilymphocyte globulin for patients that do not have such a sibling. Several reasons make it highly probable that there will not be any good evidence comparing these interventions in the future. One reason is that randomized controlled trials are unlikely to be conducted due to ethical constraints and strong patient and clinician preferences. Studies with 'Mendelian randomization' could provide some good evidence in theory, however, in practice they are difficult to conduct properly and have been disappointing. 'Mendelian randomization' means the view that nature itself has already 'randomized' the paternal and maternal part of a gene given that donor and recipient are siblings. Another reason is that the outcome of transplantation has improved considerably. This is true for matched donor transplantation including both related and unrelated donors. It means that ciclosporin and/or antithymocyte or antilymphocyte globulin may not be a first treatment choice if a matched sibling or even a matched unrelated donor is available.
+This Cochrane Review summarises trials evaluating the effects of artemisinin-naphthoquine compared to other artemisinin-based combination therapies (ACTs) recommended by the World Health Organization (WHO) for treating adults and children with uncomplicated P. falciparum malaria. After searching for relevant trials up to January 2015, we included four randomized controlled trials, enrolling 740 adults and children. What is uncomplicated malaria and how might artemisinin-naphthoquine work Uncomplicated malaria is the mild form of malaria which usually causes a fever, with or without headache, tiredness, muscle pains, abdominal pains, nausea, and vomiting. If left untreated, uncomplicated malaria can develop into severe malaria with kidney failure, breathing difficulties, fitting, unconsciousness, and eventually death. The WHO recommends ACT for treating people with P. falciparum malaria. Five combinations are currently recommended, all administered over three days. Artemisinin-naphthoquine is a new combination developed in China, which is being marketed and evaluated as one-day or three-day regimens. What the research says Artemisinin-naphthoquine versus artemether-lumefantrine In three small trials from Benin, Côte d'Ivoire, and Papua New Guinea, both artemisinin-naphthoquine and AL had a very low incidence of treatment failure at Day 28 (low quality evidence), and in the trial from Papua New Guinea it remained low in both groups at Day 42 (very low quality evidence). Artemisinin-naphthoquine versus dihydroartemisinin-piperaquine In a single small study from Indonesia, treatment failure at Day 28 and Day 42 was very low with both artemisinin-naphthoquine and DHA-P (very low quality evidence). Conclusions The results of these few trials of artemisinin-naphthoquine are promising, but larger trials from multiple settings are required to be confident that artemisinin-naphthoquine is as effective and well tolerated as other antimalarials.
+In January 2016 we searched for clinical trials where fentanyl was used to treat neuropathic pain in adults. We found one small study that did this and met our requirements for the review. The study had a complicated design. Study participants first received fentanyl (as one-day skin patches) for one month. Those who responded to therapy (achieved a predetermined level of pain relief) were then randomly allocated to continue receiving fentanyl or placebo for 12 weeks. The participants had one of three different types of neuropathic pain and had not taken opioids before. There were only 163 people in the 12-week comparison with placebo. The study found that more people taking fentanyl had pain relief than those taking placebo. About 1 in 7 participants stopped taking fentanyl because of side effects, and 1 in 5 did not get a good level of pain relief in the first part of the study. Almost half of those who continued into the second part of the study also stopped. The most common side effects were constipation, nausea (feeling sick), somnolence (feeling sleepy), and dizziness. These are typical side effects with opioids such as fentanyl. There was so little information from this single study that we concluded there was no convincing evidence to support or reject a meaningful benefit for fentanyl over placebo. We rated the quality of the evidence as very low because there was only one study, with few participants and events, and an unusual design. Very-low-quality evidence means that we are very uncertain about the results.
+The studies looked at people who had rheumatoid for up to 2 years. Low doses of glucocorticoid pills were taken and usually with a disease-modifying anti-rheumatoid drug (DMARD). Glucocorticoids reduce progression of the disease on x-rays over 1 to 2 years. This result is based on high quality evidence. Harms were not reviewed. We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects and long term side effects. Low doses of glucocorticoids may not lead to side effects, but possible side effects may include osteoporosis or heart problems.
+Studies were short, mostly between two and12 weeks, with only one of 18 weeks. The studies involved 1804 mainly healthy adults. They provided participants with 30 to 1218 mg of flavanols (average of 670 mg) in 1.4 to 105 grams of cocoa products per day in the active intervention group. Seven of the studies were funded by companies with a commercial interest in their results, and the reported effect was slightly larger in these studies, indicating possible bias. The evidence is current to November 2016. Meta-analysis of 40 treatment comparisons revealed a small but statistically significant lowering of blood pressure (systolic and diastolic) of 1.8 mmHg. This small reduction in blood pressure might complement other treatment options and might contribute to reducing the risk of cardiovascular disease. We investigated whether participants' blood pressure at the start of the study, their age, an awareness of group allocation (active or control), the flavanol content used in the control group, or how long the study lasted may explain variations between trials. While blood pressure status (high blood pressure or normal blood pressure) is a likely factor in the effect size of cocoa on blood pressure, the impact of other factors needs to be confirmed or rejected in further trials. Side effects including digestive complaints and dislike of the trial product were reported by only 1% of people in the active cocoa intervention group and 0.4% of people in the control groups. Longer-term trials are needed to establish whether regularly eating flavanol-rich cocoa products has a beneficial effect on blood pressure and cardiovascular health over time, and whether there are any side effects of long-term use of cocoa products on a daily basis. The evidence is of moderate quality. We were unable to identify any randomised controlled trials that tested the effect of long-term daily use of cocoa products on blood pressure, and there were no trials that measured the health consequences of high blood pressure, such as heart attacks or strokes.
+The review includes 13 trials with a total of 711 people with schizophrenia and other psychiatric diagnoses. Due to the poor quality, small size, and limited data from the 13 studies, there is limited evidence. It is not known if strategies such as dose reduction, ‘drug holidays’, and stopping medication are helpful in the treatment of tardive dyskinesia. There is limited evidence on specific antipsychotic drugs in the treatment of tardive dyskinesia. Evidence is poor, small scale, and of short duration. There is a need for larger trials of a longer duration in order to fully investigate this area. This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (http://mcpin.org/).
+We searched electronic databases and music therapy journals to identify relevant studies. We included six studies with a total of 314 participants. The studies compared the effect of listening to music alone or with standard care to standard care alone or no treatment. The studies examined the effect of listening to pre-recorded music daily, for 25 to 60 minutes, for a period of three days to five weeks.The evidence is current to 22 May 2015. Five studies measured sleep quality. The findings suggest that listening to music can improve sleep quality. Only one study reported data on other aspects of sleep, including the length of time it takes to fall asleep, the amount of actual sleep someone gets, and the number of times people wake up. This study found no evidence to suggest that listening to music benefits these outcomes. None of the studies reported any negative side effects caused by listening to music. The quality of the evidence from the five studies that examined sleep quality was moderate. The quality of evidence for the other aspects of sleep was low. More high quality research is needed to investigate and establish the effect of listening to music on other aspects of sleep than sleep quality and on relevant daytime measures.
+We updated the main database searches in March 2017. We identified four studies (571 women) for inclusion. The women primarily had cancer of the cervix and endometrium, with only one study also including women with cancer of the ovary. Our findings demonstrated that placement of suction drains is not effective in preventing lymphocysts, especially when the peritoneum (pelvic lining) is left open. In fact, such practice increases the risk of short- and long-term lymphocyst formation with related symptoms. The review includes four moderate to high quality evidence (unclear or low risk of bias) clinical trials in its final analysis.
+We searched the published literature for randomised clinical trials that evaluated intravesical gemcitabine in bladder cancer patients and found six trials. The first trial compared a single dose of gemcitabine with a placebo immediately following surgery and found no difference in the rate of tumour recurrence, although there was some concern over the trial methodology. Another study compared gemcitabine with the established anticancer drug mitomycin C and showed that gemcitabine was more active and less toxic. Three trials compared gemcitabine with intravesical BCG. The first enrolled patients with intermediate risk of recurrence and reported gemcitabine was as effective as BCG in preventing tumour recurrence and disease progression but with fewer side-effects. The second trial enrolled untreated patients with a high risk of recurrence and found gemcitabine to be inferior to BCG in preventing recurrence but again was less toxic than BCG. The third trial recruited patients who had previously received BCG but had not responded and this study showed that gemcitabine was superior to BCG in reducing the rate of tumour recurrence. These small numbers of trials indicate that intravesical gemcitabine has activity in delaying tumour recurrence and may have a role in patients who are not suitable for, or who have failed, BCG therapy. The final study suggested that multiple doses of gemcitabine gave better tumour responses compared to a single dose, although the clinical significance of this is unclear.
+A review of randomized (RCT) and controlled clinical trials (CCT), case-control and cohort studies of the use of ES in RA only identified two RCTs, only one of which met the criteria for retention. The results of this one RCT, involving 15 patients with RA affecting the hand, showed significant results that favoured the use of patterned ES derived from a fatigued motor unit from the first dorsal interosseous in a normal hand for all outcome measures: grip strength, pinch strength, and muscle function and endurance. Electrical stimulation whether delivered at a fixed frequency of 10 Hz or at patterned frequency, had significant benefit when compared to a no treatment control group on two outcome measures: pinch strength and muscle endurance. These conclusions however are limited by poor reporting of the characteristics of application of the ES and the poor methodological quality of the trial. The reviewers therefore conclude that there is no clear evidence for the inclusion of ES in the management of RA at this time.
+The review found only one randomised trial which assessed the effect of the timing of surgery. From the limited evidence available, the timing of surgery was not a critical factor in determining the outcome from an aneurysmal subarachnoid haemorrhage, but further research is needed.
+One trial was found that examined the effect of inotropes in infants with low systemic blood flow. The trial found that many infants failed to respond to the two commonly used inotropes (dobutamine and dopamine) and neither was better at improving outcomes of very preterm babies. Further research is needed to determine the best strategy for preventing or treating low systemic or organ blood flow in these very immature babies.
+We found only two small studies which were suitable to include in our review. In one study, the 58 patients who took part all had advanced cancer. They were treated in a specialist palliative care unit. The study compared lorazepam (a benzodiazepine) to placebo. In the second study, the 30 patients all had AIDS (acquired immune deficiency syndrome). They were treated in general medical wards. This study compared lorazepam to two different drugs that are sometimes used to treat delirium. We did not find any important benefits for patients who took lorazepam instead of the other treatment in these two studies. Patients who took it did not have better outcomes. We do not have any definite evidence that lorazepam was more harmful than the other treatment, but, in the study of patients with AIDS, the researchers stopped treating people with lorazepam after the first six people who took it all had serious side effects. Because there were only two suitable studies and both had small numbers of patients in them, we cannot draw any firm conclusions. Currently, there is no good evidence to tell us whether or not benzodiazepines should be used to treat patients with delirium. Clinicians, patients, and carers should be aware of the lack of evidence. We think there is a need for more research, and particularly for studies that involve older patients in general medical and surgical settings, where most delirium is treated.
+We searched for randomized studies enrolling people who smoked and were awaiting any type of planned surgery. The trials tested interventions to encourage and help them to stop smoking before surgery. Interventions could include any type of support, including written materials, brief advice, counselling, medications such as nicotine replacement therapy (NRT) or varenicline, and combinations of different methods. The control could be usual care or a less intensive intervention. We found 13 studies which met the inclusion requirements. The overall quality of evidence was moderate, limited by the small number of studies contributing to key analyses. Participants were awaiting a range of different types of surgery. Interventions differed in their intensity, and in how long before surgery they began. Both brief (seven trials, 1141 participants) and intensive (two trials, 210 participants) behavioural interventions were effective in increasing the proportion of smokers who were not smoking at the time they had surgery. The two trials using intensive interventions which started four to eight weeks before surgery had larger effects. Six trials of behavioural interventions assessed postoperative complications. Both trials of intensive interventions (210 participants) detected a reduction in complications in people receiving intervention, but the combined results of the four trials of brief interventions did not show a significant benefit. Only four trials of behavioural interventions followed up participants at twelve months. The two intensive interventions (209 participants) reduced the number of people smoking but the two brief interventions (341 participants) no longer showed a difference in the number of smokers. One trial of varenicline (286 participants), a pharmacotherapy shown to assist quitting in other groups of smokers, showed a benefit on cessation after twelve months, but did not show a benefit at the time of surgery or affect complications. In this trial smokers were only asked to stop the day before surgery.
+The review of 22 trials, involving 6872 women and their babies, found that, in the short term, certain antibiotics given to women, when their waters break early, increase the time babies stay in the womb. They reduced infection, but did not save more babies. One antibiotic (co-amoxiclav) increased the number of babies with a rare condition of inflammation of the bowel (necrotising enterocolitis). Although, in the longer term (at seven years of age) antibiotics seem to have little effect on the health of children, the short-term advantages are such that we recommend antibiotics should be given routinely.
+This review found 34 studies that have evaluated various types of GDL programs. All of the studies reported positive findings, with reductions for all types of crashes among all teenage drivers. However, the size of the reductions varied and, based on the included studies it is not possible to say which aspects of GDL programs have the biggest effect. Future research on GDL should evaluate the relative impact of different program components.
+The evidence is current to January 2017. We identified six studies with a total of 557 participants. The studies were blinded, placebo-controlled randomised trials that tested how effective the NTHi vaccine is in preventing infections in people over 18 years of age with COPD or chronic bronchitis. In all six trials, both the vaccine and placebo group were given at least three courses of tablets at regular intervals over a period of three to 12 months. Generally, the baseline demographics of participants across the included studies shared similar characteristics (such as diet, lifestyle, and living conditions) to other high-income countries. Ages ranged between 40 and 80 years. The studies counted the number of infections the participants experienced, levels of respiratory tract bacteria, deaths, side effects, hospital admissions, or treatment with antibiotics. The NTHi vaccine had no significant impact on reducing the number of acute exacerbations experienced by people with COPD. There was no significant difference in mortality rate between the vaccine and placebo groups, and the reported deaths in the vaccinated group were not attributed to the vaccine. The levels of H influenzae bacteria found in the respiratory tracts of participants did not differ between the vaccine and placebo groups. Due to inconsistencies of measurement between the trials, we were not able to compare the studies against one another. Antibiotics, which can be an indicator of severe infection, were significantly more commonly prescribed in the placebo group. Evidence of hospital admissions showed that there was no difference in the likelihood of being hospitalised in either the vaccine or the placebo group. Two trials studying quality of life found that vaccinated participants generally had a better quality of life, but these results were measured differently and so could not be compared. Five trials reported adverse effects, but there was no particular association with either the vaccine or placebo group. Further research is needed to define adverse effects as outcome measures for more definitive analyses regarding vaccine side effects. The studies were well conducted with moderate risk of bias. The main limitation of this review was the lack of consistency regarding the definitions and outcome measures among the individual studies, which affected the overall synthesis and interpretation of the results. Fewer participants may mean the results are more likely to be affected by chance. One trial had more participants than the other five trials combined, and it contributed more to the final analysis. There was moderate heterogeneity (the studies showed quite different results) when this study was included in the analysis, especially in numbers of infections. However, the results were consistent and did not change when this study was removed from the analysis. We concluded after reviewing the relevant studies that the H influenzae vaccine taken orally in people with chronic bronchitis and COPD does not have a significant reduction in the number and severity of acute exacerbations.
+This review includes 11 trials that tested the effectiveness and safety of various micronutrient supplements in children with HIV infection in a diversity of settings. All except one trial were conducted in African children. The primary outcomes were mortality, morbidity, and HIV-related hospitalisations, and secondary outcomes were HIV disease progession, measures of growth, and adverse effects of supplementation. The review found that vitamin A supplements are beneficial and safe, and halved mortality overall in an analysis of three trials in different African countries. Zinc appeared to be safe and reduced diarhoeal morbidity in one trial. Multiple micronutrient supplements reduced the duration of hospital admissions, and improved appetite and short-term growth in poorly nourished hospitalised children. Further research is needed on single supplements other than vitamin A, and on the long-term effects, optimal composition and dosing of multiple supplements.
+Fifteen studies of moderate to high quality were reviewed and provide the best evidence we have today. The studies tested almost 6000 people with osteoarthritis of the hip or knee. The studies compared people who took 4000 mg of acetaminophen (Tylenol, Paracetamol) a day to people who took a placebo (fake pill) or non-steroidal anti-inflammatory drugs (NSAIDs). Most studies lasted on average about 6 weeks.   What is osteoarthritis and what drugs are used to treat it?  Osteoarthritis (OA) is the most common form of arthritis that can affect the hands, hips, shoulders and knees. In OA, the cartilage that protects the ends of the bones breaks down and causes pain and swelling. There are two main types of drug treatments in OA: acetaminophen which is used to relieve pain but does not affect swelling; and NSAIDs, such as ibuprofen, diclofenac and cox IIs (celecoxib), which are used to decrease pain and swelling. It is not clear which type is best to use or which causes more side effects: high doses of acetaminophen may cause stomach problems, such as ulcers, and NSAIDs may cause stomach, kidney or heart problems.   What did the studies show?  Acetaminophen compared to placebo  The studies show that people who took acetaminophen has less pain (when resting, moving, sleeping and overall) and felt better overall than people who took a placebo. Pain (when measured on a different scale), physical function and stiffness were about the same.  • Pain decreased by 4 more points on a scale of 0-100 for people who took acetaminophen instead of a placebo.
+This review found data in three clinical trials, involving 1202 people with moderate or severe pain after having wisdom teeth removed or after abdominal or pelvic surgery. These situations are used commonly to test analgesic effectiveness, because results are applicable to other forms of acute pain after trauma. Different types of surgery give very similar estimates of the effectiveness of analgesic drugs. Ibuprofen 400 mg plus oxycodone 5 mg provided effective pain relief for about 6 in 10 (60%) of participants, compared with just under 2 in 10 (17%) of participants with placebo. The analgesic effects lasted longer and there were no more adverse events with the combination than with placebo. The combination provided effective pain relief to about the same proportion of people as did ibuprofen alone, but there was a lower chance of needing additional analgesia with the combination.
+In this review the effect of whole grain foods and cereal fibre (as a marker of whole-grain food intake) on the prevention of type 2 diabetes mellitus (T2DM) was assessed using all available prospective cohort studies and randomised controlled trials. Only one randomised controlled trial was found which was of low methodological quality. This study investigated in 12 overweight persons during six weeks the effect of the consumption of refined grain foods versus that of whole grain foods on insulin sensitivity (risk factor for the development of T2DM). Intake of whole grain foods resulted in a slight improvement of insulin sensitivity, increased bowel movements and no adverse effects. No information was given about patient satisfaction, health related quality of life, total mortality and morbidity. In addition eleven prospective cohort studies were found. One study was conducted in Finland and the rest in the United States of America of which seven were done in health care workers. Some of the studies were of limited quality. They consistently showed that a high intake of whole grain foods or cereal fibre is associated with a lower risk of the development of T2DM. However, evidence for a protective effect coming from prospective cohort studies only has to be considered as weak as with this design no cause and effect relationship can be established. Well-designed randomised controlled trials are needed to be able to draw definite conclusions about the preventive effects of whole grain consumption on development of T2DM.
+We included 19 randomised controlled trials (1870 participants) of premenopausal and postmenopausal women undergoing hysteroscopic surgery for a variety of conditions. They compared misoprostol with placebo or no treatment, dinoprostone, and osmotic agents. Key results There is moderate quality evidence that misoprostol is safer and is more effective for cervical ripening than placebo or no treatment, and that is associated with fewer complications occurring during the operation, with lower rates of lacerations and false tracks. However misoprostol is associated with more side effects such as preoperative pain and vaginal bleeding. There is low quality evidence that misoprostol may be safer and more effective than dinoprostone, and that it may be associated with fewer complications occurring during the operation. There is also low quality evidence that laminaria may be more effective than misoprostol. However, the possible benefits of laminaria need to be weighed against the inconvenience of its insertion and retention for one to two days. Quality of the evidence The quality of the evidence ranged from low to moderate. The main limitations in the evidence were imprecision and poor reporting of study methods. The evidence is current to August 2014.
