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GEM benchmark 92

[ "Five studies involving 187 females with an age range of 15 to 40 years were included in this review. Oral isoxsuprine was examined in two studies; terbutaline oral spray, ritodrine chloride and oral hydroxyphenyl-orciprenalin were compared with placebo in a further three studies. All of the studies were conducted over 30 years ago and none were of high quality. None of these medications, other than isoxsuprine combined with acetaminophen and caffeine, were reported to have any beneficial effect. Side effects with these medications were reported in up to a quarter of the participants and included nausea, vomiting, dizziness, quivering, tremor and palpitations. At present there is insufficient evidence to allow confident decision-making about the use of beta2-adrenoceptor agonists for dysmenorrhoea." ]

[ "As only randomised controlled trials (RCTs) comparing groups with and without a weight-reducing diet can answer these issues, we only included RCTs in our systematic review. Thirty articles reporting on eight studies met the inclusion criteria. The 8 included studies involved a total of 2100 participants with high blood pressure and a mean age of 45 to 66 years. Mean treatment duration was 6 to 36 months, and there was little or no information about deaths or other long-term complications. Three of eight studies provided effects on systolic and diastolic blood pressure, suggesting that weight loss interventions reduced systolic and diastolic blood pressure by 4.5 mm Hg and 3.2 mm Hg, respectively. Five out of eight studies reported body weight; weight loss interventions reduced weight by 4.0 kg as compared to controls. No useful information on adverse effects was reported in the included trials. In conclusion, we found no evidence for effects of weight loss diets on death or long-term complications and adverse events. Results on blood pressure and body weight should be considered uncertain, because not all studies were included in the analyses." ]

[ "We looked for randomised controlled trials in people with recent onset of stroke symptoms that compared LMWH or heparinoids with UFH. We found nine trials involving 3137 participants; overall these trials had a moderate risk of bias (this means that the results are likely to be less credible than if the risk of bias was low). No new trials were included in this updated review. None of the studies reported reliable information on disability or recovery after stroke. Compared with UFH, there was no evidence of an effect of LMWH or heparinoids on death from all causes during the treatment period (quality of the evidence was low). Although LMWH or heparinoid were associated with significantly fewer clots in leg veins (DVT) than UFH, the number of major events such as when a blood clot becomes lodged in an artery in the lung (pulmonary embolism) and bleeding inside the skull (intracranial haemorrhages) was too small to know whether the harms outweighed the benefits. For people with ischaemic stroke who need immediate treatment with anticoagulants, evidence from the included clinical trials did not provide reliable evidence on the balance of risk and benefit for each type of heparin. Additional large scale research would be needed to resolve this uncertainty. Overall, there was a moderate risk of bias in the included studies. Using GRADE criteria we found that evidence quality was low overall." ]

[ "Results from this systematic review show that ART soon after birth is preferable to delaying treatment, because infants are less likely to die or become sick. Starting a first-line treatment regimen that includes lopinavir/ritonavir rather than nevirapine is preferable, because infants and young children are less likely to have to stop treatment, whether or not they had previously been exposed to nevirapine. However, lopinavir/ritonavir is more expensive than nevirapine. It is also currently only available as an inconvenient liquid, which tastes bitter and has to be refrigerated, making it challenging to implement in all parts of the world. While waiting for better formulations to become available, it may be possible to switch from lopinavir/ritonavir to nevirapine once the HIV virus levels become undetectable. However, based on the evidence currently available, a viral load test would be required to identify those children who could safely substitute lopinavir/ritonavir with nevirapine. Viral loads are expensive and not widely available in most countries in sub-Saharan Africa. An alternative treatment approach is to give a stronger drug combination (four different drugs together) when treatment is first started, then reduce down to three drugs after a short while. However, this strategy did not appear to have long-term benefits. A 'treatment interruption' strategy, in which infants start ART soon after birth but then stop medication after 1-2 years, is difficult to implement. Children stopping ART need to restart it very quickly to prevent them becoming sick, and monitoring a child off treatment is challenging in settings with few resources." ]