+Only two studies met the inclusion criteria for this review. Both studies investigated the effect of adult education classes on the online health literacy of consumers. There is low quality evidence that these interventions improve aspects of online health literacy, specifically, regarding the outcomes 'self-efficacy for health information seeking', 'health information evaluation skills', 'number of times the patient discussed online information with a health provider' and 'readiness to adopt the internet as a tool for preventive health information'. No adverse effects were reported. As the study participants were, respectively, HIV-infected consumers, and people aged over 50, there is limited evidence on which to draw conclusions about the effect of these interventions on other population groups. More high quality studies on this topic are necessary.
+We searched medical databases for clinical trials of melatonin added to another antiepileptic drug (add-on treatment) compared with antiepileptic drug plus add-on pretend treatment (placebo) or add-on no treatment in people with epilepsy. The participants were of any age or sex and included children and adults with disabilities. The studies measured reduction of seizure frequency by half, proportion of people with no seizures (seizure freedom), side effects, and improvement in quality of life. We found six trials representing 125 participants for the present review. They reported two different comparisons: melatonin versus placebo and melatonin 5 mg versus melatonin 10 mg. Included trials did not evaluate seizure frequency, seizure freedom, and adverse events in a methodical way. Only one study reported seizure frequency and none of the participants had a change in frequency occurring during the trial compared to before the trial. Only one trial evaluated the effect of melatonin on quality of life and found no improvement with add-on melatonin compared with add-on placebo. The included trials were of poor methodological quality and it was not possible to draw any definitive conclusions about the role of melatonin in reducing seizure frequency or improving the quality of life in people with epilepsy. The evidence was current to January 2016.
+The review authors set out to determine whether surgery within 24 to 72 hours of onset of symptoms decreases the risk of death or dependence; and whether one surgical technique is better than another. Endoscopic or stereotactic surgery inserts a fine catheter rather than having to open up the skull (craniotomy) to get to the blood clot. This updated review included 10 studies in which a total of 2059 participants received medical treatment, but 50% also had surgery within 72 hours of onset of the event. Surgery was associated with significant benefit and improved the proportion of participants alive and independent. However, the benefit was not consistent in all the studies, which suggests that this result may not be very reliable. Overall, surgery appeared promising, though further trials are underway to identify the type of patients most likely to benefit from surgery.
+The review authors included five randomised and one controlled clinical trial involving a total of nearly 450 patients. In general the quality of the studies was good. Amputation after 12 months was required less often when SCS was added to standard care. Significant pain relief occurred with and without SCS but patients in the SCS group required fewer pain killers. Overall there was no difference on ulcer healing rates between the two treatment groups. Complications of SCS treatment consisted of problems with initially implanting the electrodes, in 8% of patients, and the need for repeat surgery because of electrode or lead failures in 12% of patients; infections occurred less frequently (3%). The average overall costs at two years were calculated in one study and found to be EUR 36,500 in the SCS group and EUR 28,600 in the conservative treatment alone group.
+We found eight trials on 870 people comparing hospital at home with  hospital care. The results from these trials show that fewer people are readmitted to hospital if they received their care at home. There was no significant difference in quality of life, although patients and carers said they preferred treatment at home. There was no significant difference in the number of deaths. These results are only applicable to a subgroup of patients who could be treated at home, but for a majority of the patients with acute COPD exacerbations, "hospital at home" schemes are probably not an suitable option.
+We searched medical databases and found three studies involving 1694 participants (CAMMS223, CARE-MS I and CARE-MS II). CAMMS223 involved people with previously untreated, early RRMS. Participants received either subcutaneous (under the skin) interferon beta 1a (at a dose of 44 μg) three times per week or annual intravenous (into a vein) courses of alemtuzumab (at a dose of either 12 mg per day or 24 mg per day) for 36 months. CARE-MS I enrolled adults aged 18 to 50 years with previously untreated RRMS. Participants received annual intravenous courses of alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 μg three times per week for 24 months. CARE-MS II enrolled adults aged 18 to 55 years with RRMS and at least one relapse while on interferon beta or glatiramer (another medicine that alters the immune response) treatment. Participants received subcutaneous interferon beta 1a 44 μg three times per week, annual intravenous courses of alemtuzumab 12 mg per day or annual intravenous courses of alemtuzumab 24 mg per day for 24 months. The evidence is current to 1 February 2017. The review of trials found that, compared with subcutaneous interferon beta 1a three times per week, annual intravenous cycles of alemtuzumab probably reduces the proportion of participants who experience relapse, may reduce the proportion of participants who experience disability worsening and development of new T2 lesions on MRI. In one study, alemtuzumab 24 mg leads to slightly better EDSS scores when compared with interferon beta 1a. The rates of adverse events were similarly high for both treatments. The most frequently reported adverse events for both treatments were infusion-associated reactions, infections and autoimmune events. The use of alemtuzumab requires careful monitoring so that potentially serious adverse events can be treated early and effectively. The quality of the body of evidence obtained for each outcome is mainly low except for the number of participants experiencing at least one relapse for which the quality of evidence was moderate.
+This review assessed seven studies of parecoxib, an injectable COX-2 inhibitor, for acute postoperative pain relief. Single doses of 20 mg or 40 mg provided effective pain relief in 50 to 60% of treated individuals, compared with 15% treated with placebo. Duration of pain relief was longer with the higher dose (10.6 hours for 40 mg versus 6.9 hours for 20 mg), and significantly fewer individuals on the higher dose required rescue medication over 24 hours (66% versus 81%). Adverse events were generally mild to moderate in severity and were reported by just over half of treated individuals in both parecoxib and placebo groups.
+Two studies met our inclusion criteria. The first study, based in the US, aimed to investigate how to increase the frequency people undertake skin self-examinations. All 1356 participants were asked to complete follow-up telephone interviews at 2, 6, and 12 months after randomisation. The average age of participants was 53.2 years; 41.7% were men. The second study included 18 communities in Australia (63,035 adults) that were assigned to either have a three-year community-based melanoma screening programme or not. The study did not report information on the mean age or proportion of men and women in the whole study population, but the average age of those attending the skin screening clinics was 46.5 years and 51.5% were men. The study lasted three years; outcomes were measured at the screening clinics during this time. There was no further follow-up. The purpose of the study was to investigate whether it was possible to conduct a larger trial, which was stopped by lack of funding. The first study was funded by the National Cancer Institute (US); the second, by Queensland Cancer Fund and Queensland Health (Australia). There was no information from either study on the effects of screening on total deaths, overdiagnosis from screening, or participant quality of life. The following outcomes were also not reported: deaths from skin cancer and false-positive/-negative rates (i.e. diagnosing a skin lesion as a melanoma when it is not present/not recognising a melanoma when it is present). Thus, we do not know whether screening for malignant melanoma results in any benefit, or whether such a possible benefit would be outweighed by harms of screening. General adult population screening for malignant melanoma is not supported or refuted by evidence from well-designed trials up to May 2018 and therefore does not fulfil accepted criteria for implementing screening programmes. We could not assess the reliability of the evidence for our primary outcomes as they were not assessed.
+The evidence is current to November 2017. We included 28 randomized studies with 4507 participants in the review. We are awaiting sufficient information for the classification of four studies. All studies included elderly people undergoing non-cardiac surgery and compared use of propofol-based TIVA versus inhalational agents during maintenance of general anaesthesia. We found little or no difference in postoperative delirium according to the type of anaesthetic maintenance agents from five studies (321 participants). We found that fewer people experienced postoperative cognitive dysfunction when TIVA with propofol was used in seven studies (869 participants). We excluded one study from analysis of this outcome because study authors had used methods to anaesthetize people which were not standard. We found little or no difference in the number of deaths from three studies (271 participants). We did not combine data for low blood pressure during the operation or length of stay in the PACU because we noted differences in studies, which may be explained by differences in patient management (for low blood pressure), and differences in how length of stay in the PACU is defined in each study . We found little or no difference in length of hospital stay from four studies (175 participants). Many studies did not report randomization methods adequately and all studies were at high risk of bias from anaesthetists, who needed to be aware of which anaesthetic agent they used. Outcome assessors in some studies were aware of which study group participants were in. We noted a large loss of participants in three studies, and some studies had differences between groups in the types of drugs used for pain, the types of monitors used to assess how deeply-unconscious the patients were, and participant characteristics at the start of the studies; these factors may have influenced the results. Few studies had reported clinical trials registration. We found few studies for two outcomes (mortality and length of hospital stay), which made the results less precise. We judged evidence for postoperative delirium, number of deaths, length of stay in the PACU, and length of hospital stay to be very low certainty, and evidence for postoperative cognitive dysfunction, and low blood pressure during the operation to be low certainty. TIVA with propofol may reduce postoperative cognitive dysfunction. We are uncertain whether the choice of anaesthetic agents (TIVA with propofol, or inhalational agents) affects postoperative delirium, mortality and length of hospital stay. We found 11 ongoing studies in database and clinical trials register searches. Inclusion of these studies in future review updates will provide more certainty for the review outcomes.
+We found 14 trials; most were small (involving 1071 infants in total) and were flawed methodologically. Multi-nutrient fortification of breast milk for preterm infants is associated with small increases in rates of weight gain, length gain and head growth during neonatal unit admission. Only very limited data are available for growth and developmental outcomes assessed beyond infancy, and these show no effects of fortification. Trials report no consistent evidence of other potential benefits or harms of fortification, including effects on risk of feeding or bowel problems. Although available trial data show that multi-nutrient fortification increases growth rates of preterm infants during their initial hospital admission, they do not provide consistent evidence on effects on longer-term growth or development. Additional trials are needed to resolve this issue.
+After searching for all relevant studies to August 2015, we found seven small randomized controlled trials (considered the highest quality study design) involving 691 participants aged 17 to 78 years. The results indicated that periodontal therapy as an added treatment had some benefits on eradication of gastricH. pylori for short-term and long-term follow-up. The eradication (the reduction of the prevalence of H. pylori in stomach to normal range) and non-recurrence (the proportion of participants that remained free of gastric H. pylori after successful eradication therapy) rates increased in people who received periodontal therapy plus eradication treatment, when compared with those who received eradication treatment alone. Because there were not very many participants or trials included in our analyses, we cannot draw a firm conclusion about the use of periodontal therapy for all patients with gastric H. pylori infection in clinical practice. Based on the results in this review, large-scale randomized controlled trials comparing periodontal therapy plus eradication treatment with eradication treatment alone would be useful to generate stronger evidence on the use of periodontal therapy as an additional treatment for patients with gastric diseases caused by H. pylori.
+Thirteen randomised controlled trials involving 648 participants were included in this review. Eleven of these were conducted in Italy. However, there is not enough reliable evidence from the research that has been done to date to be confident of a difference between GHB and placebo, or to determine reliably if GHB is more or less effective than other drugs for the treatment of alcohol withdrawl or the prevention of relapses. Six trials with a total of 286 participants evaluated the effectiveness of GHB in reducing withdrawal syndrome. These compared the drug with a variety of other interventions, making it impossible to use them all in a single analysis. One study suggests that GHB might reduce withdrawal symptoms more than a placebo, but this is based on a very small number of patients. No strong differences were observed between GHB and benzodiazepines or Clomethiazole. In the other comparisons, the differences were not statistically significant. Seven trials involving 362 participants tested the use of GHB to treat alcohol dependence or prevent relapses if a person was already detoxified (mid-term outcomes). These included several different comparisons, so each analysis was able to include only one or two trials; and the trials were generally small (range 17 to 98 participants). GHB did appear to be better than Naltrexone and Disulfiram in maintaining abstinence and preventing craving, based on two trials and one trial respectively for these comparisons. The most consistently reported side effect of GHB was dizziness and vertigo, with this being more common at higher doses. The findings of this review should be considered alongside concerns that have been raised about GHB regarding the risk of developing addiction, and the misuse or abuse of the drug, suggesting to use GHB only under strict medical surveillance.
+We systematically investigated studies that have compared massage therapy with other forms of therapy or no therapy. We found four randomised controled trials that used massage therapy with children, adolescents or adults with HIV or late-stage AIDS. This review of the literature supports that massage therapy can benefit people with HIV/AIDS by improving quality of life, particularly if they receive the therapy in conjunction with other techniques, such as meditation and relaxation training, and provide more benefit than any one of these techniques individually. Furthermore, it may be that massage therapy can improve their body's ability to fight the disease; however, this is not yet convincingly proven. We recommend further studies be undertaken to investigate this question and recommend that in the meantime, people with HIV/AIDS use massage therapy to improve quality of life, provided they have clear goals and monitor their response to the therapy.
+This review identified thirty-four methodological studies in which collections of systematic reviews were examined.  We identified four methodological approaches to assess the effects on health equity, a descriptive assessment in the reviews, a descriptive assessment of the trials included in the reviews, analytic approaches, and applicability assessment. However, the most appropriate way to address any of these approaches is unclear. There is a need for methodological guidance on how to assess effects on health equity in systematic reviews.  Analysis of particular groups of populations need to be justified and reported in sufficient detail to allow their credibility to be assessed. There is a need for improved transparency of judgments about applicability and relevance to disadvantaged populations.
+We identified five randomised controlled studies that were relevant to the review question that directly compared different thyroidectomy surgical techniques. A total of 886 participants were included in the studies and follow-up was between six months and six years. All five studies were conducted in university hospitals or tertiary referral centres for thyroid disease. The countries involved were Germany, Sweden, Poland and Taiwan. No study was performed in an outpatient setting. Total thyroidectomy is likely to give better control of hyperthyroidism compared to subtotal thyroidectomy (8 or 9 people out of 1000 will experience recurrence of hyperthyroidism after total thyroidectomy compared with 55 to 67 people out of 1000 after subtotal thyroidectomy). There is some evidence to suggest permanently low blood calcium (hypoparathyroidism) is more likely in total thyroidectomy compared to subtotal thyroidectomy (59 people out of 1000 after total thyroidectomy compared with 14 people out of 1000 after subtotal thyroidectomy will experience this side effect). Eye symptoms as well as permanent damage to the recurrent laryngeal nerve appear to be unrelated to the choice of surgical technique. Deaths were rarely reported in the included studies. No study evaluated health-related quality of life or socioeconomic effects (such as absence from work). The studies in this review suffer from a lack of high quality evidence. Several risk of bias problems were visible such as objective measurements of outcomes without knowing the allocation of participants to the intervention groups (total or subtotal thyroidectomy) and difficulties in finding out if all planned outcomes in studies were really reported in the publications of these studies. Also, rates of outcomes (event rates) were rather low, making our estimation of the differences between the surgical techniques imprecise. Finally, all thyroidectomies were performed by experienced surgeons and it is unknown whether the described results will be the same in other settings. This plain language summary is current as of 22 June 2015.
+We identified 23 randomised trials (maximum duration of eight months) including 1075 people in which omega-3 PUFA was compared to a vegetable oil or placebo. None of the trials looked at cardiovascular endpoints in cardiovascular disease or death as an outcome measure.  The review shows that although some types of fat in the blood are reduced through omega-3 supplementation, others including LDL cholesterol (which may promote heart disease) were increased. Control of blood sugar levels was not affected by the treatment. There were no other adverse effects of the interventions noted. Clinical outcome trials of sufficient duration are required to establish conclusively the role of omega-3 PUFA in type 2 diabetes but our results do not suggest a major harmful effect on the balance of blood fats and confirm that it has no adverse affect on blood sugar control.
+This review looked at six trials, with a combined total of 885 patients, which compared different methods of making these grafts. Results from two trials which looked at the effect of inserting a cuff of vein at the lower end of the synthetic graft before attaching it to the artery below the knee are conflicting. With one study showing that the bypass graft remains functional for a longer period of time and in the other study no benefit was seen. If a synthetic graft is made in a fashion imitating the shape of a vein cuff, then the same benefit can be achieved. The results also show that when short lengths of vein are joined together to form a sufficiently long graft, the bypass works for longer, although this does not result in fewer amputations. Finally, there is no added benefit for graft patency or amputation rate if a connection is made between the artery and the vein (fistula) when constructing a vein cuff with the synthetic graft but the operation takes longer.
+This review examines the evidence from ten randomised controlled trials involving 544 patients which compared heliox to oxygen or air, when used in conjunction with the other standard acute treatments. The reviewers conclude that the evidence does not support routine use of heliox in patients with acute asthma.
+Searches for randomised trials were run in 2010 and 2012, review authors found 22 relevant trials that randomised a total of 2041 people with schizophrenia. The trials compared the effects of taking a variety of antioxidants (allopurinol, Ginkgo biloba, N-acetyl cysteine (NAC), selegiline, vitamins C and E) compared with placebo. Most results showed no real differences between the antioxidants and placebo although there was evidence Ginkgo biloba had a positive effect on psychotic symptoms in the short term. The quality of this evidence was moderate. However, overall, the trials suffered from a lack of real-world outcomes, such as clinical response, rates of relapse, quality of life, functioning, safety and satisfaction or acceptability of treatment. Adverse effects were also poorly reported with some studies not providing any data for adverse effects. Ginkgo biloba and NAC emerged from the trials as the most promising, so should have priority in the design of future trials that are larger, longer and better reported than the 22 studies available at the present time. Ben Gray, Senior Peer Researcher, McPin Foundation: http://mcpin.org/
+This review examined whether caffeine improves the pain-relieving effects of such medicines. We searched for studies up to August 2014 and included twenty studies (7238 participants) examining several pain conditions, including headache, post-dental pain, postoperative pain following childbirth, and menstrual period pain. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement. Many of those in post-dental and postoperative pain were small, and small studies can overestimate benefits. A dose of caffeine equivalent to a mug of coffee added to a standard dose of common analgesics such as paracetamol or ibuprofen provided better pain relief. Analgesic plus caffeine increased the number of people who had a good level of pain relief by 5% to 10% compared with analgesic alone (high quality evidence). No serious adverse events were reported that were related to either the analgesic or caffeine in these studies (low quality evidence). It is unlikely that adding caffeine to an analgesic will be harmful if the recommended dose is not exceeded.
+We searched the medical literature and registers of ongoing trials for randomised controlled trials of at least 12 weeks' duration comparing insulin secretagogues with another glucose-lowering drug, placebo or no intervention. Randomised controlled trials are clinical studies in which people are randomly allocated to one of two or more groups so that the effects of different interventions can be compared directly. Participants included in the studies had to have glucose levels higher than considered normal, but below the glucose levels that are used to diagnose type 2 diabetes mellitus. We combined the findings of several studies to answer our review question. We found six randomised controlled trials. A total of 10,018 participants were included. The duration of the interventions varied from six months to five years. This evidence is up to date as of April 2016. Few participants died following treatment with sulphonylureas. Sulphonylureas (most of the evidence was available for glimepiride) did not reduce the risk of developing type 2 diabetes mellitus compared with placebo. No study with sulphonylureas reported on serious side effects, non-fatal heart attacks, non-fatal stroke, heart failure, health-related quality of life or socioeconomic effects. Only one study reported data on a meglitinide analogue (nateglinide). This large study contributed 95% of all participants of our review. We could not establish firm evidence on the outcomes death from any cause, risk of developing type 2 diabetes mellitus or serious side effects. This study did not report on health-related quality of life or socioeconomic effects. Future studies should investigate patient-important outcomes and, especially, the side effects of the medications, because we do not know for sure whether 'prediabetes' is just a condition arbitrarily defined by a laboratory measurement or is in fact a real risk factor for type 2 diabetes mellitus, which might be treatable. All included trials had deficiencies in the way they were conducted or how key items were reported. For the individual comparisons the number of participants was small, resulting in a high risk of random errors (play of chance).