[ "We found 18 studies including a total of 2268 people: 12 included adults, five included children and one included individuals from both age groups. Most people included in the studies had mild to moderate persistent asthma, and studies generally lasted between three and 12 months. People in the intervention group were given one of a variety of technologies to record and share their symptoms (text messaging, Web systems or phone calls) and were compared with a group of people who received usual care, or a control group. We could not tell whether people in the telemonitoring groups had a higher or lower chance than people in the control group of having attacks that would require a course of oral steroids, a visit to the emergency department or a hospital stay. No reports described other potential harms of home telemonitoring. Studies used lots of different types of technology, and we couldn't tell whether some were better than others. Our confidence in the results ranged from moderate to very low, meaning that additional studies are likely to change some of these results and may influence how much we believe them. Using technology to monitor people with asthma from home may offer benefits over usual care for overall quality of life, but the effect was small, and studies did not agree with each other. These interventions may provide benefits for lung function, but lots of people dropped out of the studies, so we couldn't be sure." ]

[ "We included 29 randomised controlled trials in the review (3227 participants). Of these, results of 18 trials were pooled (2740 participants). Results from the remaining 11 trials could not be used in the meta-analysis because investigators did not use a way of measuring adhesions that would allow findings to be pooled with other data, or because important statistical information was not reported. We searched all evidence up to April 2014. Only one study evaluated pelvic pain and provided no evidence that the adhesion prevention agent made a difference. No evidence suggests that any of the investigated agents affected live birth rate. Regarding adhesions, participants given a fluid agent during surgery were less likely to form adhesions than participants who did not receive a fluid agent. When fluids and gels were compared with each other, gels appeared to perform better than fluids. No pharmacological agents showed good evidence of causing a significant effect on adhesions. No studies looked at differences in quality of life. All studies apart from one stated that investigators were going to assess serious adverse outcomes associated with the agents, and no adverse effects were reported. For gels, results suggest that for a woman with a 77% risk of developing adhesions without treatment, the risk of developing adhesions after a gel is used would be between 26% and 65%. For a woman with an 83% risk of worsening of adhesions after no treatment at initial surgery, the chance when a gel is used would be between 16% and 73%. Similarly, for hydroflotation fluids in a woman with an 84% chance of developing adhesions with no treatment, the risk of developing adhesions when hydroflotation fluid is used would be between 53% and 73%. Fluids and gels appear to be effective in reducing adhesions, but more information is needed to determine whether this affects pelvic pain, live birth rate, quality of life and long-term complications such as bowel obstruction. Further large, high-quality studies should be conducted in which investigators use the standard way of measuring adhesions as developed by the American Fertility Society (the modified AFS score). The quality of the evidence ranged from low to high. The main reasons for downgrading of evidence were imprecision (small sample sizes and wide confidence intervals) and poor reporting of study methods." ]

[ "We identified 17 studies which compared premedication with a placebo prior to day case surgery. Twelve studies involved benzodiazepines (sedatives), two involved opioids (painkillers), two involved beta-blockers, one compared a benzodiazepine with a beta-blocker and one involved a herbal medication. In general, the studies were of poor quality and many used anaesthetic techniques which are no longer common. Only seven studies directly measured time to ambulation or discharge and found that this was not affected by the use of premedication. Some studies used specific tests to assess for residual effects of the premedication. Although these were often impaired after surgery, this did not appear to delay discharge." ]

[ "We included 129 studies published up to August 2013 which examined 18,086 people. Participants included men and women of any age, although most were between 18 to 70 years old. There was considerable variation in the reporting quality of the studies. A quarter were partially funded by pharmaceutical companies, and it was unclear what impact this may have had on reporting of the results. Most studies appeared to be conducted within dermatology outpatient clinics. A range of treatments were evaluated, mostly in single studies. Most treatments were applied once or twice daily for between two and four weeks. Mycological cure (disappearance of fungal infection); and clinical cure (absence of symptoms such as redness and itchiness); were assessed in the majority of studies, along with side effects. Less than half of the studies assessed disease recurrence and hardly any assessed the time to achieve clinical cure, or whether study participants considered they had been cured. Almost all treatments were effective at achieving both mycological and clinical cure, compared with placebo. We combined data for several outcomes in two individual treatments: terbinafine against placebo and naftifine against placebo. Both were shown to be effective treatments. We combined data on different groups of treatments. There was no difference in rate of mycological cure between azoles and benzylamines. Combinations of antifungal treatment with a topical corticosteroid achieved higher clinical cure rates, probably because the skin redness disappears sooner due to the effect of the corticosteroid. There was no evidence of any difference in the speed of resolution of fungal infection with these combination treatments. The overall quality of the evidence for the different outcomes was rated as low to very low. There is currently insufficient evidence to be able to decide if one particular treatment is better than any of the others. All the treatments we evaluated reported low rates of mild side effects. This review highlights the need for better quality studies on treatments for fungal skin infections. Despite the limitations of our main findings, it appears that most active treatments are effective and further research should concentrate on comparing active treatments, rather than comparisons with a placebo. Topical treatments that need to be used only once a day over a short period of time may be more appealing in practice. Some of the treatments examined in our review may not be readily available in-low income countries." ]

[ "This review looked at the effect of cutting down the proportion of energy from fat in our food on body weight and fatness in both adults and children who are not aiming to lose weight. The review found that cutting down on the proportion of fat in our food leads to a small but noticeable decrease in body weight, body mass index and waist circumference. This effect was found both in adults and children. The effect did not change over time." ]

[ "This review looked at studies of iodised salt in the diet that included a comparison group. Six studies, most of them in children but some also in adults, were included. Iodine in the urine increased in all but one studies, but there was some concern that small children did not eat enough salt to achieve adequate iodine status. Some studies, but not all, also showed a reduction in the enlargement of the thyroid gland (goitre) that can accompany lack of iodine in the diet. Adverse effects were not reported, but these may not have been studied adequately. More high quality long term studies measuring outcomes related to child development, to deaths associated with iodine-deficiency and to adverse effects are needed." ]

[ "We found 26 studies including a total of 7654 adults with cancer. Most studies included both males and females. With regard to cancer type, most studies included people with a specific type of cancer, but some included a variety of cancer types. Furthermore, the type of screening differed: half of the studies asked participants to self-complete a screening questionnaire about their psychosocial health, while in the remaining studies screening interviews were conducted in which a healthcare professional questioned participants about their well-being face-to-face. Several studies showed benefits of screening on psychosocial well-being of cancer patients, such as their health-related quality of life, distress, care needs, and patient satisfaction. However, some studies also found negative effects. There were important differences between the studies: they assessed different psychosocial aspects (e.g. health-related quality of life, distress, care needs, and patient satisfaction) and differed in their modes of screening (i.e. self-report screening questionnaire versus screening interview), timing and frequency of the screening (1 to 12 times), outcome measures, and outcome time points. Due to these differences, only three studies studying the same intervention could be included in the analysis. Our results do not support the screening of psychosocial well-being and care needs in people with cancer. The certainty of the evidence was low, which means that we are uncertain about the results of the review due to variations in characteristics, and results of the studies and study designs." ]

[ "This review identified eleven randomised controlled trials that compared antidepressants with a placebo in people with schizophrenia who also had depression. There was some evidence that antidepressants did lead to an improvement in global outcome, but the small number of studies providing usable data and their poor quality, suggest that this evidence should be interpreted with caution. At present, there is no convincing evidence either to support or refute the use of antidepressants in treating depression in people with schizophrenia. Further well-designed, conducted and reported research is needed in this area." ]

[ "We included six randomised controlled trials that enrolled a total of 561 people. The trials were conducted in Germany (three trials), Iran, India, and China. In people with high-risk keratoplasty, one study compared systemic MMF with placebo, one study compared systemic MMF with systemic CsA, and one study compared CsA eye drops versus placebo. In people with normal-risk keratoplasty, one study compared tacrolimus eye drops to steroid eye drops, and two studies compared CsA eye drops to placebo in people experiencing rejection after keratoplasty. All studies reported clear graft survival, incidence of graft rejection, and adverse effects. We are uncertain as to the effects of immunosuppressants in the prevention of graft failure and rejection after high- and normal-risk keratoplasty, as the number of trials is limited, and, in general, the trials are small and at risk of bias. Future trials should be large enough to detect important clinical effects, conducted with a view to minimising the risk of bias, and they should measure outcomes important to patients. Three of the studies were supported by the pharmaceutical industry. We judged the quality of the evidence to be low to moderate. There was risk of bias in the included studies; the results were sometimes imprecise because of the small number of studies and small number of people enrolled in these studies; and in some analyses the results of individual trials were inconsistent." ]

[ "The reviewers identified 10 trials assessing the effect of tamoxifen on survival, quality of life, tumour size, and treatment side effects in advanced hepatocellular carcinoma. Tamoxifen had no significant effect on survival or tumour size. Tamoxifen did not improve quality of life." ]