+We found only one relevant study. It included 1956 adult participants, of whom 74% were men, who tested positive for HIV-type 1 and were eligible to start highly active antiretroviral therapy including a medication called abacavir. (Antiretrovirals are a drug class used for treating patients with HIV infection.) The age of study participants ranged from 18 to 77 years; the average age was 42 years. The participants were from 19 countries around the world in 265 healthcare centres (e.g. hospitals, clinics). This study investigated whether the following can reduce the rate of serious skin reactions to abacavir: genetic testing for the genetic marker HLA-B*57:01 before prescribing abacavir (i.e. prospective testing) versus no prospective genetic testing for HLA-B*57:01. HLA-B*57:01 is known to be key in developing severe skin reactions to the HIV antiretroviral drug, abacavir. Participants who tested positive for the genotype were not given abacavir; instead, they were given a different antiretroviral therapy. The study lasted six months and each participant was observed for six weeks. GlaxoSmithKline, the company that manufactures abacavir, funded the study. Control participants had HLA-B*5701 pharmacogenetic testing after they had received abacavir as standard of care. Our one included study did not report data for all participants, and clinical assessment of hypersensitivity (HSS) was done at the time of study entry, at baseline (day one) and at weeks one, two and six, without using predefined criteria. These can be important sources of bias and the quality of evidence was therefore judged to be moderate. Available data showed that prospective HLA-B*57:01 screening probably reduces the incidence of hypersensitivity reaction to abacavir (including, but not limited to, our secondary outcomes of hypersensitivity (HSS) syndrome and Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (i.e. severe and blistering skin reactions caused by medications)). Based on these results, we would expect that out of 1000 people who did not have prospective pharmacogenetic screening (i.e. screening to assess how someone might respond to a particular drug), 78 would experience a hypersensitivity reaction including SJS/TEN (clinical assessment), compared with between 22 and 52 people who did have prospective pharmacogenetic screening to test for HLA-B*57:01. Furthermore, we would expect that out of 1000 people who did not have prospective pharmacogenetic screening (standard care), 27 would experience a hypersensitivity reaction including SJS/TEN (immunologically confirmed), compared with zero participants who had prospective pharmacogenetic screening to test for HLA-B*57:01. A patch test on the skin provided immunological confirmation 6 to 10 weeks after clinical diagnosis. The study did not measure the other outcomes of this review. The evidence is current to July 2018. The included study was rated as being of moderate quality. Some patients were withdrawn from the study and not included in the analyses, and the investigator that diagnosed HSS reactions did not use a predefined clinical criteria of hypersensitivity. These issues caused us to downgrade the certainty of the evidence.
+Trials were made of early detection methods such as the testing of sputum, x-ray and computed tomography (CT) scanning of the chest to see whether they made a difference to the number of people who were treated by surgery and the number of people who died as a result of the disease. This review examined the evidence from nine trials (with a total of 453,965 participants) and found that early screening with chest X-ray or sputum testing does not reduce the number of people who die from lung cancer. Screening with low-dose chest CT was found in one large trial to reduce the number of people who die from lung cancer but this trial only included very high-risk smokers and ex-smokers. CT screening however is associated with a high number of false positive results and there are also some people who have lung cancer detected and treated but in whom this cancer may not have progressed to cause death in their lifetime, even in the absence of treatment (referred to as overdiagnosis). More research is needed about the relative harms and benefits of CT screening in individuals at lower risk for lung cancer.
+We searched a wide variety of scientific databases for randomised controlled trials (studies that allocate participants to one of two or more treatment groups in a random manner) in adults (over 18 years of age) who had a heart attack, had angina (chest pain), underwent coronary artery bypass grafting (a surgical procedure that diverts blood around narrowed or clogged sections of the major arteries to improve blood flow and oxygen supply to the heart muscle) or percutaneous coronary intervention (a procedure that opens up blocked coronary arteries), or with heart failure who were eligible for cardiac rehabilitation. Reviewers found 26 trials (5299 participants) that were suitable for inclusion (16 trials of interventions to improve enrolment, eight trials of interventions to improve adherence, and seven trials of interventions to improve programme completion). These studies evaluated a variety of techniques to improve utilisation such as providing peer support, starting cardiac rehabilitation early after hospitalisation, providing patient education, offering cardiac rehabilitation outside a hospital setting, and offering shorter programmes or women-only programmes. Strategies to increase enrolment were effective, particularly those that targeted healthcare providers, training nurses, or allied healthcare providers to intervene face-to-face. Interventions to increase adherence to programmes and to increase completion were effective, but it remains unclear which specific strategies were implemented. We found no studies providing information about potential harms and two studies reporting costs of these strategies to increase use of cardiac rehabilitation. Some studies provided interventions to increase rehabilitation utilisation in women and older patients. Evidence was insufficient for quantitative assessment of whether women-tailored programmes were associated with increased utilisation, but motivating women appears key. For older participants, qualitative analysis suggested that peer support or postdischarge visits may improve enrolment, and group sessions promoting self-regulation skills may increase completion. Most of the included studies were of good quality (i.e. low risk of arriving at wrong conclusions because of favouritism by researchers). The quality of the evidence was low for enrolment and adherence and was moderate for completion. Publication bias for enrolment was not evident.
+Altogether 12.864 people took part in 25 studies investigating the new compounds sitagliptin and vildagliptin. Most studies lasted 24 weeks, the longest trials evaluated 52 weeks of treatment. So far, no study reported on patient-oriented parameters like mortality, diabetic complications, costs of treatment and health-related quality of life. When compared to placebo treatment sitagliptin and vildagliptin improved metabolic control. Comparison with other already established blood-glucose lowering drugs did not reveal advantages of DPP-4 treatment. Weight gain was not observed after sitagliptin and vildagliptin therapy. Overall, sitagliptin and vildagliptin were well tolerated, no severe hypoglycaemia was reported in patients taking sitagliptin or vildagliptin. However, all-cause infections increased significantly after sitagliptin treatment but did not reach statistical significance following vildagliptin therapy. Unfortunately, all published randomised controlled trials of at least 12 weeks treatment with sitagliptin and vildagliptin only reported routine laboratory safety measurements. Since the new DPP-4 inhibitors may influence immune function additional long-term data on the safety of these drugs are necessary. Also, cardiovascular outcomes like heart attacks and strokes should not be increased with any antidiabetic therapy but data so far are lacking. Until new information arrives, DPP-4 inhibitors should only be used under controlled conditions and in individual patients.
+We included 10 randomised clinical trials (clinical studies where people are randomly put into one of two or more treatment groups) with 898 participants. All the trials were at high risk of bias. The trials covered oral capsules, intravenous (into a vein) infusion, intramuscular (into a muscle) injection, and acupoint (a specifically chosen site of acupuncture) injection of Radix Sophorae flavescentis with treatment duration from 1 month to 12 months. Radix Sophorae flavescentis was compared with lamivudine, adefovir, interferon, tiopronin, thymosin, and other Chinese herbs. Two trials included children up to 14 years old. Participants in one trial had cirrhosis (late stage of scarring of the liver) in chronic hepatitis B. Two of the 10 trials were not funded, and one received governmental funding. The remaining seven trials provided no information on funding. Undisclosed funding may have influence on trial results and lead to poor design of the trial. None of the trials reported health-related quality of life (a measure of a person's satisfaction with their life and health), or followed people who have died from any reason or died from hepatitis B, or who were at risk of dying because of hepatitis B. Side effects considered 'not to be serious' was an outcome in two trials. We could not say if Radix Sophorae flavescentis versus other medicines or herbs was better or worse regarding the occurrence of side effects considered 'not to be serious'. We were uncertain whether Radix Sophorae flavescentis had a positive, neutral, or negative effect on the proportion of participants with detectable HBV-DNA (the genetic blueprint of the virus). Radix Sophorae flavescentis may have reduced the proportion of participants with detectable hepatitis B virus e-antigen (HBeAg; produced by the immune system). However, caution is needed with these findings as the trials providing data on them were small, at high risk of bias, and these outcomes have not yet been proven relevant to people with HBV infection. We identified 109 trials that not be included because of lack of information required for the conduct of this review. Accordingly, more information from properly designed randomised clinical trials is needed before one can determine the benefits or harms of Radix Sophorae flavescentis for people with chronic hepatitis B. Certainty of evidence means 'the extent of one's confidence that review results are correct in supporting or rejecting a finding.' The certainty of the evidence on the use of Radix Sophorae flavescentis in people with chronic HBV in terms of its beneficial or harmful effects on death, health-related quality of life, risk of dying due to HBV infection, and serious side effects cannot be determined as none of the trials reported patient-relevant outcomes. Our certainty in the evidence that Radix Sophorae flavescentis, when compared with other medicines or herbs, would decrease or increase side effects considered 'not to be serious' and number of people with detectable HBV-DNA is very low. Our certainty in the evidence that Radix Sophorae flavescentis decreases the number of people with detectable HBeAg is also very low. These assessments of certainty of evidence are due to the poor design and reporting of the included trials.
+The purpose of this systematic review was to examine the effectiveness and safety of helminth therapy for inducing remission in people with IBD. This review identified two randomised controlled trials including a total of 90 participants. One study compared twice weekly treatment with helminths (an 0.8 mL solution containing 2500 live eggs of the helminth Trichuris suis) for 12 weeks to a matching placebo (an 0.8 ml identical looking solution with no Trichuris suis eggs) in 54 patients with active ulcerative colitis. Few remissions occurred during the trial and helminth treatment had no detectable effect on these remissions. Ten per cent (3/30) of patients in the helminth group achieved remission compared to four per cent (1/24) of placebo patients. A higher proportion of patients in the helminth group (43% or 13/30) improved clinically compared to the placebo group (17% or 4/24). However, this difference could be a chance effect. We could not determine whether the proportion of patients who had a side effect was higher in either group. No observed side effects were thought to be related to treatment were reported in this study. The other study compared one treatment with various doses of helminths (a solution of 500, 2500 or 7500 Trichuris suis eggs) to a matching placebo in 36 patients with Crohn's disease. This study was designed to assess side effects and did not measure clinical remission or improvement. There amount of information available on side-effects at two weeks was limited and the results were uncertain due to the small number of participants in the study. The only side effect that was judged to be possibly related to the study treatment was dysgeusia (a distortion of the sense of taste). This was reported in one patient in the helminth group and in one patient in the placebo group. Currently, there is insufficient evidence to allow any firm conclusions regarding the effectiveness and safety of helminths used to treat patients with IBD. The only information available relating to clinical improvement in patients with active ulcerative colitis comes from one small study. We do not know how safe helminths are when used in patients with ulcerative colitis and Crohn's disease. Further randomised controlled trials are required to assess the efficacy and safety of helminth therapy in IBD.
+We identified seven studies, enrolling 767 patients that compared haemodialysis catheter insertion using the traditional 'blind' landmark method and insertion using ultrasound imaging. The use of ultrasound imaging was found to be associated with significantly less risk of arterial puncture and haematomas and less time to insert the catheter as well as a higher success rate for inserting the catheter on the first attempt.
+The types of studies that could be included in this review are randomised controlled trials, cluster randomised controlled trials, controlled before-after studies, and interrupted times series studies. We found 21 studies looking at the effects of 11 different types of cycling infrastructure. No studies reported self-reported injuries or medically attended injuries. Fourteen studies reported police-reported ‘cycle crashes’ or ‘accidents’ or ‘injury crashes’ and the other studies reported outcomes such as number of “cycle accidents” or “crashes involving cyclists”. Nine studies reported collisions by severity; seven studies reported on age of casualty; and two studies reported on sex. One study reported on the level of social deprivation. Cycle flow was collected in 14 studies. Generally we found a lack of evidence that the types of cycling infrastructure we looked at affects injuries or collisions in cyclists. Cycle routes and networks do not seem to reduce the risk of collision. Speed limits of 20 mph, changing parts of the road network to some designs of roundabouts and changing busy parts of a cycle route may reduce the risk of collision. In terms of severity of injury, sex, age and level of social deprivation of the area, there is a lack of evidence to draw any conclusions concerning the effect of cycling infrastructure on cycling collisions. We carried out a thorough search for relevant papers. The quality of the evidence was low with 20 of the included 21 studies using a controlled before-after study design. Few studies considered how factors such as weather and volume of traffic may affect collision rates. Few studies considered how changes in cycle rates seen as a result of installing infrastructure may affect changes in collision rates.
+This review found some evidence for relief with progesterone but trials differed in route of administration, dose, duration of treatment and selection of women taking part. Outcomes also differed. The studies had flaws in methods or in handling outcome data or both. Adverse effects which may or may not have been the result of the treatment were generally mild. Further research would be needed to test claims for the effectiveness of higher doses of progesterone. They are neither refuted nor borne out as yet. Using each woman's own symptoms to select participants and to judge treatment effects would be more accurate than checklists of largely irrelevant symptoms. Knowing how many women had fewer days with symptoms, fewer or milder symptoms, or the converse, would be more valuable than the calculations based on subjective data for groups of women.
+This review found that first-line chemotherapy (anticancer drugs) may prolong the survival of patients with advanced small cell lung cancer for some months when compared to supportive care, although the effect of this treatment on quality of life is unknown. The benefit of a new treatment (second-line chemotherapy) when the disease has progressed or relapsed was even smaller, and the potential survival gain of some weeks must be balanced against its possible secondary effects. Since the available studies were scarce and of variable quality, more clinical trials are needed to assess and better inform patients about the real effectiveness of chemotherapy in advanced small cell lung cancer.
+In this review, we identified 23 trials involving 3198 pregnant women. Many of the trials were in low-income countries and many treatment variations were studied. Oral iron reduced the incidence of anaemia but is known to sometimes cause constipation and nausea. Although the intramuscular and intravenous routes produced better levels of red cells and iron stores than the oral route, no clinical outcomes (such as pre-eclampsia, preterm births, postpartum haemorrhage) were assessed and there were insufficient data on adverse effects. Intravenous treatment can cause venous thrombosis (blockages in the veins) and intramuscular treatment causes important pain and discolouration at the injection site. It was unclear if women and babies were healthier when women were given iron for mild or moderate anaemia during pregnancy. There were no studies on using blood transfusions. Overall, there was insufficient evidence to say when or how anaemia in pregnancy needs to or should be treated.
+We searched for studies from the year in which the first paper about using ultrasound to diagnose trauma patients was published until 15 July 2017. We considered 2296 records and included 34 relevant studies that involved 8635 participants in this review. All 34 studies were published between 1992 and 2017, with the number of participants in each study ranging from 51 to 3181. Ten studies included only children, two studies only adults, and the remaining 22 studies included both children and adults. In many studies, important information about the selection of participants and choice of the diagnostic tests against which to compare POCS was not reported. We therefore rated the methodological quality of the available evidence mostly as unclear. Point-of-care sonography had a sensitivity (i.e. the ability to detect a person with the disease) of 74% and a specificity (i.e. the ability to exclude a person without the disease) of 96%. Sensitivity and specificity varied considerably across studies, which was due in part to variation in study, participant, and injury characteristics. In children, both the sensitivity and specificity of POCS were lower than in an adult or mixed population, meaning that POCS was less able to identify or rule out an injury. Based on our results, we would expect that amongst 1000 patients of a mixed-age population with suspected blunt trauma to the abdomen or chest, POCS would miss 73 patients with injuries, and would falsely suggest the presence of injuries in 29 patients who were unaffected. This result emphasises the need for additional imaging in trauma patients for whom POCS shows no injuries (i.e. a negative result), to check whether they are really injury-free.
+Four clinical trials with 355 children were identified which compared the effect of symptom-based versus to peak flow written action plans when all other co-interventions were similar. Children assigned to a symptom-based plan less frequently required an acute care visit for asthma compared to those who received a peak flow based plan. Most other outcomes were similar with the exception of more children intending to continue using the symptom-based compared to the peak-flow based written action plan.
+This review assessed both the pain-relieving effectiveness and the adverse effects of a single dose of aspirin in acute postoperative pain of moderate to severe intensity. We included 67 studies, with 3111 participants given aspirin in comparisons with 2632 given placebo. Most of the information was for a 600 mg or 650 mg dose. The results confirm that in patients with moderate to severe postoperative pain, about 40% of those treated with aspirin 600/650 mg will experience good levels of pain relief, compared with about 15% treated with placebo. This level of pain relief is comparable to that experienced with the same dose of paracetamol. In these single dose studies there was no significant difference between aspirin 600/650 mg and placebo for the number of participants experiencing adverse events, but at 900/1000 mg, twice as many did so, with dizziness, drowsiness, gastric irritation, nausea, and vomiting being the most common events reported.
+The evidence is current to January 2019. We included 20 randomized controlled studies involving 1406 participants. The studies looked at diverse approaches to HAI prevention. These approaches included strategies to acclimatize to high altitudes by mimicking quick ascents by reducing levels of oxygen in the air that participants are breathing, and herbal products or vitamin supplements available without a prescription. The participants ranged in age between 17 and 65 years. Only one study included people at high risk of developing HAI as they had a history of HAI. Four trials provided the intervention between one to three days before making the ascent (20% of the studies), and eight between four to 30 days before departure for the ascent (40% of the studies). The participants in all these studies reached a final altitude of between 3500 and 5500 metres above sea level. Most of the studies did not provide clear information on how they were funded (55% of studies). Thirty additional studies were classified as either ongoing (14 studies), or awaiting classification (16 studies), and they will be considered in future versions of this suite of three reviews as appropriate. The evidence for any benefit of the various strategies is inconclusive, and even contradictory among the included studies. In three studies comparing normal levels of oxygen with low oxygen levels as a way of acclimatization before leaving for high altitudes, we found no differences in the risk of developing acute mountain sickness (3 trials, 140 participants; low-quality evidence). Adverse events were not reported, nor were high altitude cerebral oedema (HACE) or pulmonary oedema (HAPE). Ginkgo biloba was compared with taking an inactive placebo in seven studies (523 participants) looking at acute mountain sickness. There was no difference between ginkgo biloba and placebo in terms of the risk of developing HACE (3 studies, 371 participants), or in the risk of developing tingling or pricking, often described as 'pins and needles', as a side effect of treatment (2 studies, 352 participants). No HAPE events were reported (3 studies, 371 participants). Ginkgo biloba was compared with acetazolamide, which is a drug used to prevent acute mountain sickness, in four studies (397 participants). The findings differed between the studies, and no conclusions could be drawn. Acetazolamide increased the risk of developing pins and needles in two studies (354 participants). No HAPE or HACE events were reported. Overall, the limited information on the safety of the various interventions means that their safety remains unclear. The quality of the evidence was low to very low. We could not obtain the full text reports of some of the studies we had identified, which limited the number of studies included in the review. Many of the studies had small numbers of participants; and for some outcomes few events occurred so that any findings were uncertain. Additional research is needed to clarify the effectiveness and safety of the various strategies to reduce HAI.
+The aim of this review was to evaluate the effects of prostanoids in patients with IC. We identified 18 randomised studies with a total of 2773 participants, of which four studies compared the effects of PGE1 versus placebo. Overall, there was insufficient high quality evidence to suggest that PGE1 improves walking distances in people with IC. There was also a lack of evidence to determine if PGE1 was more effective than laevadosin, naftidrofuryl or L-arginine. Evidence on the efficacy of prostacyclin was inconclusive. Results suggest that, compared with PGE1, prostacyclin may be associated with an increased occurrence of side effects including headache, diarrhoea and facial flushing.
+Simple application of a single daily insulin injection in addition to oral hypoglycaemic agents may facilitate the initiation of insulin therapy in type 2 diabetes mellitus.This review examined 20 trials including 1,811 participants which compared insulin monotherapy with insulin in combination with oral hypoglycaemic agents (OHA) in insulin-requiring patients with type 2 diabetes. The results suggest that a bedtime NPH insulin-oral hypoglycaemic agent combination therapy regimen provides comparable glycaemic control to insulin monotherapy. Due to lack of studies it remains unclear whether insulin-OHA combination regimens with metformin alone are superior to those with metformin plus a sulphonylurea. In most cases no significant differences in hypoglycaemic events were observed between insulin mono- and OHA combination therapy. No study assessed diabetes-related morbidity or mortality.
+The author identified two small randomised controlled studies (with a total of 119 participants); one in France and one in Germany. One trial compared Gingko biloba to placebo and the other compared two different doses of the extract. Although both trials reported some positive effects of Ginkgo biloba on vision, the trials were small and of short duration. Adverse effects and quality of life were not assessed. The overall conclusion of this review is that current research has not answered the question as to whether Ginkgo biloba is of benefit to people with AMD. Future trials need to include a larger number of participants and be conducted over a longer time.
+We included 46 randomized studies, 40 on vasovagal syncope and six on carotid sinus syncope. No studies on situational syncope matched the criteria for inclusion in our review. Studies in general were small with a median size of 42 patients. A wide range of control treatments were used with 22 studies using placebo control treatment. Blinding of patients and treating physicians was applied in eight studies. The type of outcomes reported by studies varied considerably with only 16 studies reporting on non-provoked recurrences during follow-up. As a consequence of all these differences, results varied considerably between studies and between types of outcomes. In some studies significant results were reported for one type of outcome, but not for other outcomes. We conclude that there is insufficient evidence either to support or to refute the use of any of the pharmacological or pacemaker treatments for vasovagal syncope and carotid sinus syncope.
+We looked at the evidence up to February 2014 and included 11 studies involving 699 participants. Ten studies provided data for analysis.The studies involved adults (over 18 years of age) who were undergoing routine or emergency surgery. We did not include studies in which patients were kept cold deliberately during the operation, were having head surgery or skin grafts or were under a local anaesthetic. We looked at studies comparing different rewarming methods versus each other or versus normal care (hospital blankets). We can be quite certain that temperature goes back to normal (between 36°C and 37.5°C) more than an hour faster when active warming methods are used to warm hypothermic patients than when hospital blankets are used, and that this result is important for people involved in the care of patients with hypothermia after surgery. Not enough evidence was found to show whether active warming methods provide other benefits or harms to patients. Some evidence suggests that forced air warming (one type of active warming) is better at rewarming patients than circulating hot water devices and radiant heaters (other types of active warming), but we do not know whether forced air warming is the best active warming method overall, as evidence on all methods of active warming was not available. Quality of the evidenceMost of the evidence was moderate to low in quality. Methods used to assign patients to treatment groups were generally unclear or inadequate, and it was not possible to keep patients or people assessing patients unaware of the treatment given. This may have biased the results, but we are not sure what influence this could have had on the overall results.
+In total we found 63 trials recruiting 9168 stroke survivors within one year of their stroke. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. However, only three of these trials were at low risk of bias; the participants in these trials did not have to be depressed to enter the trial, and they were all recruited soon after the stroke. When we combined data from these three studies at low risk of bias, which recruited 3249 participants, SSRIs did not affect disability score or dependency. SSRIs reduced the risk of future depression but increased the risk of problems with the digestive system. There was no evidence of a substantial difference in seizures. When we combined data from all the studies, irrespective of risks of bias, there appeared to be a beneficial effect on recovery, but this was almost certainly because the studies at high risk of bias tended to give the positive results. The evidence is current until July 2018. We are confident that the results are reliable when we included just the studies at low risk of bias. When we included all studies regardless of risk of bias we found that SSRIs reduced disability. When they become available, we will include the results from two large ongoing trials in a future update.
+We included seven studies that enrolled a total of 651 participants (mean age 31.7 to 55.5 years) with chronic neck pain. Each study included between 30 and 218 participants. The participants received TENS or a control intervention (placebo or another type of treatment). The studies were very different in terms of the duration of the TENS sessions (from 20 to 60 minutes), number of sessions (from 1 to 12) and total duration of the treatment programmes (from 1 to 45 days). Because of the differences between each of the included studies, we decided that it would not be appropriate to combine their results. Out of the seven studies included, two reported that TENS was no better than inactive treatment (placebo) in reducing the participants' neck pain. None of the included studies assessed disability or adverse events. There was very low-certainty evidence about the effects of TENS for treating chronic neck pain.
+We searched scientific databases for randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) of people with uncontrolled or controlled hypertension with or without other risk factors (an aspect of a person's condition, lifestyle or environment that affects the probability of occurrence of a disease). The evidence is current to July 2014. We found no reliable difference between ACE inhibitors and ARBs for total deaths, deaths due to heart disease, or total heart disease and stroke. However, our conclusions alone cannot be taken to mean that ARBs would show similar benefit like ACE inhibitors if compared with placebo (a dummy treatment). ARBs do have a 1.8% lower chance of being stopped due to side effects over 4.1 years, meaning that for every 55 people treated with an ARB instead of an ACE inhibitor for 4.1 years, one person would be spared from a side effect leading to stopping the drug. This difference in side effects was mainly due to a higher rate of dry cough in people taking ACE inhibitors. In summary, while ARBs are slightly better tolerated than ACE inhibitors, there is a higher quality of data supporting the use of ACE inhibitors to prevent death, strokes, and heart disease that must be considered before choosing ARBs over ACE inhibitors.
+No evidence from trials that thyroid hormone therapy is effective in preventing problems such as respiratory distress syndrome in preterm babies. Thyroid hormones are needed for the normal growth and maturity of the central nervous system, as well as the heart and lungs. Children born without sufficient thyroid hormones can develop serious mental retardation. It is believed that low levels of thyroid hormones in the first few weeks of life (transient hypothyroxinemia) in preterm babies born before 34 weeks may cause this abnormal development. The review of trials found no evidence that using thyroid hormones in preterm babies is effective in reducing the risk of problems caused by insufficient thyroid hormones.
+We assessed the evidence from three clinical trials that compared topiramate with carbamazepine. We were able to combine data for 1151 people from two trials; we were not able to use the data from the remaining trial, which included 88 participants. Results Most (81%) of the people included in the two trials experienced focal seizures, so the results of this review apply mainly to people with this seizure type. Many of the remaining 19% of people experienced a seizure type which was difficult to classify as focal or generalised (unclassified seizures). Considering only people with focal seizures, the results showed that those taking carbamazepine were more likely to take their treatment for longer and to achieve a remission of 12 months duration earlier than those taking topiramate. No differences were found between the drugs in individuals with generalised onset or unclassified epilepsy. The most common side effects reported by the participants during the trials were fatigue, 'pins and needles' (tingling sensation), headache, gastrointestinal problems and anxiety or depression. These side effects were reported a similar number of times by people taking topiramate or carbamazepine. Certainty of the evidence For people with focal onset seizures, we judged the certainty of the evidence to be moderate to high. The design of the trials (whether the people and treating clinicians knew which drug they were taking) may have influenced how long a participant stayed on their treatment. For the small number of people with generalised onset or unclassified seizures, we judged the certainty of the evidence to be low to moderate. The evidence is current to May 2018. Conclusions Carbamazepine is currently recommended by experts for the treatment of individuals who are newly diagnosed with focal onset seizures and the results of this review do not provide any evidence to contradict this. More information is needed for people with generalised onset or unclassified seizures. All future trials comparing these drugs, or any other antiepileptic drugs, should be designed using high-quality methods, and the types of seizure of the people included in any trials should be classified very carefully to ensure that the results are of high quality.
+Our review included 13 randomised controlled trials involving 445 participants. These trials assessed: betamethasone (1 trial), thalidomide (5 trials), pentoxifylline (1 trial), clofazimine (3 trials), indomethacin (2 trials), and levamisole (1 trial). Generally, the quality of the studies was poor and many were too small to identify important clinical differences even if they existed. Three small trials showed benefit for thalidomide and clofazimine treatment in terms of fewer further reactions, more treatment successes, and less relapses of ENL. Adverse events were reported in most of the trials, but it was often not possible to compare the occurrence of any adverse events between the experimental group and control group. Most adverse events reported were not too serious, and only a few participants could not complete treatment due to serious adverse events or for other reasons. Whether the interventions improved the quality of life of participants, was not evaluated in any of the trials. Although we did not find clear benefits in these series of small, poorly-performed studies, this does not mean that these drugs do not work in the treatment of ENL, only that scientific evidence is insufficient. Future studies should be better designed and use clear definitions and outcomes, including long-term outcomes and quality of life measures.
+After searching for all relevant studies, 24 were identified for inclusion in the review with a total of 2882 people. The findings are summarised as follows. - Physical activity has a small benefit for managing fatigue in people with rheumatoid arthritis. - Psychosocial therapy has a small benefit for managing fatigue in people with rheumatoid arthritis. - No other interventions showed a difference in managing fatigue in people with rheumatoid arthritis. This may have happened by chance. The information available regarding side effects and complications of the interventions was not very informative although it is unlikely that any side effects would cause a serious problem. What is rheumatoid arthritis and what are non-pharmacological interventions? When you have rheumatoid arthritis, your immune system, which normally fights infection, attacks the lining of your joints. This makes your joints swollen, stiff and painful. The small joints of your hands and feet are usually affected first. There is no cure for rheumatoid arthritis at present, so the treatments aim to relieve pain and stiffness and improve your ability to move. Fatigue is also a problem for people with rheumatoid arthritis. Non-pharmacological interventions include any treatment that is not a registered drug, such as physical activity and psychosocial interventions (talking therapies). A talking therapy could include meeting with a counsellor, alone or in a group. It might involve writing about your thoughts and feelings in a journal and talking about it, problem-solving, setting goals and getting feedback about self-management. It might also include sessions on pain management and relaxation; and coping with depression. There are other non-pharmacological treatments that have been tested for their effect upon fatigue in people with rheumatoid arthritis. These include different dietary supplements and studies on the effects of giving people access to information about their own disease status. These treatments if supported by the overall body of evidence would allow the patient to have some personal control of their fatigue. What happens to people with rheumatoid arthritis who use non-pharmacological interventions? - At the end of the intervention, people receiving a control had a mean score of 63 on a scale of 0 to 100 with a lower score meaning less fatigue. - People who used physical activity rated their fatigue as 54 on a scale of 0 to 100 at the end of the intervention, that is 9 points lower than the people who received the control. - People who participated in a psychosocial intervention rated their fatigue as 57 on a scale of 0 to 100 at the end of the intervention, that is 6 points lower than the people who received the control.
+When compared with placebo, people taking aripiprazole had fewer relapses, smaller numbers of participants left study early, and needed less additional antipsychotic medications. Insomnia and headache were the most commonly reported side effects, but were not much difference to placebo. Side effects such as akathisia, nausea and weight gain occurred more in the aripripazole group as compared to placebo. There has been a worry with newer antipsychotic medications and their effect on conductance problems in the heart, impaired glucose levels and excessive production of prolactin (which can cause unpleasant breast pain and secretion). On the limited evidence available (due to participants leaving early and fewer studies) aripiprazole appears to have a similar effect to that of placebo. The overall finding on its efficacy in treating schizophrenia is unchanged from those found in the original review.
+We performed a rigorous search of the medical literature in October 2016 and found eight studies that compared treatment with BtA versus placebo. These studies included a total of 1010 participants, with on average a moderate disease impairment. The participants remained in the majority of studies for a short period of time - between 16 and 20 weeks after the treatment. The average age of people in the studies was 52.3 years, and they had had cervical dystonia for an average of 4.8 to 12.1 years before taking part in the trials. Most, 64%, of the people in the studies were women. Seven of the eight trials were funded by drug manufacturers with possible interests in the results of the studies. The results show that a single treatment session improved cervical dystonia symptoms, including pain, and participant's self-evaluations. However, the risk of having an unpleasant or undesirable event, particularly swallowing difficulties and tiredness, was also increased. Only three studies examined the impact of BtA on quality of life, suggesting some benefit from BtA. The certainty in the evidence for overall and pain improvement, the risk of undesired events, self-evaluation, the risk of swallowing difficulties, and the risk of participants not tolerating treatment, is moderate. Nevertheless, to be included in the studies, participants had to have a history of successful treatment with BtA. People with certain types of cervical dystonia, in particular the types that make the head turn mostly backward or forward, were not allowed to participate in the studies, and it is known that these types respond less to botulinum toxin treatment. Therefore, the conclusions from this review may not apply to all people with cervical dystonia. We can draw no conclusions regarding long-term effects of BtA for this condition.
+This summary of an updated Cochrane review presents what we know from research about the benefits and harms of manual therapy and exercise compared with placebo, no intervention or any other intervention in people with rotator cuff disease. After searching for all relevant studies published up to March 2015, we included 60 trials (3620 participants), however only 10 looked at manual therapy and exercise in combination. Among the included participants, 52% were women, average age was 51 years and average duration of the condition was 11 months. The average duration of manual therapy and exercise interventions was six weeks. Overall pain (higher scores mean more improvement in pain reduction) People who had manual therapy and exercise had improvements in pain that were little or no different to people who had placebo. Improvement in pain was 6.8 points more (ranging from 0.7 points less to 14.3 points more) at 22 weeks (7% absolute improvement). People who had manual therapy and exercise rated their change in pain score as 24.8 points on a scale of 0 to 100 points. People who had placebo rated their change in pain score as 17.3 points on a scale of 0 to 100 points. Function (higher scores mean more improvement in function) People who had manual therapy and exercise improved slightly more than people who had placebo. Improvement in function was 7.1 points more (ranging from 0.3 to 13.9 points more) at 22 weeks (7% absolute improvement). People who had manual therapy and exercise rated their change in function as 22.4 points on a scale of 0 to 100 points. People who had placebo rated their change in function as 15.6 points on a scale of 0 to 100 points. Treatment success 16 more people out of 100 rated their treatment as successful with manual therapy and exercise compared with placebo, 16% absolute improvement (ranging from 2% less to 34% more improvement). Fifty-seven out of 100 people reported treatment success with manual therapy and exercise. Forty-one out of 100 people reported treatment success with placebo. Side effects 23 more people out of 100 people had minor side effects such as temporary pain after treatment with manual therapy and exercise compared with placebo. Thirty-one out of 100 people reported side effects with manual therapy and exercise. Eight out of 100 people reported side effects with placebo. High quality evidence from one trial suggested that manual therapy and exercise improved function only slightly more than placebo at 22 weeks, was little or no different to placebo in terms of other patient-important outcomes (e.g. overall pain), and was associated with relatively more frequent but mild adverse events. Low quality evidence suggested that there may be little or no difference in overall pain and function when manual therapy and exercise is compared with glucocorticoid injection, there may be little or no difference in overall pain and function when manual therapy and exercise is compared with arthroscopic subacromial decompression, and people who receive acupuncture plus dietary counselling and Phlogenzym supplement may have less pain and better function than people receiving manual therapy and exercise. We are uncertain whether firstly, manual therapy and exercise improves function more than oral non-steroidal anti-inflammatory drugs (NSAID), and secondly, combining manual therapy and exercise with glucocorticoid injection provides additional improvement in function over glucocorticoid injection alone, because the quality of the evidence was very low.
+In this review, our search for randomised control trials that examined the effectiveness of pneumococcal vaccines for people with bronchiectasis revealed one randomised and one quasi-controlled trial. We conclude that, albeit the limitations of the review, adults and children (when age appropriate) with bronchiectasis should be vaccinated with the 23-valent polysaccharide pneumococcal vaccine as suggested in many national guidelines. Due to absence of data on how often the vaccine should be given, we recommend that national guidelines be followed until further evidence is available.
+32 studies involving 2626 women. The included studies were published up through March 2015. Not all studies considered all of these potential side effects. Combining the results of these studies suggests that physical exercise probably improves physical fitness and slightly lessens fatigue. These studies also suggest that physical exercise probably results in little or no improvement in cancer-specific quality of life and depression. Exercise may improve mental function and slightly improve cancer site-specific quality of life, although the quality of the evidence was low for both of these outcomes. It may result in little or no improvement in health-related quality of life, however the quality of evidence was low for this outcome. The quality of evidence may have been low because many of the studies did not have enough participants to observe small differences and because results may be biased due to people assessing the outcomes knowing which participants were in the control group. Importantly, physical exercise did not harm most women. Very few women experienced discomfort or pain in their arms or legs. It appears that exercise during cancer treatment can help lessen fatigue and improve physical fitness. It probably results in little or no improvement in cancer-specific quality of life and depression. It is unknown whether it helps for other side effects. At least nine current studies will help to answer the question if and how much exercise helps with the mentioned side effects and other side effects.
+We found a total of three studies involving 136 participants with an average age between 33 and 36 years with well-controlled asthma. They underwent water-based exercise from 40 to 60 minutes three to five times a week; the programme lasted 10 to 24 weeks in two studies, and one day only in one study. We considered data reported on quality of life, asthma general symptoms or asthma exacerbations, measure of lung function (FEV1, forced expiratory volume of the lung in the first second of air expired) and adverse events. The quality of evidence is very low because of issues with selection of participants, small number of participants, differences in exercise duration and intensity and differences in levels of asthma. Often surrogate endpoints were measured instead of patient-important outcomes. To sum up, more studies are needed to find out the effect and safety of water-based exercise for adults with asthma. The quality of evidence is very low because of issues with selection of participants, differences in exercise duration and intensity and differences in levels of asthma; surrogate endpoints were measured instead of patient-important outcomes. This plain language summary is current as of 13 May 2014.
+On 8 June 2016 and 4 August 2017 we ran electronic searches of the Cochrane Schizophrenia's specialised register of studies in order to find clinical studies that randomly allocated individuals at risk of developing psychosis to receive various treatments for preventing development of psychosis. We were able to include 20 studies with 2151 participants. These studies analysed a wide range of treatments. All the review findings are of, at very best, low quality. There is some suggestion from one small study that people at risk of psychosis may benefit from taking omega-3 fatty acids in terms of reduced transition to psychosis. Other studies found adding antipsychotic drugs to supportive-care packages did not seem to make much difference in terms of transition to full illness. When cognitive behavioural therapy (CBT) + supportive therapy was compared with supportive therapy alone around 8% of participants treated allocated to the combination of CBT and supportive therapy transitioned to psychosis during follow-up by 18 months, compared with double that percentage in people who just received supportive therapy. This could be important but these data are of very low quality. All other testing of CBT and other packages of care found no clear difference between treatments for transition to psychosis. There has been considerable effort and expense invested testing treatment approaches for prevention of the first episode of schizophrenia. Currently, there is some low-quality evidence suggesting that omega-3 fatty acids may be effective, but there is no high-quality evidence to suggest that any type of treatment is effective, and no firm conclusions can be made.