[ "This review found 69 studies that evaluated educational outreach visits. Educational outreach visits appear to improve the care delivered to patients. When trying to change how health care professionals prescribe medications, outreach visits consistently provide small changes in prescribing, which might be potentially important when hundreds of patients are affected. For other types of professional practice, such as providing screening tests, outreach visits provide small to moderate changes in practice. But the effects really varied and why it varied could not be explained." ]

[ "Women who received chemotherapy after surgery (starting within eight weeks of surgery) survived approximately 25% longer than those receiving radiotherapy after surgery. Assuming that 60% of women with stage III endometrial cancer usually survive at least five years after surgery and radiotherapy, this would increase to 75% if they receive surgery and chemotherapy instead, depending on other risk factors, such as age. The risk of death which might have been caused by treatment was low with both chemotherapy and radiotherapy but we could not be sure if one was more harmful than the other. Chemotherapy may be associated with more side-effects (low blood counts, nerve damage and hair loss) compared with radiotherapy. In the trial that compared two different chemotherapy treatments, there was no clear evidence that using three anti-cancer drugs was better than using two. However, the final overall survival results of this trial have not yet been reported. Severe side-effects were much more common in women treated with three anti-cancer drugs than two drugs. Chemotherapy appears to be more effective than radiotherapy after surgery for women with stage III and IV endometrial cancer but may cause more side-effects. More research is needed to determine whether the addition of radiotherapy to chemotherapy improves outcomes and which anti-cancer drugs are best." ]

[ "In this review we included two randomised trials comparing planned caesarean versus planned vaginal birth for twin pregnancies which together included 2864 women. For important outcomes the evidence was assessed as being of moderate quality. For maternal mortality no events were reported in one trial and two deaths (one in each group) in the other. There was no clear evidence of differences between women randomised to planned caesarean or planned vaginal birth for death or serous illness in either the mothers or babies. No studies reported childhood disability. The number of women undergoing caesarean section was reported in both trials. Most women in the planned caesarean group had treatment as planned (90.9%), whereas in the planned vaginal birth group 42.9% had caesarean section for at least one twin. There were no significant differences between groups for failure to breastfeed or for postnatal depression. There is very little clear research evidence to provide guidance on the method of birth for twin pregnancies. The benefits and risks should be made available to women, including short-term and long-term consequences for both mother and babies. Future research should aim to provide more clarity on this issue as medical interventions in the birth process should be avoided unless there is reasonable clinical certainty that they will be of long-term benefit." ]

[ "In this review of randomised controlled studies, we evaluated the effects of adding marine omega-3 fatty acids to women’s diets during pregnancy or lactation on allergic diseases in their children. We analysed eight trials that involved 3366 women and 3175 children. The women were randomly assigned to receive a marine omega-3 supplement (as fish oil capsules, or added to foods) or no treatment during pregnancy (five trials), during breast feeding (two trials) or both pregnancy and breast feeding (one trial). Overall, the methodological quality of the trials varied, with only two trials being at low risk of bias. Overall, the results showed little effect of maternal marine omega-3 supplementation during pregnancy and/or breast feeding for the reduction of allergic disease in the children. However there were reductions in some outcomes such as food allergy during the baby's first year and eczema with marine omega-3 supplementation in women with a baby at high risk of allergy. Currently, there is not enough evidence to say that omega-3 supplements from marine origin during pregnancy and/or breast feeding for mothers will reduce allergies in their children. In terms of safety for the mother and child, omega-3 fatty acids supplementation from marine origin during pregnancy did not show increased risk of excessive bleeding after the baby was born (postpartum haemorrhage) or early childhood infections." ]