+A group of experts has developed a checklist and flow diagram called the CONSORT Statement. The checklist is designed to help authors in the reporting of randomised controlled trials (RCTs). This systematic review aims to determine whether the CONSORT Statement has made a difference to the completeness of reporting of RCTs. Reporting of RCTs published in journals that encourage authors to use the CONSORT Statement with those that do not is compared. We found that some items in the CONSORT Statement were fully reported more often when journals encouraged the use of CONSORT. While the majority of items are reported more often when journals endorse CONSORT, the data only showed a statistically significant improvement in reporting for five of 27 items. No items suggest that CONSORT decreases the completeness of reporting of RCTs published in medical journals. None of the evaluations included in this review used experimental designs, and their methodological approaches were mostly poorly described and variable when they were described. Furthermore, evaluations assessed the completeness of reporting of RCTs within a wide range of medical fields and in journals with a wide variation in the enforcement of CONSORT endorsement. Our results do have some limitations, but given the number of included evaluations and the number of assessed RCTs, we conclude that while most RCTs are incompletely reported, the CONSORT Statement beneficially influences their reporting quality.
+This update included 592 participants from seven studies (two new and one that had been excluded in the previous 2007 review). We found evidence from four small trials that incentive spirometry offers no advantage over standard post-surgical physical therapy, or preoperative education in preventing breathing complications and pneumonia, improving lung function, or shortening length of hospital stay in patients undergoing CABG. Bigger and better designed trials are needed to determine if there is any role for incentive spirometry.
+However, the review of trials found conflicting evidence about whether or not IPC is better than compression bandages and hosiery. Intermittent pneumatic compression (IPC) is better for healing leg ulcers than no compression. . Some studies suggest IPC might be a beneficial addition to bandages for some ulcers, but these studies might be biased. Delivering the IPC therapy in a rapid manner by inflating and deflating the IPC device more quickly resulted in more ulcers being healed than with a slower deflation regime.
+This review includes 18 randomised controlled trials with 10,171 women and looks at catgut and synthetic materials used to stitch the perineum after childbirth. It also includes a more recently produced material which has been specially designed to be absorbed more quickly. The main findings were that women stitched with synthetic materials had less pain in the first three days after delivery and needed fewer drugs to relieve pain in the 10 days after giving birth, compared with women stitched with catgut. There was evidence that synthetic stitches were not always readily absorbed and some women with these stitches needed them to be removed. Women experienced similar short and long-term pain with standard absorbable synthetic materials and more rapidly absorbing stitches. However, in one trial, fewer women with rapidly absorbing stitches reported using pain-relieving drugs during the 10 days after delivery, and there was less need for these stitches to be removed. When catgut and glycerol-impregnated catgut were compared the results were similar, although the latter was associated with more short-term pain. One trial examined monofilament and standard synthetic stitches and there was little difference between the two materials in terms of pain and wound healing. As well as the type of material used, other factors such as the technique used to carry out the stitching (using a continuous thread or a series of separately tied stitches) and the skill of the person carrying out the procedure, may also affect the amount of pain and the way perineal wounds heal.
+We found eight randomized controlled trials, of which five compared similar chemotherapy regimens in both trial arms, except for the anthracycline. Even among these five trials, three included more intense chemotherapy in the control arm. Most trials were conducted in the 1980s and 1990s. Only one of them included rituximab as part of the chemotherapy regimen. Almost all patients were treatment-naive with advanced disease. Follow-up ranged between three and five years in most trials. The main results from this set of trials are. 1. There is no evidence that OS is prolonged with the use of anthracyclines, although it may have been hampered by the more intense regimens given in the control arms of three of five trials. 2. Anthracyclines improved disease control. Concordantly, less patients progressed or relapsed within three years of treatment with ACR. 3. There is no statistically significant difference in complete or overall response rates. 4. Qualitatively, more side effects were reported with ACR, myelotoxicity and cardiotoxicity included. This evidence is limited, mainly due to disparities in regimens between control and study arms, but also since most included trials were conducted over one to two decades ago, and only one employed rituximab. Importantly, results from this study were in agreement with pooled-outcomes from trials of the pre-rituximab era. It is essential to find the optimal chemotherapeutic regimen in conjunction with rituximab and other novel agents, and understand the role of anthracyclines in this combination, especially with current methods that are able to reduce their toxicity. With longer follow-up periods we may better understand whether improved disease control will eventually translate to an increase in survival.
+We identified 12 randomised controlled trials that included 981 people; the evidence is current up to March 2015. The trials were mainly conducted in India. The studies were small and many of them were at risk of bias. They also looked at different treatments. This meant that for most treatments we could not draw any conclusions as to which was better. There was one exception. Three trials (434 participants) compared topical natamycin and topical voriconazole. In these trials there was low quality evidence that people receiving topical natamycin were more likely to be cured and were more likely to have better vision three months after treatment started. There was high quality evidence that people receiving natamycin were less likely to develop a hole in the cornea and need a transplant. We did not find any evidence on quality of life. One trial found evidence that natamycin was particularly good when treating a particular type of fungal infection (Fusariumspecies).
+We included three studies in this review with 385 participants in total with follow-up periods of different length. Two studies with 150 participants compared DHC to buprenorphine for detoxification (managing physical symptoms of withdrawal), while one study with 235 individuals compared DHC to methadone for maintenance substitution therapy (providing legal substance to reduce risk behaviour and other harm related to drug use over a longer period). All the studies took place in the UK. Our primary outcome was abstinence or no longer using illegal substances; our secondary outcomes were completing treatment, as well as health-related consequences of substance use, and other behaviours often linked to substance use such as illegal activity. We also assessed the safety of DHC. For detoxification from illegal substances such as heroin, DHC may not work any better than buprenorphine in reducing substance use, keeping individuals in treatment and other behaviours. The pattern stayed the same for follow-up appointments. For maintenance treatment, DHC also may not work better than methadone in reducing substance use or any of the secondary outcomes, but participants may be more likely to stay in treatment. This finding remained the same across longer follow-up periods as well. The only adverse event reported was one death from a methadone overdose in the study that compared DHC with methadone as maintenance therapy. The pattern of results indicates that individuals who received DHC generally may not do better in reducing their substance use, completing treatment or other measures of substance-related behaviours than those that received other types of medication. However it is premature to make definitive statements about the efficacy of DHC for reducing illegal substance use, due to the low quality of evidence. Overall, the evidence was of low quality. There were two major issues across the studies. There was no blinding of the participants or those who assessed the outcomes, so that they were aware of which group they were in. There was also a high level of participants who dropped out of two of the studies. All three studies were funded by government or research foundation organisations.
+This systematic review was conducted to assess how street lighting affects the occurrence of road traffic crashes and associated injuries. The authors searched for all controlled trials comparing the effects of new street lighting with unlit roads, or improved street lighting with the pre-existing lighting level. They found 17 controlled before-after studies, all of which were conducted in high-income countries. Twelve studies investigated the effects of newly installed street lighting, four the effects of improved lighting and one investigated both new and improved lighting. Five of the studies compared the effects of street lighting with a separate area control, while the remaining 12 used data from a day-time control. The authors were able to pool crash or injury data from 15 of the studies. The risk of bias in these studies was judged to be high. The results indicate that street lighting can prevent road traffic crashes, injuries and fatalities. This finding might be of particular interest to low and middle-income countries where the policy on street lighting is less developed and the installation of suitable lighting systems is less common than in high-income countries. However, further well designed studies are needed to determine the effectiveness of street lighting in middle and low-income countries.
+We included two studies with 128 participants. Study size ranged from 54 to 74 participants with an age range of 21 to 85 years. Both studies included men and women. Both studies compared herbal medicines (nutmeg or St John’s wort) to placebo and allowed continued use of painkillers. Both studies reported side effects. There were no reports from participants of any reduction in pain intensity of 30% or above and there was no observable reduction in the total pain score in response to either nutmeg or St John’s wort. There were also no reductions in dropout rates or number of side effects between the treatment and placebo. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident. Only two small studies met this review’s search criteria. Neither provided any high-quality evidence for either possible benefits or harms. We judged the evidence to be of very low quality. Thus, results from the studies contained in this review are very uncertain and prevent any meaningful conclusions. Larger, high-quality studies are needed to assess accurately if herbal products are of any benefit or have the potential to harm when used to treat adults with neuropathic pain.
+Endometriosis is a painful condition in which endometrial tissue grows outside the uterus. It potentially affects a woman's ability to conceive. Recent studies support the contributing role of inflammation in endometriosis-related pain. Since anti-TNF-α drugs can inhibit the inflammation process, they may relieve the symptoms of the disease without inhibiting ovulation. However, this systematic review included one randomised controlled trial and found that there was not enough evidence from which to draw conclusions about the effectiveness and safety of anti-TNF-α drugs in relieving pain in women with endometriosis. There was no evidence of an increase in adverse events in the anti-TNF-α drugs group compared with the placebo group.
+This review included evidence available up to 30 June 2014. Seven trials with low to moderate risk of bias were included: five in children (987 participants) and two in adults (156 participants). An eighth trial in 40 adults was at high risk of bias and did not provide any data for analysis. Although some studies in children followed participants for two or three years, reliable information is only available for up to about one year after surgery due to the high number of participants missing follow-up after the first year. Some studies had recruited children who were more severely affected by tonsillitis than other studies (for example, they had tonsillitis more often and with more severe symptoms). Therefore, we grouped the children into 'severely affected' and 'less severely affected' subgroups. Two studies in adults had a short duration of follow-up (five to six months following surgery). We found that in general children affected by recurrent acute tonsillitis may have a small benefit from adeno-/tonsillectomy: this procedure will avoid 0.6 episodes of any type of sore throat in the first year after surgery compared to non-surgical treatment. The children who had surgery had three episodes of sore throat on average compared to 3.6 episodes experienced by the other children. One of the three episodes is the episode of pain caused by surgery. When it comes to avoiding bad sore throats, children who have more severe or frequent tonsillitis may benefit more from surgery compared to less severely affected children. In less severely affected children the potential benefits of adeno-/tonsillectomy are more uncertain. There are no good quality data for the effects of surgery in the second or later years after surgery. We did not find enough evidence to draw firm conclusions on the effectiveness of tonsillectomy in adults with chronic/recurrent acute tonsillitis. Evidence is only available for the short term and is of low quality. The data are also difficult to interpret as the studies do not take into account the days of pain that always follow the operation. Based on the two small trials, tonsillectomy seems to result in fewer days of sore throat in the first six months after surgery. Two of the studies in children said that they could not find a difference in quality of life outcomes and one study could not find a difference in the amount of painkiller that children took to help with their sore throats. Bleeding immediately after tonsillectomy or in the two weeks following surgery is an important complication. The studies did not provide good information to allow us to assess accurately the risk of these complications. We judged the quality of the evidence to be moderate for the data on children (this means that further research is likely to have an important impact on how confident we are in the results and may change those results). Quality is affected by a large number of children who are 'lost to follow-up' after the first year of the study. In addition, some children who are assigned to the 'no surgery' group end up having surgery. The quality of evidence for tonsillectomy in adults in adults is low. As always, any potential benefits of surgery should be carefully weighed against the possible harms as the procedure is associated with a small but significant degree of morbidity in the form of bleeding (either during or after the surgery). In addition, even with good pain relief medication, the surgery is particularly uncomfortable for adults.
+This systematic review included results from 83 randomised controlled clinical trials evaluating 24 treatments, with a total of 10,036 participants diagnosed with actinic keratosis. We included 18 topical creams or gels applied to a skin area by the participants: adapalene gel, aretinoid methyl sulfone (Ro 14-9706), betulin-based oleogel, calcipotriol (vitamin D), colchicine, diclofenac, 2-(difluoromethyl)-dl-ornithine (DFMO), 5-fluorouracil, ß-1,3-D-glucan, imiquimod, ingenol mebutate (PEP005), isotretinoin, masoprocol, nicotinamide, resiquimod, sunscreen, DL-α-tocopherol (vitamin E), and tretinoin. One treatment, etretinate, was taken orally. Clinical staff administered two mechanical treatments (carbon dioxide and Er:YAG laser resurfacing) on a skin area, and they administered three chemical treatments: cryotherapy on individual lesions, photodynamic therapy on individual lesions or a skin area, and trichloroacetic acid peel on a skin area. The clinical effects resulting from the treatment of actinic keratoses were reported differently from one study to another. In spite of this inconsistency, it can be concluded that several good treatment options exist for the treatment of actinic keratoses. Actinic keratoses were successfully treated with cryotherapy, diclofenac, 5-fluorouracil, imiquimod, ingenol mebutate, photodynamic therapy, resurfacing, and trichloroacetic acid peel. These different treatments were generally comparably effective. Skin irritation was associated with some of these treatments, such as diclofenac and 5-fluorouracil, but other side-effects were uncommon. The final cosmetic appearance varies from one treatment to another. Imiquimod treatment and photodynamic therapy resulted in better cosmetic appearance than treatment with cryotherapy and 5-fluorouracil. Treatment with photodynamic therapy gives better therapeutic and cosmetic results than cryotherapy for individual lesions. For field-directed treatments, diclofenac, 5-fluorouracil, imiquimod, and ingenol mebutate are good options associated with different side-effects and cosmetic results. Thus, the choice of treatment option for actinic keratosis depends on the number of lesions, the individual's desired results, and tolerance to the treatments.
+We found one randomised controlled trial that met our inclusion criteria. This trial included 752 women who, following vaginal birth, had a tear to the skin between the vagina and anus that did not include the anal muscles on clinical examination. The women were allocated to receive either routine care (clinical examination) or anal ultrasound prior to their tear being sutured (stitched). We found that women who had anal ultrasound before undergoing perineal repair were about half as likely to suffer from severe anal symptoms. This difference was clear at less than six months and greater than or equal to six months after giving birth. Women were, however, more likely to have significant perineal pain at three months after birth if they underwent ultrasound examination. Solid stool incontinence and involuntary loss of gas (flatulence) were not clearly different between the two groups of women. There was also no difference in terms of maternal quality of life. The study did not report on the need for secondary repair of external anal sphincter, the number of women who reported pain during sexual intercourse, women's satisfaction with care or details relating to mode of birth in any subsequent pregnancy. It was not possible to look at how effective anal ultrasound examination was at detecting anal sphincter injuries because women with clinically-detected obstetric-related anal sphincter injury were excluded from the study. We assessed the included trial as being at low risk of bias as it was a well designed trial, but it involved a small number of women. More trials are needed in this area to further evaluate this intervention and inform future practice. We did not find any studies that used ultrasound after the tear had been sutured. It would be helpful if future studies could evaluate how effective ultrasound is at detecting obstetric anal sphincter injury. The cost of the intervention and any training needs should be considered, along with maternal quality of life and individual symptoms experienced by postnatal women. It would also be useful to examine how women give birth with subsequent pregnancies and longer-term outcomes.
+We found 106 studies, mostly assessing a single device, which analysed 16,260 eyes (8353 cases, 7907 controls). Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 patients) OCT. Twenty-four studies were sponsored by the manufacturer, and in 15 the study funding was unclear. The final diagnosis of glaucoma had to be confirmed by clinical examination, including visual field testing or clinical optic nerve examination or both. However, we could not find studies comparing two tests, the most robust way to test these instruments, and including a series of consecutive patients at risk as seen in routine care, as we had hoped. Rather, we found studies assessing the performance of a single test in people without glaucoma as opposed to its performance in people with a previous diagnosis of glaucoma. The study search is current to 19 February 2015. The performance of all devices was very variable across studies, but overall similar. In 1000 people referred by primary eye care, of whom 200 (20%) have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma (sensitivity 70%), and would incorrectly refer 50 out of 800 patients without glaucoma (at specificity 95%). If prevalence were 5%, for example, in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people. The tests were better at detecting more severe glaucoma compared to early glaucoma. The selection of two well-defined groups of healthy and glaucoma eyes in nearly all studies, rather than the use of these imaging tests in a series of patients at risk of glaucoma as in the real world, may overestimate the accuracy of these devices compared to what could be achieved in daily practice.
+This review identified nine studies (461 participants) comparing Huangqi type formulations with control drugs. The results of this review suggest that Huangqi type formulations may have a positive effect on nephrotic syndrome by increasing plasma albumin and reducing urine albumin excretion, blood cholesterol and triglycerides. Huangqi type formulation may reduce some adverse effects of other drugs used for treating nephrotic syndrome, however these were only reported in two studies. The methodological quality of the nine included studies was poor and was the major limitation of this review. The types of pathology, sex and age of the patients, as well as the duration and dosage of the Huangqi type formulations could not be analysed.
+The authors identified two trials that evaluated herbal medicines in PMS. One of these was a higher quality study that tested the traditional Chinese medicine decoction Jingqianping granule. This was shown to increase the rate of recovery from PMS symptoms. Because the formula for this herbal medicine was provided by the trialists themselves, the review authors recommend further trials to ensure that the results are reproducible with other formulations. Strong evidence in support of other herbal formulae for the treatment of PMS is currently lacking.
+participants. All but two of the studies were conducted in the USA. The other studies were in the UK and China. Follow-up periods varied from at  completion of the intervention to six years. The studies were too few and each intervention too different to draw any firm conclusions on whether  non-school based interventions prevent or reduce drug use by young people.The interventions with suggested benefits need further evaluation before it  can be firmly established that they are effective. One of two studies of motivational interviewing suggested that this intervention was beneficial on  self-reported cannabis use. Three family interventions (Focus on Families, Iowa Strengthening Families Program and Preparing for the Drug-Free Years)  were evaluated, in two separate studies, and may have been beneficial in preventing self-reported cannabis use. The latter two programs were  compared to the school-based Life Skills Training program. All of the eight studies of family interventions included contact with parents, in family  groups or in separate sessions for parents and their children. Multicomponent community interventions did not have any strong effects on  drug use. There were five studies, four of which added the community component to a school drug education program. Education and skills training  was not effective in two studies.  Many of the studies lacked blinding and had high numbers of participants lost to follow up. No study reported cost outcomes.
+However, trials that might address this issue have not been done and there is therefore some uncertainty about their usefulness. Since patients can experience side-effects when taking these drugs, the risks of these have to be balanced with the unknown prospect of benefit when considering whether to use them in Ramsay Hunt syndrome.
+We searched for evidence on 29 February 2016 and identified a further 31 new trials for inclusion in the review. This updated review now includes 100 randomised controlled studies involving more than 83,246 women. The 73 trials that contributed to the analyses were from 29 countries and involved 74,656 women. Some 62% of the women were from high-income countries, 34% from middle income countries and 4% from low-income countries All forms of extra organised support analyzed together showed an increase in the length of time women continued to breastfeed, either with or without introducing any other types of liquids or foods. This meant that fewer women stopped any breastfeeding or exclusively breastfeeding (moderate quality evidence) before four to six weeks and before six months. Both trained volunteers and doctors and nurses had a positive impact on breastfeeding. Factors that may have contributed to the success for women who exclusively breastfed were face-to-face contact (rather than contact by telephone), volunteer support, a specific schedule of four to eight contacts and high numbers of women who began breastfeeding in the community or population (background rates). The term 'high-quality evidence' means that we are confident that further studies would provide similar findings. No outcome was assessed as being 'high-quality'. The term 'moderate-quality evidence' means that we found wide variations in the findings with some conflicting results in the studies in this review. New studies of different kinds of support for exclusive breastfeeding may change our understanding of how to help women to continue with exclusive breastfeeding. The methodological quality of the studies was mixed and the components of the standard care interventions and extra support interventions varied a lot and were not always well described. Also, the settings for the studies and the women involved were diverse. Providing women with extra organised support helps them breastfeed their babies for longer. Breastfeeding support may be more helpful if it is predictable, scheduled, and includes ongoing visits with trained health professionals including midwives, nurses and doctors, or with trained volunteers. Different kinds of support may be needed in different geographical locations to meet the needs of the people within that location. We need additional randomised controlled studies to identify what kinds of support are the most helpful for women.