[ "The last search for trials was in February 2018. We assessed the evidence from 14 randomised controlled trials comparing lamotrigine with carbamazepine. We were able to combine information for 2572 people from nine of the 14 trials; for the remaining 1215 people from five trials, information was not available to use in this review. Results The results of the review suggest that people are more likely to withdraw earlier from carbamazepine than lamotrigine treatment. The most common medicine-related reason for withdrawal was side effects: 52% of total withdrawals in participants on carbamazepine and 36% of total withdrawals in participants on lamotrigine. The second most common medicine-related cause for withdrawal was seizure recurrence: 58 of 719 total withdrawals (8%) on carbamazepine and 105 of 697 total withdrawals (15%) on lamotrigine. The results suggest that recurrence of seizures after starting treatment with lamotrigine may happen earlier than treatment with carbamazepine. They also suggest that freedom from seizures for a period of six months may occur earlier on carbamazepine than lamotrigine. The majority of the people included in the 14 trials (88%) experienced focal seizures, so the results of this review apply mainly to people with this seizure type. The most common side effects reported by participants during the trials were dizziness, fatigue, gastrointestinal problems, headaches and skin problems. These side effects were reported a similar number of times by people taking lamotrigine or carbamazepine. Quality of the evidence For people with focal onset seizures, we judged the quality of the evidence to be high for the outcomes of seizure recurrence and remission of seizures and we judged the quality of the evidence to be moderate for the outcome of treatment failure. The design of the trials (specifically, whether the people and treating clinicians knew which medication they were taking) may have influenced the rates of withdrawal from treatments. Up to 50% of people in the trials used in our results may have been wrongly classified as having generalised seizures; for people with generalised onset seizures, we judged the quality of the evidence to be moderate for the outcomes of seizure recurrence and remission of seizures and low quality for the outcome of treatment failure. Conclusions For people with focal onset seizures, lamotrigine and carbamazepine are effective treatments and a choice between these two treatments must be made carefully. More information is needed for people with generalised onset seizures. 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." ]

[ "In most cases, efforts to regulate health worker migration have not been properly evaluated. The review authors found only one study that met their stated requirements for types of study designs. This study looked at the impact of United States (US) immigration law on the number of nurses emigrating from the Philippines to the USA. US government immigration laws were changed in the 1960s, giving equal access to European and non-European immigrants. The study measured the number of nurses migrating from the Philippines to the USA in the years before and after the law had changed. The study showed that: - The change in US immigration laws probably increased the number of nurses migrating from the Philippines to the USA. The quality of this evidence is moderate. The review shows that there is a huge gap in our knowledge about the effectiveness of policy interventions that attempt to regulate the movement of health professionals from low- and middle-income countries." ]

[ "Randomised trials have compared transjugular intrahepatic portosystemic stent-shunts with paracentesis. Mortality, gastrointestinal bleeding, renal failure, or infection did not differ significantly between the two intervention groups. Transjugular intrahepatic portosystemic stent-shunts effectively decreased the risk of ascites fluid re-accumulation, but was associated with an increased risk of hepatic encephalopathy." ]

[ "This review identified four studies that compared these drugs with placebo. Over the first 2 hours of treatment there was no evidence that patients improved in terms of lung function, although a possible late benefit was detected. The studies do not give a clear indication of whether there was benefit in terms of reduced symptoms or hospital admissions, but side effects were found to be more common with methylxanthines. We conclude that, given current evidence, methylxanthines should not be used for acute exacerbations of chronic obstructive pulmonary disease." ]

[ "We included one study (enrolling 70 newborn infants) that compared needle aspiration followed by immediate removal to chest tube placement for the treatment of pneumothorax and one study (72 newborn infants) that compared needle aspiration with the angiocatheter left in situ to chest tube placement for the treatment of pneumothorax. Evidence is up to date as of June 2018. The use of needle aspiration compared to chest tube placement did not reduce mortality or any complications related to the procedure. About 30% of the infants with pneumothorax who were treated with needle aspiration followed by immediate removal never required the placement of an intercostal tube; none of the infants with pneumothorax who were treated with needle aspiration left in situ required the placement of an intercostal tube. However multiple factors might explain this finding. The two small trials identified do not provide sufficient information to determine which of the two techniques is better to treat pneumothorax in neonates. However it seems that needle aspiration might reduce the need for an intercostal tube in a relevant proportion of newborn infants." ]

[ "Eight of the trials looked at email compared with standard methods of communication. Where email was compared to standard methods of communication we found that we could not properly determine what effect email was having on patient/caregiver outcomes, as there were missing data and the results of the different studies varied. For health service use outcomes the situation was the same, but some results seemed to show that an email intervention may lead to an increased number of emails and telephone calls being received by healthcare professionals. One of the trials looked at email counselling compared with telephone counselling. We found that it only looked at patient outcomes, and found few differences between groups. Where there were differences these showed that telephone counselling leads to greater changes in lifestyle than email counselling. None of the trials measured how email affects healthcare professionals and only one measured whether email can cause harm. All of the trials were biased in some way and when we measured the quality of all of the results we found them to be of low or very low quality. As a result the results of this review should be viewed with caution. The nature of the results means that we cannot make any recommendations for how email might best be used in clinical practice. Future research should make allowances for how quickly technology changes, and should consider how much email would cost to introduce and what effect it has on the use of healthcare resources. Research reports should be sure to clearly report their methods and findings, and researchers interested in carrying out research in this area should be assisted in developing ideas and put them into action." ]