+This review found five trials of ITNs in pregnant women. The four trials in sub-Saharan Africa compared ITNs with no nets and showed a benefit from ITNs in terms of fewer malaria infections, low birthweight babies, and fewer babies died before delivery. The effects on severe anaemia in the mothers were inconclusive. The one trial from Asia compared ITNs with untreated nets and showed a beneficial effect on anaemia in women and fewer babies died before delivery, but it had no impact on other outcomes. ITNs have been shown to be beneficial and should be included in strategies to try to reduce the adverse effects of malaria in pregnant women in endemic areas of the world.
+This review included five randomised controlled trials involving 244 participants. A combined analysis of trials using our primary outcome showed that the 'risk' of success in a patient who received radiotherapy was 1.92 times that of a patient who did not receive radiotherapy. Single studies suggested that orbital radiotherapy in combination with steroids had a better outcome than steroids alone. There was no significant change in quality-of-life information collected in the orbital radiotherapy groups compared to the other groups. The short-term adverse events reported in the trials were mild and localised to the area of treatment (redness of skin and temporal hair loss). However, trial methodology may have led to a decreased rate of adverse events from radiotherapy. Three trials excluded diabetic patients and these patients have been reported, in the literature, to be at higher risk of developing radiation retinopathy and of having progression of pre-existing diabetic retinopathy. Some studies did not report on retinal changes at all.
+We searched the literature for randomised controlled trials up to 23 September 2013, and included 71 trials. The included studies compared chlorpromazine with three newer antipsychotics: risperidone, quetiapine or olanzapine. Most included trials were short term studies and undertaken in China. Based on low quality evidence, we found that chlorpromazine is not much different to risperidone or quetiapine but is associated with more side effects. More favourable results were found for olanzapine with those receiving olanzapine experiencing fewer side effects and greater improvements in global state and quality of life than those receiving chlorpromazine, but again this is based on low quality evidence. Larger, longer, better conducted and reported trials should focus on important outcomes such as quality of life, levels of satisfaction with treatment or care, relapse, costs and hospital discharge or admission. Also, more international studies are needed. Outpatient treatment was under-represented in the included studies, and future research should also include work with this group of people. Due to the limitations of evidence in this Cochrane review, it is difficult to draw firm conclusions. Chlorpormazine is available widely, is comparable with the newer antipsychotics and is relatively cheap so despite its propensity to cause side effects, is likely to remain one of the benchmark antipsychotics. The plain language summary has been written by a consumer. Ben Gray: Senior Peer Researcher, McPin Foundation. http://mcpin.org/.
+The evidence is current to May 2017. We found 1 study including 45 participants with MCI with a follow-up of 4 years; gender was not reported and the median age for those with a PET-positive scan by quantitative assessment was 73.5 years old. For those with a PET-negative scan the mean age was 71.8 years old. Participants were mainly recruited from local memory clinics. Study funding sources: the study was funded by the test manufacturer. The main limitation of this review was that our findings were based on only one study, with not enough details on how the participants were selected. The study was considered to be at high risk of bias, since the final ADD diagnosis was not established separately from the scan results, and due to potential conflicts of interest detected. In this review, based on only one study, we found that the18F-florbetaben PET scan, as a single test with visual assessment, correctly classified 100% of the participants who will progress to ADD and 83% of the participants who did not progress to ADD at four years follow-up. This means that in a cohort with 100 participants with MCI, 47 of whom will progress to ADD, we would expect that all those 47 MCI participants would test positive with the18F-florbetaben scan and that 0 participants would be falsely negative (i.e. none of the 47 participants would have a negative test and yet progress to ADD). In addition, we would expect 44 of 53 participants who did not progress to ADD to be18F-florbetaben-negative and 9 to be falsely positive (i.e. 9 of the 53 participants would have a positive test but not progress to ADD). The small size of the included study lowered our confidence on these estimates of accuracy and it is still possible that the test is considerably less accurate than these results suggest. We conclude that 18F-florbetaben imaging is a promising test to predict the progression from MCI to ADD; however, we need more studies to clearly demonstrate its accuracy.
+The evidence in this review is current up to 14 September 2016. 39 studies were included with a total of 3520 participants. Participants were male and female, all ages and ethnic origins, out patients or in patients, who were scheduled to have radiation therapy with or without chemotherapy to the head and neck. Drugs included were any prescribed to prevent salivary gland problems and given before or during radiotherapy. Information was collected from the end of radiotherapy except for that about adverse effects. Different techniques for giving radiation treatment that might reduce damage were not included. The main outcomes measured were participant's own assessment of dry mouth and the measurement of salivary flow. Secondary outcomes measured included adverse or unwanted effects such as sweating, crying, watery discharge from the nose, diarrhoea and nausea. There is some low-quality evidence to suggest that the drug amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months after radiotherapy). However it is less clear whether or not this effect is sustained to 12 months after radiotherapy. The benefits of amifostine should be weighed against its high costs and side effects. Adverse effects of vomiting, low blood pressure, feeling of sickness and allergic response were all more frequent in those receiving amifostine. There was insufficient evidence to show that any other treatment is beneficial. The quality of evidence for amifostine was found to be low because of risk of bias, inconsistency and imprecision caused by the small number of studies in the comparison or sample size. A standardized scale for measuring participant's experience of dry mouth would in future allow comparison and pooling together of results.
+This systematic review focused on randomised studies evaluating the antitumour effects of anthracycline therapy. The authors found that at the moment no high quality evidence is available which shows that the use of anthracyclines has an increased antitumour effect in acute lymphoblastic leukaemia (ALL) as compared to treatment without anthracyclines, but there was some suggestion that this might be the case. Further high quality studies are needed to provide a definitive conclusion. For Wilms' tumour, rhabdomyosarcoma and undifferentiated sarcoma, Ewing's sarcoma, non-Hodgkin lymphoma, hepatoblastoma and acute myeloid leukaemia (AML) the review authors found only limited data and were unable to draw conclusions. Also, there were no data for other childhood cancers. More high quality research is needed. At the moment there are five ongoing or unpublished randomised studies evaluating the use of anthracyclines in the following types of childhood cancer, hepatoblastoma, ALL (two studies), rhabdomyosarcoma, and Wilms' tumour.
+We searched the databases until October 2014. We included 85 studies, 82 of which (10,350 participants) were eligible for quantitative analysis. The study participants were randomly selected to receive either intravenous lidocaine injection or normal saline (placebo) at the same time as the propofol injection. We reran the search in November 2015. We found 11 potential studies of interest, those studies were added to the list of ‘Studies awaiting classification' and will be fully incorporated into the formal review findings when we update the review. Three out of the 85 studies were funded by either a pharmaceutical manufacturer with a commercial interest in the results of the studies or the company which supplied the propofol. Eight studies were supported by government hospital or university funds and one study was funded by a charitable grant. We found that the injection of lidocaine into a vein, either mixing lidocaine with propofol or injecting lidocaine before propofol, could effectively reduce the incidence and the high levels of pain associated with the injection of propofol. Adverse effects such as inflammation (redness, swelling) of the vein at the injection site were rare and in two studies were not more frequent with the use of lidocaine. No study reported on patient satisfaction. Based on these results we would expect that out of 1000 patients receiving intravenous propofol, about 384 who did not also receive intravenous lidocaine, would experience moderate to severe pain, compared to only 89 patients who also received intravenous lidocaine. The overall quality of evidence was high with a very large beneficial effect obtained by the administration of lidocaine to reduce painful propofol injections.
+From extensive searches conducted on 8 March 2017, we identified two relevant randomised controlled trials (RCTs), which are the fairest tests of treatment. There were 121 participants in these two trials, which compared blood-thinning 'anticoagulant' drugs (heparin in one and enoxaparin in the other) delivered by injections under the skin versus no anticoagulant drug soon after ICH. The primary outcome of this review was the combined risk of several important clinical outcome events (such as another intracerebral haemorrhage, ischaemic stroke, or death from a cardiovascular cause). We were not able to calculate this outcome for the included studies. Neither RCT reported on recovery of independence or mental abilities. One RCT involving 46 participants reported on case fatality associated with short-term antithrombotic treatment, and did not find a statistically meaningful effect. For the consequences of treatment that could be analysed, the risk estimates were imprecise and uncertain. Therefore, the potential benefits and harms of antithrombotic drugs soon after a stroke due to bleeding in the brain remain unclear. New high-quality RCTs investigating the use of antithrombotic treatment after stroke due to ICH appear justified and are needed. The overall quality of the evidence was low. This is due to the way the included trials were conducted and reported, as well as the small number of participants, which may not have been high enough to detect small differences between the antithrombotic treatment and no antithrombotic treatment groups.
+There was not a significant effect on weight gain in the one randomized controlled trial identified that investigated addition of lactase. The review authors searched the medical literature thoroughly but found only this one high quality trial enrolling 130 preterm infants. No adverse effects were noted and lactase treated feeds appeared to be well tolerated.
+We identified randomized controlled trials evaluating the benefits and side effects of nitrates by searching major databases for original articles until June 2014. We included 27 studies (8244 participants) in this review. All participants were older than 15 years. Most trial participants had low to mild risk of perioperative cardiac complications. We reran the search in January 2016. We added three potential new studies of interest to the list of ‘Studies awaiting classification' and will incorporate them into our formal review findings for the review update. We examined the following results: death for any reason, angina pectoris (sensation of chest pain due to a restriction in blood supply to heart muscle), acute myocardial infarction (stop in the flow of blood to part of the heart, causing damage to the heart muscle), cardiac ischaemia (restriction in blood supply to heart tissue), acute heart failure (loss of heart function), cardiac arrhythmia (irregular heartbeat), cardiac arrest (sudden stop in effective blood circulation due to failure of the heart) and increased troponin (a biomarker of heart disorder). We also evaluated adverse events, such as low blood pressure, headache, fast heartbeat and nausea and vomiting. We found no significant differences between nitrates and controls, with the exception of nicorandil versus placebo (one study, 248 participants). Nicorandil appeared to decrease the incidence of cardiac ischaemia. We used GRADE criteria to assess the overall quality of evidence as very low for the main results owing to risk of bias, insufficient data and imprecision. Available evidence is insufficient to show whether nitrates are associated with improved mortality and cardiac complications in patients during non-cardiac surgery. Well-designed trials are needed in this field.
+Review authors from the Cochrane Oral Health Group carried out this review of existing studies and the evidence is current up to 8 October 2014. The review includes six studies published from 1967 to 1997, which involved 252 children as participants (although data were supplied on only 246 of the children). Three of the studies were carried out in the USA, one in Canada, one in Sweden and one in Australia. Not all of the studies gave the ages of children involved; in four of the studies children were aged from two and a half to 18 years old, in one study they were aged four years and over and in another nine years and over. Use of an orthodontic brace (such as a palatal crib or arch) or a psychological intervention (such as use of positive or negative reinforcement), or both, was more likely to lead to cessation of the habit than no treatment. Most of the trials that compared two different interventions were inconclusive but one study suggested that, of two different types of braces,a palatal crib is more effective than a palatal arch design. The evidence presented is of low quality due to the small number of participants in the few available studies and problems with the way in which the studies were conducted. There was a high risk of bias across the studies. Orthodontic braces or psychological intervention seems to be effective to help children stop sucking that does not have a feeding purpose but the evidence is low quality. Further high quality clinical trials are required to guide decision making for what is a common problem that can require lengthy and expensive dental treatment to correct.
+To date, data obtained from one well-designed randomised clinical trial suggest that inserting a cervical pessary is superior to expectant management in the prevention of preterm birth in 385 women between 18 and 22 weeks of pregnancy. Neonatal paediatric care admission was reduced in the pessary group in comparison to the expectant group. These women had a singleton pregnancy and high risk of preterm birth because of the short length of the neck of the womb (cervix). Among the pessary group, 27 women needed pessary repositioning without removal and there was one case of pessary removal. Results of both the randomised trial and non-randomised trials show that pessary users complained of increased vaginal discharge. More studies are needed in different settings, with singleton and multiple pregnancies where the weakness of the cervix is from other causes, to confirm the results of the single trial included in this review. Some studies are ongoing.
+The review of trials (mostly in children) found that pedestrian safety education can improve children's road safety knowledge and their observed road crossing behaviour. Education may need to be repeated at regular intervals, as the effect can decline with time. However, whether these changes to knowledge or behaviour can be linked to a reduction in pedestrian deaths and injuries is unknown.
+The evidence from this review, which included findings from 29 randomised controlled trials (4974 participants in total), suggests that mirtazapine is likely to have a faster onset of action than the most frequently used type of antidepressants, which are the selective serotonin reuptake inhibitors (SSRIs). It would appear that mirtazapine is superior to SSRIs at the end of treatment over 6 to 12 weeks. Mirtazapine causes adverse events that lead to a similar frequency of dropouts as SSRIs and tricyclic antidepressants, although adverse event profile of mirtazapine is unique. Mirtazapine is likely to cause weight gain or increased appetite and somnolence but is less likely to cause nausea or vomiting and sexual dysfunction than SSRIs.
+After thorough search of the available literature, we found fifty-four observational studies (fifty one meta-analysed) including 943,728 patients that addressed either the volume-outcome relationship in the context of modern colorectal cancer treatment, or the effects of surgeon specialization. The results confirm the presence of a volume-outcome relationship in colorectal cancer surgery, based on hospital and surgeon caseload, and benefits for specialization. For death within five years of treatment, hospital volume appeared to be more beneficial in rectal cancer surgery than for colon cancer. However, international differences in the data suggest provider variability at the hospital level between the different countries, making it imperative that every country or healthcare system must establish audit systems to guide changes in the service provision based on local data, and facilitate centralization of services as required. Overall quality of the evidence was low as all included studies were observational by design. In addition there were discrepancies in the definitions of caseload and colorectal specialist. However ethical challenges associated with the conception of randomised controlled trials addressing the volume outcome relationship makes this the best available evidence.
+This systematic review compared different techniques of surgical repair for anterior shoulder instability. Only three randomised controlled trials, involving a total of 184 people with anterior shoulder instability that usually followed a traumatic event, are included in the review. All three trials compared arthroscopic (key hole) surgery with open surgery, generally involving the repair of Bankart lesions. All three trials were inadequately reported but appeared well-conducted with minimum follow-ups of two years. The limited data available showed no statistically significant differences between the two groups in recurrent instability or re-injury, in subsequent instability-related surgery or surgery for all reasons. Data for other outcomes, including shoulder function, also showed no significance differences between the two groups. In all the available evidence was insufficient to draw conclusions and further well designed randomised controlled trials are required.
+The evidence is current to March 2016. In this review we identified four randomised controlled trials, three trials are still recruiting participants and are due to complete recruitment by February 2018. The completed trial (58 participants) compared plasma transfusion to no plasma transfusion prior to central line insertion. There was not enough evidence to determine whether plasma transfusions affected minor or major procedure-related bleeding. The included study did not report the number of people dying due to any cause, the number of people receiving red cell or plasma transfusions, the occurrence of transfusion or line-related complications, length of time in hospital, correction of clotting abnormalities, or quality of life. The quality of the evidence is very low because this review includes only one small study. The ongoing studies (expected to recruit 355 participants in total) will be unable to provide sufficient data for this review’s primary outcomes because major bleeding and mortality are uncommon. We would need to design a study with at least 4634 participants to be able to detect an increase in the number of people who had major bleeding from 1 in 100 to 2 in 100. It is not possible from the current randomised controlled trial evidence to recommend whether or not prophylactic plasma transfusion is beneficial or harmful in this situation.
+This review compares acute day hospital care to inpatient care. We found that at least one in five patients currently admitted to inpatient care could feasibly be cared for in an acute day hospital. Patients treated in the day hospital had the same levels of treatment satisfaction and quality of life as those cared for as inpatients. The day hospital patients were also no more likely to be unemployed at the end of their care.
+We included three trials, with a total of 47 patients, one of these was in young children and there were both children and adults in other two. These trials looked at the effects of drugs (megesterol acetate and cyproheptadine hydrochloride) compared to a placebo (a tablet that contained no medicine) to stimulate appetite. The trials lasted between three and six months. We found that, in the short term (up to six months), these drugs may improve weight and appetite. There was no effect seen on lung function. All stimulants may have adverse effects which can worsen cystic fibrosis, such as the effects on blood sugar control, fatigue, mood, fluid retention, the liver and shortness of breath, but unfortunately accurate evidence for how often these symptoms occurred was not always reported in the same way. The trials we found were too small to show if megesterol acetate and cyproheptadine hydrochloride can improve weigh and appetite safely. While there is evidence to suggest that appetite stimulants can improve weight and poor appetite in adults and children with cystic fibrosis, we believe more research is needed to identify appropriate ways of measuring appetite and then to collect sound data from enough patients to find out if appetite stimulants can improve appetite safely in cystic fibrosis. We are happy that in two of the three trials, volunteers had equal chances of receiving appetite stimulants or placebo, but we are not sure if this is true for the third trial. It was not clear to us whether volunteers or their clinicians would be able to work out which group they were going to be put into. We believe that none of the volunteers or their clinicians could tell if they were receiving appetite stimulants or a placebo. Volunteers withdrew from two studies and we have some concerns about the reasons for this. We also have some concerns that some of the outcomes that the trial was going to measure were not reported in the published results.
+The efficacy of galantamine has been tested in two randomised controlled trials for the treatment of vascular dementia and for a mixed population of Alzheimer's disease patients with evidence of cerebrovascular disease on scanning. The rationale behind its use is to correct the cholinergic deficit seen in vascular dementia. This review found evidence of benefit for galantamine compared with placebo in measures of cognition in both studies. Both studies indicated higher rates of nausea and vomiting in patients taking galantamine compared with placebo.
+Our search for eligible papers was updated in August 2014 and we found one trial with 26 adult participants in Spain. The study sought to test if hepatitis B virus vaccine was better than placebo in preventing PLHIV from getting hepatitis B. The single study in this review showed improved immunity against hepatitis B among people living with HIV and taking antiretroviral therapy at 12 months. This immunity was lost once they stopped taking antiretroviral therapy. No side-effects were reported. The quality of evidence was assessed as very low.
+We reviewed the evidence on the effect of pulse oximeters on outcomes of surgical patients. In this update of the review, the search is current to June 2013. We identified five studies in which a total of 22,992 participants had been allocated at random to be monitored or not monitored with a pulse oximeter. These studies were not similar enough for their results to be combined statistically. Study results showed that although pulse oximetry can detect a deficiency of oxygen in the blood, its use does not affect a person's cognitive function and does not reduce the risk of complications or of dying after anaesthesia. These studies were large enough to show a reduction in complications, and care was taken to ensure that outcomes were assessed in the same way in both groups. The studies were conducted in developed countries, where standards of anaesthesia and nursing care are high. It is possible that pulse oximetry may have a greater impact on outcomes in other geographical areas with less comprehensive provision of health care.
+The review authors identified eight controlled trials in which a total of 2222 adults were randomised to have balloon angioplasty or drug treatment only. The overall quality of the evidence was considered to be moderate because the methodological quality of the studies varied substantially and two of the studies had not provided sufficient data to be able to assess their risk of bias. Overall, the data were insufficient to show that one treatment was better than the other for preventing loss of kidney function or restenosis of the renal artery. Those treated with balloon angioplasty may require fewer antihypertensive drugs or lower doses and experience a slight improvement in diastolic but not systolic blood pressure. Balloon angioplasty appears to be safe and there were similar numbers of renal and cardiovascular adverse events in participants treated with either approach. A small number of procedural complications of balloon angioplasty were reported (collection of blood outside the blood vessel at the site of catheter insertion (6.5%), dilated groin artery (0.7%), renal artery or kidney perforation or tear (2.5%) as well as deaths shortly before, during or after the procedure (0.4%)). No side effects of medical therapy were reported.