[ "We included five small trials that randomised only 234 people, almost all with stroke. Two trials investigated dysarthria treatment versus an attention control and three compared one treatment with usual care. There were no trials that compared one treatment to no treatment. We found few randomised controlled trials of dysarthria treatment, and those that have been conducted involved small numbers of participants, or were not adequately designed or had serious reporting flaws. We compared many different measures at various time points after treatment, so caution is recommended when interpreting results. We found no evidence of effectiveness on most measures, including long-lasting improvement in every day communication abilities. A positive finding was short-term improvement in muscle movement, such as tongue and lip control. However, this result is not reliable because it was based on small numbers of people, and we found concerns about the conduct and reporting of some trials. This finding needs to be investigated in a bigger, better designed trial. We found insufficient evidence to tell us whether any one treatment is better than any other or whether treatment is better than general support, or no treatment. We found no studies that examined timing, duration, or intensity of treatment. This is a clinically important question and should be considered in future trials. The included trials varied in quality but all included small numbers of participants. Overall, studies were rated as low to very low quality evidence." ]

[ "This review assesses the various forms of medication used to treat the condition. Nineteen randomised controlled trials were included (3382 participants). Most were of low quality. The findings of the review may not be wholly relevant to primary care as most of the trials were conducted in a hospital setting and over half involved ear cleaning as part of the treatment (this is generally not available in primary care). However, the review does demonstrate that topical treatments alone are effective at treating acute otitis externa. There was little to choose between them in terms of effectiveness. However, when treatment needs to be extended beyond one week acetic acid drops appear to be less effective than antibiotic/steroid drops. In addition, symptoms persist for two days longer in those treated with acetic acid. More research is needed to determine the effectiveness of steroid-only drops. Patients treated with antibiotic/steroid drops can expect their symptoms to last for approximately six days after treatment has begun." ]

[ "A total of seven randomized controlled studies met the inclusion criteria and enrolled a total of 606 participants. Because of differences in the way that the studies were designed, we were unable to combine their reported results. The results from individual studies that compared heparin at a dose of 1 to 2 IU/mL under continuous pressure were imprecise and do not provide definitive evidence of a difference. The effective dose of heparin has not yet been determined. This evidence needs to be confirmed in future trials. All studies had a moderate to high risk of methodological bias. The review of trials therefore revealed that more research is needed to determine exactly how long an arterial catheter maintained with a normal saline flush solution can be in place and remain functional (to accurately measure blood pressure and pulse and to provide blood samples that can be used to monitor oxygenation and other variables)." ]

[ "We included nine randomised controlled trials (20,101 employees) and nine cohort studies (1280 employees) that examined the effects of training and the use of assistive devices on preventing low-back pain and reducing back-related disability. We found no studies that examined the effects of training or the use of assistive devices as part of a treatment plan for back pain. We found moderate quality evidence that reports of back pain, back-related disability or absence from work were similar between groups who received training on proper lifting techniques and assistive devices compared to a control group that received either no training, minor advice only, professional education, exercise training or back belts. Reports of back pain were also similar between those who received intensive training and those who received shorter instruction. These findings were consistent when measured in the short-term or long-term and when examined in randomised trials or cohort studies. These results are similar to other reviews that examined a range of possible prevention measures. Some of the other reviews found that workers who received training were satisfied and demonstrated increased knowledge on the subject, but this did not appear to consistently translate into behaviour change. In conclusion, training workers in proper material handling techniques or providing them with assistive devices are not effective interventions by themselves in preventing back pain. Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate." ]

[ "We found a total of five randomised clinical trials (involving 1466 women). In three of the trials (involving 1268 women), oral methylergometrine was compared with placebo (two trials) or the Japanese traditional herbal medicine Kyuki-chouketsu-in (one trial). The other two trials (involving 198 women) did not report information on relevant outcomes of interest for this review. Overall, there was no clear evidence that prophylactic oral methylergometrine was effective in reducing haemorrhage after childbirth. The trials were not of good quality and adverse events were not well-reported. We did not find any completed trials looking at the effectiveness of homeopathic remedies in reducing haemorrhage after childbirth. The effectiveness of such remedies warrants further investigation." ]