+The studies varied in the content of what parents were trained to do, and over what length of time parents had contact with professionals. Parents received training either individually with their child or in groups with other parents. In the majority of the studies, the interventions aimed to help parents be more observant and responsive during interactions with their child in order to help their child develop communication skills. In summary, the review finds sufficient evidence that the ways in which parents interacted with their children did change as intended. The review also suggests improvement in child outcomes such as understanding of language and severity of autism characteristics as a result of interventions delivered by parents. However, important outcomes such as other aspects of children's language, children's adaptive skills and parent stress did not show change. The evidence is not yet strong for any outcome and would benefit from researchers measuring effects in the same ways.
+Based on 35 clinical trials involving 1,997 newborns, it can be concluded that DPNB and EMLA do not eliminate circumcision pain, but are both more effective than placebo or no treatment in diminishing it. Compared head to head, DPNB is substantially more effective than EMLA cream. Ring block and lidocaine creams other than EMLA also reduced pain but did not eliminate it. Trials of oral acetaminophen, sugar solutions, pacifiers, music, and other environmental modifications to reduce circumcision pain did not prove them effective. DPNB can cause minor bruising, bleeding, or swelling at the injection site. EMLA and other lidocaine creams can cause skin color changes or local skin irritation. There is a rare risk with lidocaine creams of causing methaemoglobinaemia (blue-baby syndrome, where the baby's blood lacks sufficient oxygen). However, two trials of EMLA for circumcision pain relief measured methaemoglobin levels and found them normal. The circumcision procedure itself, especially without pain relief, can cause short term effects such as choking, gagging, and vomiting. Long term effects of circumcision without pain relief are not well understood. Strict comparability between trials was rare. Trials used a variety of indicators to measure baby's pain. Crying time, facial expression, and sweating palms can indicate infant pain, as can increased heart rate, breathing rate, and blood pressure. Levels of chemical indicators that can be part of a pain or stress response and are present in the blood or saliva are another gauge of pain levels. Also, procedures were not generally performed in just the same way in different trials. Type of clamp used (8sing a Mogen clamp can shorten the duration of the procedure), length of wait time after injection or application of anesthetic and procedure techniques varied.
+The last search for trials for this review was 19 February 2018. We assessed the evidence from 11 randomised controlled clinical trials comparing sodium valproate to phenytoin and we were able to combine data for 699 people from five of the 11 trials; for the remaining 450 people from six trials, data were not available to use in this review. Key results This review of trials found no difference between these two drugs for the seizure types studied for the outcomes of treatment failure (withdrawal from treatment) and controlling seizures (recurrence of seizures or achievement of a seizure-free period (remission) of 6 months or 12 months). The review also found no evidence to support or refute the policy of using sodium valproate for generalised onset tonic-clonic seizures and phenytoin for focal onset seizures. However, up to 49% of people within the trials classified as having generalised seizures may have had their seizure type wrongly diagnosed and these people may have been experiencing focal seizures or an uncertain seizure type, and this misclassification may have influenced the results of this review. We were unable to address the issue of preferring sodium valproate for generalised onset seizure types other than tonic-clonic, such as absence or myoclonic seizures. Quality of the evidence We judged the quality of the evidence as moderate to low for the evidence of treatment failure, moderate for remission outcomes and low for seizure outcomes as it is likely that misclassification of seizure type influenced the results of the review. Within four of the five trials providing data for this review, the design of the trial meant that the people and treating clinicians knew which medication they were taking. This design may have influenced the results. Conclusions Sodium valproate and phenytoin are commonly used treatments for individuals with epilepsy, but we found no difference between these treatments for the outcomes of this review or between seizure types. More information is needed and we recommend that all future trials comparing these medications, or any other antiepileptic medications, should be designed using high-quality methods. Seizure types of people included in trials should also be classified very carefully to ensure that the results are also of high quality.
+Five clinical studies assessed smoking cessation, with statistical combination of the results revealing no statistically significant effects on smoking cessation in either the short-term (< six months) or long term (> six months). Two clinical studies assessed dietary behaviour and showed that communicating genetic test-based risk estimates did change people's behaviour.The two studies assessing physical activity and the one study assessing medication or vitamin use aimed at reducing disease risks did not show that communicating DNA-based disease risk estimates had an effect on behaviour. For the six analogue studies, statistical combination of the results revealed a statistically significant effect of genetic test based disease risk estimates on intention to change behaviour only. There was no evidence of any unintended detrimental effects on motivation or mood. In summary, the limited amount and quality of evidence currently available suggests that communicating genetic test based disease risk estimates may have little or no effect on behaviour, but may have a small effect on intentions to change behaviour. Larger and better quality trials are needed.
+The review of trials found that using corticosteroids for lung sarcoidosis leads to some short-term benefit in terms of chest x-ray, but there is limited evidence that this benefit lasts or affects the long term outcomes of the disease.
+We identified four trials which compared FOBT to no screening and five trials which compared flexible sigmoidoscopy to no screening. No studies compared the two methods directly. Mortality from colorectal cancer was reduced with FOBT screening and screening with flexible sigmoidoscopy. When we compared the two methods, we could not conclude that one was better than the other. No complications occurred after the FOBT test itself, but 0.03% of participants suffered a major complication after follow-up. Among more than 60,000 flexible sigmoidoscopy screening procedures and almost 6000 work-up colonoscopies, a major complication was recorded in 0.08% of participants. These findings should be interpreted with caution as the reporting of adverse effects was incomplete.
+The search was carried out 15 November 2012 and resulted in identification of four potential studies, but none could be included. Three of these were excluded because they involved clozapine-related hypersalivation. The fourth study was excluded because it involved people with mood or other mental disorders and Chinese medicines. Dribbling or hypersalivation is an important problem that needs to be investigated via well-designed research and randomised trials. Until such time, psychiatrists and patients are likely to continue their treatment of hypersalivation on the basis of daily clinical judgement and personal experience rather than hard evidence. Treatment of hypersalivation caused by antipsychotics or neuroleptics other than clozapine does not seem to have received adequate research attention to help guide practice. The review authors conclude that using anticholinergics to treat dribbling or hypersalivation caused by antipsychotic drugs other than clozapine cannot be justified without further study. This plain language summary has been written by Benjamin Gray, Service User and Service User Expert: Rethink Mental Illness. Email: [email protected]
+Several small studies have assessed the benefit of providing drugs such as human growth hormone and glutamine in an attempt to improve intestinal function and wean intravenous nutrition (liquid food). The results of this review of 5 small studies suggest that human growth hormone used with or without glutamine may provide short term benefit for patients with short bowel syndrome in terms of weight gain and intestinal absorption of nutrients. However the benefits of treatment do not continue after treatment is stopped. Common side effects of treatment include peripheral edema (swelling of tissues, usually in the lower limbs), and carpal tunnel syndrome (numbness and muscle weakness in the hand). Conclusive evidence is not available to recommend this treatment. Further studies that evaluate human growth hormone treatment during the immediate phase of bowel adaptation are needed.
+This review is up-to-date as of 1 February 2019. The review includes 10 studies but we could only use the information from nine studies involving 1798 randomised people. We have asked for more information about one study. The review looks at eight different ways of applying fluoride to the teeth. People taking part in the studies were all having treatment with fixed braces. The number of people with new decay on the teeth at end of fixed brace treatment, as well as the amount of decay in each person, were measured and counted. We compared the following treatments: - dentist or nurse-applied fluoride e.g. varnish, gel or foam, - patient-applied/used fluoride e.g. toothpaste, mouthwash, gel or foam, and - materials that release fluoride over time e.g. glues, elastic bands. One study showed that when the dentist applies a foam with a high level of fluoride in it onto the teeth every time the patient is seen, this might reduce the risk of new decay. Another study found that if patients use a toothpaste with a higher level of fluoride than normal, then this might also reduce the risk of new marks on their teeth. No studies have shown that other ways of giving the teeth extra fluoride reduced the number and/or size of new decay on teeth in people wearing fixed braces. Harmful effects of the different ways of giving the teeth more fluoride were not reported in any of the included studies. The level of belief we have in these findings is low, due to the lack of studies testing the same fluorides and showing the same results. We suggest that more, well-conducted studies should be done in this area.
+We included 12 trials (five new for this update) that investigated the success of surgical treatment for oral cancers. The studies involved 2300 participants, 2148 of whom had mouth cancers. The trials included seven comparisons of different treatment options. None of them compared different surgical approaches for cutting out the primary tumour. The findings of the studies are mixed and it is not possible to draw firm conclusions about the optimal surgical approach for mouth and throat cancers. Surgical removal of the lymph nodes in the neck that appear to be cancer-free, at the same time as the cancer is removed did not seem to be associated with longer survival in two studies whose results were combined. Another study, however, suggested there may be a benefit of early neck surgery in terms of overall survival and 'disease-free survival' (length of time after primary treatment without signs and symptoms of disease). One study found cancer recurrence at or around the same site was less likely with the early surgery, while three other studies did not favour either treatment. There was no evidence that removal of all the lymph nodes in the neck resulted in longer survival compared to selective surgical removal of affected lymph nodes. One study evaluated use of a special scan (positron-emission tomography-computed tomography (PET-CT)), after a combination of chemotherapy and radiotherapy, to guide decisions about neck dissection, and found no difference in mortality (death) compared with undertaking a planned neck dissection before or after chemoradiotherapy. There were a number of other surgical approaches compared in the studies, but we were unable to use the results in this review. Although removal of lymph nodes from the neck is known to be associated with significant negative effects related to appearance and functions such as eating, drinking and speaking, the studies reported poorly on these side effects and did not measure quality of life accurately enough or in large enough numbers to be included in any of our analyses. The certainty of the evidence was very low as there were few studies for each comparison and they were at risk of bias because of the way they were designed. Some comparisons and outcomes had no useable results.
+This review found that inhaled corticosteroids used alone or in combination with systemic corticosteroids helped to relieve asthma attacks, were well tolerated and had few side effects. However, the most effective drug and dosage are unclear. The studies in the review included a variety of ICSmedications: beclomethasone (Beclovent/Becloforte/QVAR), budesonide (Pulmicort), dexamethasone sodium phosphate, fluticasone propionate (Flovent or Flixotide), Flunisolide (Aerobid) and triamcinolone (Azmacort). The review also found that ICS administered in this setting resulted in fewer hospital admissions. There was a reduction from 32 to 17 hospital admissions per hundred patients treated with ICS agents compared with placebo. At this time there is insufficient evidence to support using ICS agents alone as a replacement for systemic corticosteroid therapy in acute asthma attacks However, there are many unanswered questions about the use of ICS in the emergency department treatment setting. Future research should focus on optimal dosage, dosage frequency and delivery device, identification of effective ICS agents, clearly defined outcomes (such as admissions criteria, pulmonary function testing and follow-up after discharge from emergency departments).
+Two randomised studies, with moderate overall quality of evidence, comparing deferasirox to deferoxamine were identified. The evidence is current to 02 August 2013. The studies with 203 and 212 participants lasted for 12 months and 24 weeks, respectively. Only little data on patient-important outcomes such as mortality (limited by a short study follow up) and end-organ damage (incidence of diabetes mellitus) were available. Iron removal, as measured by the surrogate marker serum ferritin was significantly greater with deferoxamine. In one study, both drugs were reported to work equally well in reducing liver iron concentration. The safety of deferasirox was acceptable; the main side effects when compared to deferoxamine were increased frequency of nausea, diarrhoea and rash as well as a mean increase of creatinine, while adverse events of any kind were observed more often in people treated with deferoxamine. Patient satisfaction and compliance with therapy was significantly greater with deferasirox. The overall quality of evidence rated according to the GRADE criteria was moderate due to issues with study design. For four outcomes, namely liver iron concentration, serum ferritin, creatinine increase and satisfaction with treatment, it was judged as 'moderate' quality; for one outcome (discontinuations) was judged as 'low' quality. In summary, the evidence from the two included studies suggests that deferasirox is similarly effective as deferoxamine depending on the appropriate ratio of doses of deferoxamine and deferasirox being compared. In the short term, deferasirox appears to have an acceptable safety profile, but there are no comparative data based on randomised controlled trials available looking at long-term safety. Further data on long-term efficacy on patient-relevant outcomes and long-term adverse effects are needed to decide whether deferasirox should be used as alternative to the first-line option of deferoxamine. Currently, its use seems to be mainly warranted as a treatment option for people with sickle cell disease who cannot tolerate or comply with deferoxamine.
+Eight trials met the criteria for inclusion. It was not possible to pool the data because the trials studied different populations, tested folic acid in different doses, and used different outcome measures. There were two trials of folic acid in conjunction with B12. The analysis showed significant benefit of folic acid over placebo in some measures of cognition in a long-term trial recruiting elderly people with high homocysteine levels from a general population. In one pilot trial, 1 mg/day of folic acid was associated with significant improvement in behavioural response to cholinesterase inhibitors in people with Alzheimer's disease.
+The review of trials found no evidence that unopposed oestrogen and combined oestrogen and progestogen have an effect on body weight additional to that usually gained at the time of menopause. The review did not find any evidence that HRT prevents weight gain experienced at menopause.
+We included nine studies in which a total of 655 people (657 eyes) were enrolled. Participants had glaucoma and age-related cataract, and each study compared combined cataract and glaucoma surgery versus cataract surgery alone. Seven trials were conducted in Europe, one in Canada and South Africa, and one in the United States. Three trials were conducted at multiple centers, and the follow-up period ranged from 12 to 30 months after surgery. The evidence is current to 3 October 2014. We concluded from the available evidence that combined glaucoma and cataract surgery may lead to slightly greater decreases in IOP one year after surgery compared with cataract surgery alone. However, due to differences in the effects among the individual studies and potential for bias in the study results, this conclusion is not definitive. The effect between combined surgery and cataract surgery alone on the rate of complications was uncertain. No information was available for long-term outcomes (five or more years after surgery). Overall, the quality of the evidence was very low to low due to differences in study characteristics (e.g., type of glaucoma surgery) and poor reporting of outcomes from included studies. These factors may influence the treatment effects when comparing combined glaucoma and cataract surgery versus cataract surgery alone.
+Various manoeuvres are used to assist the passage of the baby through the birth canal by manipulating the fetal shoulders and increasing the functional size of the pelvis. These manoeuvres can also be used before the baby's head appears to prevent the fetal shoulders becoming trapped in the maternal pelvis (shoulder dystocia). In this review, the two studies involving 25 women were not large enough to show if manoeuvres such as manipulating the mother's pelvis can prevent instances of shoulder dystocia. Rates of birth injury did not appear to be affected by carrying out the manoeuvres early. Neither study addressed important maternal outcomes such as maternal injury, psychological outcomes and satisfaction with birth. Because shoulder dystocia is a rare occurrence, more studies involving larger groups of women are required to properly assess the benefits and adverse outcomes associated with such interventions.
+We have included 42 trials of acupuncture and acupressure compared to a control (sham/placebo, medication, Chinese herbs, no treatment or usual care) in a total of 4640 women of reproductive age with period pain. Twenty-two studies were undertaken in China. Eight studies were undertaken in Iran, four studies in Taiwan, two studies in Korea, and one each in Australia, Germany, Hong Kong, Thailand, Turkey, and the USA.The evidence is current to September 2015. There was insufficient evidence to demonstrate whether or not acupuncture or acupressure is effective in treating primary dysmenorrhoea, and for most comparisons no information was available on adverse events. The quality of the evidence was low or very low for all comparisons. The main limitations were risk of bias, poor reporting, inconsistency and risk of publication bias.
+In this review, the efficacy and safety of psychostimulants for amphetamine abuse or dependence were studied. We found eleven studies enrolling 791 amphetamine-dependent participants and assessing the effects of four different psychostimulants: dexamphetamine, bupropion, methylphenidate and modafinil. Psychosocial interventions were additionally provided to all participants. The studies were conducted in the USA, Australia or Northern Europe, and study length ranged from 8 to 20 weeks. Psychostimulants did not reduce amphetamine use or amphetamine craving and also did not increase sustained abstinence in comparison with placebo. Retention in treatment was similar and low with both treatments. Psychostimulants also did not increase the risk of adverse events that were intense enough to induce dropouts. Research with larger and longer trials is needed to determine whether psychostimulants can be a useful replacement therapy for patients with amphetamine abuse or dependence. The design of future trials should consider the level of dependence at study entry, the potency and the dose of the psychostimulant administered, the length of the trial and the representativeness of included participants.
+We included 27 randomised controlled trials (RCTs), which included 4031 women. The evidence is current to April 2016. There was low quality evidence for live birth and moderate for clinical pregnancy that fresh blastocyst stage transfer is associated with higher rates than fresh cleavage stage transfer. This suggests that if 29% of women achieve live birth after fresh cleavage stage transfer, between 32% and 42% would do so after fresh blastocyst stage transfer. There was no evidence of a difference between the groups in cumulative pregnancy rates (i.e. pregnancies from both fresh and thawed cycles deriving from a single egg collection procedure), but the evidence for this outcome was very low quality. Thus, although there is a benefit favouring blastocyst transfer in fresh cycles, it remains unclear whether the day of transfer impacts on cumulative rates of live birth and pregnancy. There was no evidence of a difference between the groups in multiple pregnancy and miscarriage rates, but the quality of evIdence was low. Future RCTs should report rates of live birth, cumulative live birth, and miscarriage to enable ART consumers and service providers to make well informed decisions on the best treatment option available. The evidence was of low quality for most outcomes. The main limitation was serious risk of bias, associated with failure to describe acceptable methods of randomisation, and unclear or high risk of attrition bias.
+All three included trials were randomised, but the blinding of intervention and outcome measurement varied. Data from two trials (enrolling 139 infants) were combined as they enrolled infants between 12 and 21 days of age, but data from one trial (enrolling 292 infants) were reported separately because researchers randomised infants aged less than 72 hours. The timing when the outcomes were measured varied among studies so it was not appropriate to combine some results. In one study all deaths that occurred were reported from the time babies were randomised not from when treatment started, hence there was a greater number of babies who died in that study. One study received grant support and the industry provided Aerochambers and metered dose inhalers of budesonide and placebo for the same study. No conflict of interest was identified. Evidence from two studies in 370 infants, who were randomised between 12 and 21 days of age and who contributed data to the primary outcome of this review, showed that inhaled steroids administered after 7 days of age compared with systemic steroids did not decrease the incidence of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age. Evidence from the single study in which infants were randomised at less than 72 hours of age did not show difference the incidence of death or BPD. Evidence from three studies in 431 infants contributing to secondary outcomes showed that inhaled steroids administered after seven days of age compared with systemic steroids did not significantly alter the incidence of BPD at 36 weeks' postmenstrual age, hyperglycaemia, hypertension, duration of ventilation, duration of oxygen supplementation, length of hospital stay, intraventricular haemorrhage grade III-IV, periventricular leukomalacia, necrotising enterocolitis, gastrointestinal bleed, retinopathy of prematurity stage > 3, culture-proven sepsis or the incidence of adverse effects. Adverse event profiles did not differ for inhaled versus systemic steroids but some potential complications of steroid treatment have not been reported. More research is needed to show whether any form of routine use of steroids results in overall health improvements for babies at risk of bronchopulmonary dysplasia. Evidence quality (according to GRADE criteria) was moderate to low.
+Our evidence is current to May 2015. We found three trials in total. Two trials recruited adults from the general population or from among hospital staff in Finland. These trials (total 253 adults) compared intranasal steroid sprays, which allow steroids to be puffed into the nostrils, to sprays containing placebo only. We found a third trial, which recruited 100 children referred to outpatient clinics in an Iranian paediatric hospital. This trial compared intranasal steroid spray to no spray and gave oral antibiotics to all participants. Neither of the two trials comparing steroid spray to placebo spray in adults showed a benefit of steroids across a range of different measures. The trial comparing steroid spray to no spray in children did find some evidence of benefit but we rated the quality of the evidence from this trial as very poor and the results were unclear. We could not combine the results of the trials to assess this question further. There were no reports of adverse events. The available evidence suggests that we should not use intranasal steroids for the common cold. However, as we found only three small trials, we cannot be sure that there is no effect without performing larger, well-designed trials.
+We found 16 studies that randomly assigned 26,795 patients 60 years or older with high blood pressure to antihypertensive drug therapy or to placebo or untreated control for a mean duration of 4.5 years. Blood pressure-lowering drug therapy in people with hypertension 60 years and older reduced death, strokes, and heart attacks. Benefit was similar if both upper and lower blood pressure numbers were elevated and if only the upper number was elevated. First-line treatment used in most studies was a thiazide. More patients withdrew from the studies owing to side effects of these drugs. The magnitude of benefit in cardiovascular mortality and morbidity observed was probably greater among 60- to 79-year-old patients than in very elderly patients 80 years or older. Blood pressure-lowering drug treatment for healthy persons (60 years or older) with raised blood pressure reduces death, heart attacks, and strokes. Review authors graded the quality of evidence as high for reduction in death and as moderate for reduction in stroke and heart attacks.
+The aim of this review was to evaluate the benefits and harms of drug treatments for preventing the complications of idiopathic hypercalciuria. We identified four studies comparing thiazides (diuretics) with either standard treatment of clinical follow-up and increased water intake or specific dietary recommendations and one study comparing thiazides plus a potassium salt. There was a decrease in the number of new stones in the group receiving thiazides as well as an increase in the time taken for new stone formation. The addition of potassium salts to thiazide treatment significantly reduced the amount of calcium excreted in the urine. No studies in children were identified and there were no studies investigating the use of drug treatment for those with hypercalciuria but were symptom free.
+Risk of death or heart attack following either treatment appeared the same, but this may be because too few trial participants were collected together in the review and variation between trials (heterogeneity) may be masking true differences. Further trials of new techniques in a greater variety of patients with subsequent systematic review are needed.
+The authors of the review identified eight randomised studies involving 2007 adult patients with a history of previous treatment failures in outpatient settings. The heroin users on the programs were requested to attend the clinic to receive and inject prescribed heroin from two to three times a day. Adverse events were consistently more frequent in the heroin groups. The trialists recommend that the treatment should be properly established so that necessary intensive care can be provided in an emergency. According with the current evidence, heroin prescription should be indicated to people who is currently or have previously failed maintenance treatment, and it should be provided in clinical settings where proper follow-up is ensured.
+A systematic review of benzodiazepine treatment of non-alcohol related delirium discovered very few trials (one randomized, controlled study of mechanically ventilated patients, and thus poorly reflective of delirious patients as a whole; and two partially controlled studies), the results of which indicate that at this time there is no evidence to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients.
+We included in this review three trials evaluating acute or subacute pain in patients with LBP (n = 197 participants). Most participants were middle-aged and were recruited from primary or tertiary care centres. Duration of treatment programmes ranged from four weeks to six weeks. MCE showed no benefit over spinal manipulative therapy, other forms of exercise or medical treatment for reducing pain or disability among patients with acute and subacute LBP. Whether MCE can prevent recurrences of LBP remains unclear. Results of this review include evidence of very low to moderate quality. We downgraded all comparisons for imprecision due to small study sample sizes.
+The prevalence of HCM in the general population, as determined from echocardiographic studies in the United States, Japan, and China, has ranged from 0.16 to 0.29 percent. Treatment options for HCM ranges from drugs to surgery with each having its own limitations. Active cardiac pacing was suggested as a treatment option in some trials. We conducted this review to assess the available evidence on the effects of active pacing in drug-refractory or drug-intolerant HCM patients. Five studies (reported in 10 papers) were found to be relevant. However, three of the five studies provided un-usable data. Thus data from only two studies (reported in seven papers) with 105 participants was included for this review. There was insufficient data to compare results on all-cause mortality, cost effectiveness, exercise capacity, Quality of life and Peak O2 consumption. There was no difference in exercise capacity when comparing active pacing versus placebo pacing. However left ventricular outflow tract obstruction decreased significantly in the active pacing group compared to placebo. New York Heart Association functional class increased in the active pacing group compared to the placebo group and this was also observed when comparing active pacing versus trancoronary ablation of septal hypertrophy. Interpretation of these data needs to be cautious because existing data is derived from small trials at high risk of bias, which concentrate on physiological measures. Their results are inconclusive. Further large and high quality trials with more appropriate outcomes are warranted.
+This review considers the effect of antileukotriene agents, (normally used as add-on preventer therapy in chronic asthma), when used during acute asthma treated in emergency settings. We identified eight randomised controlled trials (RCTs) on 1470 adults and 470 children addressing this question, and in most of these studies participants were also given courses of corticosteroids at the time of treatment. We did not find a significant difference in the likelihood of being admitted to hospital between people treated with oral antileukotrienes and placebo or usual care. There was no significant difference in participants requiring additional care (including hospital admission or other treatment options) at the end of the studies between treatment and control groups. There was an improvement in lung function in people taking antileukotrienes compared to those on placebo. More research in this area is required, and the low number of studies recruiting children does not enable us to provide evidence on what effects this class of drugs has in children. There were two trials that randomised 772 adults and 276 children to receive intravenous antileukotrienes and there was no statistically significant difference in hospital admissions, however there was an improvement in lung function in adults on antileukotrienes.
+We found 14 randomised controlled trials with a total of 2165 participants. Most were not commercially funded. Key findings: Double versus repeated single embryo transfer Based on low quality evidence, there was no indication that overall live birth rates differed substantially when repeated single embryo transfer (either two cycles of single embryo transfer or one cycle of single embryo transfer followed by transfer of a single frozen embryo in a natural or hormone-stimulated cycle) was compared with double embryo transfer. The evidence suggested that for a woman with a 42% chance of live birth following a single cycle of double embryo transfer, the chance following repeated single embryo transfer would be between 31% and 44%. The risk of multiple birth was very much lower in the single embryo transfer group: for a woman with a 13% risk of multiple pregnancy following a single cycle of double embryo transfer, the estimated risk following a repeated single transfer was between 0% and 2%. Double versus single embryo transfer We found high quality evidence that the chances of live birth were lower after one cycle of fresh single embryo transfer than after one cycle of fresh double embryo transfer. For a woman with a 45% chance of live birth following a single cycle of double embryo transfer, the chance following a single cycle of single embryo transfer was between 24% and 33%. However, the risk of twins was about seven times higher after double embryo transfer. Conclusion: Repeated single embryo transfer appears the best option for most women undergoing ART. Most of the evidence currently available concerns younger women with a good prognosis.
+We included 33 randomised clinical trials comparing L-ornithine L-aspartate with inactive placebo or no intervention and six randomised clinical trials comparing L-ornithine L-aspartate with other anti-encephalopathy treatments; some trials included more than one comparison. Five of the included trials tested L-ornithine L-aspartate for the prevention of hepatic encephalopathy while 30 trials tested its use as treatment for people with acute, chronic, or minimal hepatic encephalopathy. The length of treatment varied from three to 35 days in the trials testing the intravenous preparation (average eight days) and from seven to 180 days in those testing the oral preparation (average 30 days). Our analyses showed L-ornithine L-aspartate might reduce deaths, improve hepatic encephalopathy, and prevent serious side effects compared with placebo or no treatment, but that it had no additional beneficial effects when compared with other medicines used to prevent and treat this condition. The evidence we found was very weak, and so we are not confident that L-ornithine L-aspartate is of use for preventing or treating hepatic encephalopathy in people with cirrhosis. Many studies were unpublished and so had not been carefully vetted, and many of the published trials received support from the pharmaceutical industry which introduces an element of bias. Accordingly, more information is needed before the value of L-ornithine L-aspartate for preventing and treating hepatic encephalopathy can be determined.
+Only three randomised controlled trials, with a total of 130 participants met the review requirements and provided useable data. The quality of evidence available was low, no real difference was noted between chlorpromazine and penfluridol for hospital admissions, incidence of akathisia or numbers of participants leaving the study early. There were no deaths during the trials. We were unable to use the available data for global and mental state due to poor reporting, and no studies reported relapse data. We can not make firm conclusions regarding the comparable effectiveness between chlorpromazine and penfluridol with such poor quality data - but penfluridol only needs to be given once per week - which could help the poor adherence to medication common with schizophrenia. Remarkably, for such old drugs, more trials that report high-quality data are needed.
+The review authors searched the literature for treatment studies of apathy, or a component of apathy, in people who have had a traumatic brain injury. One randomised controlled trial was found which examined the use of cranial electrotherapy stimulation for inertia, which is a component of apathy. Evidence for the effectiveness of this treatment is particularly restricted by the small number of participants and the lack of statistical analyses to demonstrate that the cranial electrotherapy stimulation treatment was more successful than sham or no treatment. More methodologically rigorous studies need to be conducted to investigate different methods of effectively treating apathy in people with traumatic brain injury.
+We included six trials (involving 800 women) in this review. We found that the application of a skin preparation to the areas affected by stretch marks during pregnancy did not prevent the development of stretch marks in the women during pregnancy. Only three trials (involving 461 women) looked at the severity of the stretch marks and did not show a clear difference. The preparations used included Alphastria, Trofolastin, Verum, olive oil and cocoa butter, which all contain vitamin E; Alphastria and Verum also have hyaluronic acid. Of the six trials, we judged three to be at low risk of bias. All trials were relatively small, with four of the six trials each including less than 100 women. The trials were also different in terms of when the women first started to use the topical applications, ranging from the first trimester to the first 20 weeks.
+We searched the literature until April 2019 for RCTs that compared early enteral nutrition with delayed enteral nutrition, with or without SPN, in adults in an ICU. RCTs, if designed and conducted properly, represent the highest methodological standard in clinical research. We included seven RCTs with 345 participants. Participants were admitted to the ICU for more than 72 hours with medical, surgical, or trauma diagnoses. Six trials with 318 participants compared early enteral nutrition with delayed enteral nutrition. One trial with 27 participants compared early enteral nutrition with SPN versus delayed enteral nutrition with SPN. Overall, results showed no clear differences in the number of deaths within 30 days (one study, 38 participants), intolerance to feeding (one study, 59 participants), or development of pneumonia (four studies, 192 participants), between those who received early enteral nutrition or delayed enteral nutrition. We assessed the evidence as very low-quality, meaning the findings could potentially change with additional studies. In the one small trial that also gave SPN, the number of deaths, people with infectious complications, and the duration of mechanical ventilation were not clearly different between those who received early enteral nutrition or delayed enteral nutrition (very low-quality evidence). Future trials should continue to look into the impact of early enteral nutrition, with or without SPN, on important clinical outcomes in adults hospitalized in ICUs. We assessed the quality of the evidence as very low, meaning we were uncertain about the findings, as included studies were small, and provided an unclear description of the methods that they used. Participants in the studies had different causes for their critical illness. The outcomes were not always measured in the same way or at the same time in the different trials; some trials did not report on them.
+The reviewers conclude that the benefit of light treatment is modest though promising for non-seasonal depression. The short-term treatment as well as light administered in the morning and with concomitant sleep deprivation in sleep deprivation responders appear to be most beneficial for treatment response. Hypomania as a potential adverse effect needs to be considered. Due to limited data and heterogeneity of studies these results need to be interpreted with caution.
+Five randomized trials are included in this review. These studies were published between 1988 and 2000 and included a total of 431 preterm and low birth weight infants. Indomethacin was given intravenously in four trials and orally in one, in total amounts of 0.6 to 1.6 mg/kg for the prolonged course (six to eight doses) and 0.3 to 0.6 mg/kg for the short course (two to three doses). There was no significant benefit of prolonged indomethacin administration on failure of the PDA to close after completion of allocated treatment (four studies, 361 infants). Prolonged course of indomethacin compared to the short course did not reduce the rate of PDA re-opening after initial closure (three studies, 322 infants), rate of PDA re-treatment (five studies, 431 infants), or ligation rate (four studies, 310 infants). The prolonged course was associated with decreased incidence of renal function impairment (three studies, 318 infants). However, a prolonged indomethacin course increased the risk of NEC (four studies, 310 infants). The number of deaths was no different.
+This systematic review was undertaken to help inform the 2013 WHO guidelines which aimed to revise the recommendations of when to start therapy in 2 to 5 years old children. The authors identified two randomised controlled trials (RCTs) that compared immediate with deferred initiation of cART in HIV-positive children aged 1 to 12 years in Thailand or Cambodia. Additional analyses of 122 children enrolled in the two studies at ages 2 to 5 years were made available for this review. A cohort study from South Africa in HIV-positive children (median age 3.5 years) starting tuberculosis treatment and ART was also included. Results showed that we still lack enough evidence to determine whether early or late initiation of cART is best in children aged 2 to 5 years. The authors recognized the lack of evidence but highlighted the potential value of simplifying WHO recommendations to start cART in all children below five years with the goal of providing programmatic advantage to treatment programmes in resource-limited settings.
+However, the review found there is not enough evidence from trials to show whether beta-blockers are safe and effective for tremor in Parkinson's disease. The blood pressure lowering effect of beta-blockers may be a problem to people with Parkinson's disease and normal blood pressure.
+We analysed data from 33 studies of CT that included a total of approximately 2000 participants and were conducted in 12 countries. We found that, compared with receiving usual treatment or engaging in non-specific activities, people completing CT may show some benefits in overall cognition, as well as in more specific cognitive abilities such as verbal fluency, and that improvements may last for at least a few months. We did not find any evidence that participating in CT was associated with increased burden for participants. However, we also found no evidence that CT was better than participating in other active treatments. The quality of the studies we reviewed varied but overall was not very high, so our certainty in some of these findings is low. Future studies should continue improving on quality, should continue comparing CT with other treatments, and should follow participants for a longer period to understand whether observed benefits for cognition last beyond the short or medium term.
+In total, we included five randomised controlled trials involving 297 women. Three trials assessed imiquimod compared with placebo, one trial assessed imiquimod compared with cidofovir, and one compared two different doses of indole-3-carbinol. We pooled data from the three similar trials involving 104 women and found imiquimod to be more effective in clearing high-grade VIN lesions by six months than placebo. Most studies did not include longer term follow-up, but findings from one study suggested that women in whom VIN was completely cleared at six months were likely to sustain this response by 12 months. This single study showed no difference in rates of progression to cancer between study groups. We are uncertain about these longer-term findings and would like them to be corroborated by other trials. We found limited evidence on side-effects. However, evidence from one study found that side-effects, such as pain and itching of the skin over the vulva, occurred more frequently among women in the imiquimod group compared with the placebo group, and were usually managed by reducing the frequency of applications. The trial comparing imiquimod with cidofovir involved 180 women. These topical treatments appeared to be similarly effective at six months. However, there were no longer term results available for this trial. The trial of indole-3-carbinol was a small trial of only 13 women that compared two different doses of the medication and we could not draw any conclusions about this treatment. We found no evidence on the effectiveness of other treatments, such as HPV vaccines to treat high-grade VIN; however, we identified five ongoing trials that may provide important evidence in the future. Imiquimod appears to be effective and reasonably safe for the treatment of VIN, and cidofovir shows considerable promise, but more research is needed. In particular, more evidence is needed on longer term effectiveness of both treatments, and on the risk of VIN progressing to vulval cancer after treatment.
+This review assessed the effects of cultural competence education for health professionals. Five studies were included involving 337 health professionals (including general practitioners, primary care teams and counsellors) and 8400 patients. Three studies were conducted in the USA, one in Canada and one in The Netherlands. At least 3000 patients were from culturally and linguistically diverse (CALD) backgrounds and some of the health professional groups were also from CALD backgrounds. Due to differences in terminology and their cultural meanings, and the evolving nature of concepts and practices in this area, in this review we use the term 'CALD participants' when referring to minority, CALD populations as a whole. When referring to participants in included studies we describe them in the terms used by the relevant study authors. The studies differed in how the education was provided and which outcome measures were used. Involvement in care improved in one study in The Netherlands measuring mutual understanding between minority CALD background patients and their doctors. Health behaviour also changed in one small study in the USA, in which women whose counsellors had received education were three times more likely to attend planned counselling sessions. However there was no evidence of an effect on a range of treatment outcomes or evaluations of care. None of the five included studies examined the effect of cultural competence education on healthcare organisations, or assessed adverse outcomes. The review findings showed some support for cultural competence education for health professionals. These findings are tentative, however, as the quality of the evidence was low and more data are needed. Future research on cultural competence education for health professionals should seek greater consensus on the core components of cultural competence education, how participants are described and the outcomes assessed.
+This review included thirteen randomized controlled trials comparing abstinence-only programs to various control groups (e.g., "usual care," no intervention). Although we conducted an extensive international search for trials, all included studies enrolled youth in the US (total baseline enrollment=15,940 participants). Programs were conducted in schools, community centers, and family homes; all were delivered in family units or groups of young people. We could not conduct a meta-analysis because of missing data and variation in program designs. However, findings from the individual trials were remarkably consistent. Overall, the trials did not indicate that abstinence-only programs can reduce HIV risk as indicated by behavioral outcomes (e.g., unprotected vaginal sex) or biological outcomes (e.g., sexually transmitted infection). Instead, the programs consistently had no effect on participants' incidence of unprotected vaginal sex, frequency of vaginal sex, number of sex partners, sexual initiation, or condom use. One trial favored an abstinence-only program over usual care for incidence of vaginal sex (n=839), but this was limited to two-month follow-up and was offset by measurement error and six other studies with non-significant effects (n=2615). One evaluation found several significant adverse (harmful) program effects: abstinence-only program participants were more likely than usual-care controls to report sexually transmitted infections (n=2711), pregnancy (n=1548), and increased frequency of vaginal sex (n=338). These effects were offset by high attrition and other studies showing non-significant effects. We concluded that abstinence-only programs do not appear to reduce or exacerbate HIV risk among participants in high-income countries, although this evidence might not apply beyond US youth. Trial limitations included underreporting of relevant outcomes, reliance on program participants to report their behaviors accurately, and methodological weaknesses in the trials.
+We included six studies with 326 participants who undertook therapeutic exercises before, during and/or after HNC treatment. We could not combine the results of the studies because of the variation in participants' cancers, their treatments, the outcomes measured and the tools used to assess them, as well as the differing time points for testing. Researchers have compared: (i) therapeutic exercises versus treatment as usual (TAU); (ii) therapeutic exercises versus sham therapy; (iii) therapeutic exercises plus TAU versus TAU. The therapeutic exercises varied in their design, timing and intensity. TAU involved managing patients' dysphagia when it occurred, including inserting a tube for non-oral feeding. The evidence is up to date to 1 July 2016. We found no evidence that therapeutic exercises were better than TAU, or any other treatment, in improving the safety and efficiency of oral swallowing (our primary outcome) or in improving any of the secondary outcomes. However, there is insufficient evidence to draw any clear conclusion about the effects of undertaking therapeutic exercises before during and/or immediately after HNC treatment on preventing or reducing dysphagia. Studies had small participant numbers, used complex interventions and varied in the choice of outcomes measured, making it difficult to draw reliable conclusions. There were no reported adverse events directly attributable to the intervention (swallowing exercises). The current quality of the evidence to support the use of therapeutic exercises before, during and/or immediately after HNC treatment to prevent/reduce dysphagia is very low. We need better designed, rigorous studies with larger participant numbers and agreed endpoints and outcome measurements in order to draw clear(er) conclusions.