[ "The benefits and risks of multiple-micronutrient supplementation during lactation are not clear from randomised controlled studies. Key vitamins and minerals, particularly iodine, iron and zinc, are required in small amounts to ensure normal body metabolism, physical growth and development. Nutrient deficiency affects nearly one third of the world’s population, especially in low- and middle-income countries. Breastfeeding mothers need higher levels than usual in order to provide sufficient vitamins and minerals for their own health and that of their babies, particularly for normal functioning and the growth and development of the baby. Previous studies have assessed supplementation of individual micronutrients. This review looked at the use of multiple-micronutrient supplements for breastfeeding women for improving outcomes for the mother and her baby. We searched for studies on 30 September 2015 and identified two small studies (involving 52 women) for inclusion in this review. The studies were carried out in Brazil and the USA and included women who had a low socioeconomic status. The studies were poorly reported and this lack of information made it difficult to determine whether the studies were at risk of bias. Neither of the studies provided data for any of this review's important outcomes: maternal illness (fever, respiratory infection, diarrhoea), adverse effects of micronutrients within three days of taking them, infant death (defined as a child dying before reaching one year of age). Similarly, there were no data for any of the other outcomes that we were interested in. For the mother, these outcomes were maternal anaemia, and women's satisfaction. For the baby, these outcomes were micronutrient deficiency; illness episodes (fever, respiratory infection, diarrhoea, other), adverse effects of micronutrients within three days of the woman receiving the supplement. However, one of the included studies reported that multiple-micronutrient supplementation was effective for lactating women recuperating from anaemia. There is a need for high-quality studies to assess the effectiveness and safety of multiple-micronutrient supplementation for breastfeeding women for improving outcomes for the mother and her baby. Larger studies with longer-term follow-up would improve the quality of studies and provide stronger evidence. Further research should focus on whether multiple-micronutrient supplementation during lactation (compared with no supplementation, a placebo or supplementation with fewer than two micronutrients) is beneficial to the mother and her baby and any associated adverse effects of the intervention. Futher studies should report on important outcomes such as those listed in this review and consider the risks of excess supplementation. Future studies could more precisely assess a variety of multiple-micronutrient combinations and different dosages and look at how these effect outcomes for the mother and her baby." ]

[ "This summary of a Cochrane review of 22 studies with 8275 participants (search update: 15 August 2012) presents what we know from research about the effect of opioids on osteoarthritis (OA). We searched scientific databases for clinical trials looking at pain, function, safety, and addiction of oral or transdermal opioids compared with placebo or no intervention in people with knee or hip osteoarthritis. The review shows that in people with osteoarthritis: - Opioids have a small effect on pain or physical function. - Opioids probably cause side effects. However, we do not have precise information about rare but serious side effects. What is osteoarthritis and what are opioids? OA is a disease of the joints, such as your knee or hip. When the joint loses cartilage, the bone grows to try to repair the damage. Instead of making things better, however, the bone grows abnormally and makes things worse. For example, the bone can become misshapen and make the joint painful and unstable. This can affect your physical function or ability to use your knee. Opioids are generally conceived as powerful pain-relieving substances that are used for the pain of cancer or osteoarthritis. Some examples of opioids are codeine-containing Tylenol® (1, 2, 3, and 4), hydromorphone (Dilaudid), oxycodone (Percocet, Percodan), morphine, and others. They can be taken in a pill form, as an injection, or as a patch placed on the painful area. Best estimate of what happens to people with osteoarthritis who take opioids Pain - People who took opioids rated improvement in their pain to be about 3 points on a scale of 0 (no pain) to 10 (extreme pain) after one month. - People who took a placebo rated improvement in their pain to be about 2 points on a scale of 0 (no pain) to 10 (extreme pain) after one month. Another way of saying this is: - 41 people out of 100 who used opioids responded to treatment (41%). - 31 people out of 100 who used placebo responded to treatment (31%). - 10 more people responded to treatment with opioids than with placebo (difference of 10%). (High-quality evidence) Physical function - People who took opioids rated improvement in their physical function to be about 2 points on a scale of 0 (no disability) to 10 (extreme disability) after one month. - People who took a placebo rated improvement in their physical function to be about 1 point on a scale of 0 (no disability) to 10 (extreme disability) after one month. Another way of saying this is: - 34 people out of 100 who used opioids responded to treatment (34%). - 26 people out of 100 who used placebo responded to treatment (26%). - 8 more people responded to treatment with opioids than with placebo (difference of 8%). (High-quality evidence) Side effects - 22 people out of 100 who used opioids experienced side effects (22%). - 15 people out of 100 who used a placebo experienced side effects (15%). - 7 more people experienced side effects with opioids than with placebo (difference of 7%). (Moderate-quality evidence) Drop-outs because of side effects - 64 people out of 1000 who used opioids dropped out because of side effects (6.4%). - 17 people out of 1000 who used a placebo dropped out because of side effects (1.7%). - 47 more people dropped out because of side effects with opioids than with placebo (difference of 4.7%). (High-quality evidence) Side effects resulting in hospitalisation, persistent disability, or death - 13 people out of 1000 who used opioids experienced side effects resulting in hospitalisation, persistent disability, or death (1.3%). - 4 people out of 1000 who used a placebo experienced side effects resulting in hospitalisation, persistent disability, or deaths (0.4%). - 9 more people experienced side effects resulting in hospitalisation, persistent disability, or death with opioids than with placebo (difference of 0.9%). (Low-quality evidence) Withdrawal symptoms - 24 people out of 1000 who used opioids experienced withdrawal symptoms (2.4%). - 9 people out of 1000 who used a placebo experienced withdrawal symptoms (0.9%). - 15 more people experienced withdrawal symptoms with opioids than with placebo (difference of 1.5%). (Moderate-quality evidence)" ]

[ "Six randomised clinical trials with a total of 710 patients were included in this systematic review. The trials were generally with high risk of bias. We could not demonstrate any significant effect of propylthiouracil on all-cause mortality, liver-related mortality, liver complications, or liver histology of patients with alcoholic liver disease. Although propylthiouracil was not associated with a significant increased risk of non-serious adverse events, there were occasional instances of serious adverse events (leukopenia, generalized bullous eruption). The trials included a small number of patients, and so, the risk of random error (error due to play of chance) is high. There seems to be no evidence for using propylthiouracil for alcoholic liver disease outside randomised clinical trials." ]

[ "We searched for available research up to January 2016 and found 260 studies with different designs. We included a number of non-randomised designs (where investigators did not assign participants to a certain treatment): – 7 comparative cohort studies (a group of people followed over time; six studies compared 968 patients who were taking methylphenidate to 166 controls who were not taking methylphenidate; and 1 study included 1224 patients that were taking or not taking methylphenidate during different time periods); – 4 patient-control studies (comparing two groups of people: 53,192 were taking methylphenidate, and 19,906 were not); – 177 non-comparative cohort studies (2,207,751 participants) with no control group (i.e. who were not taking methylphenidate); – 2 cross-sectional studies (96 participants were taking methylphenidate at a single time point); and – 70 patient reports/series (206 participants were taking methylphenidate). We also included methylphenidate groups from randomised clinical trials (RCTs; experiments in which participants are randomly put into independent groups that compare different treatments). All RCTs assessed methylphenidate versus other interventions for ADHD and follow-up periods from RCTs. We only used the data from the intervention arm with methylphenidate. In all the included non-comparative cohort studies, 2,207,751 participants were taking methylphenidate. Participants' ages ranged from 3 years to 20 years. The findings suggest that methylphenidate administration might lead to serious adverse (harmful) events, including death, cardiac problems, and psychotic disorders. About 1 in 100 patients treated with methylphenidate seemed to suffer a serious adverse event. Withdrawal from methylphenidate due to serious adverse events occurred in about 1.2 out of 100 patients treated with methylphenidate. Withdrawal from methylphenidate due to any adverse events occurred in about 7.3 out of 100 patients treated with methylphenidate. We also noted a large proportion of non-serious adverse events. More than half the patients exposed to methylphenidate seemed to suffer one or more adverse events. Withdrawal from methylphenidate due to non-serious adverse events occurred in about 6.2 out of 100 patients exposed to methylphenidate. Withdrawal of methylphenidate for unknown reasons was 16.2 out of 100 patients exposed to methylphenidate. The quality of the evidence and hence the certainty or reliability of the evidence for the comparative studies is very low. The reliability of the evidence for the non-comparative studies is low due to weaknesses in study design. Accordingly, it is not possible to accurately estimate the risks of adverse events in children and adolescents prescribed methylphenidate. Methyphenidiate might be associated with a number of serious adverse events. Methylphenidate produces a large number of other non-serious harmful effects in children and adolescents with ADHD. We suggest that clinicians and parents are alert to the importance of monitoring adverse events in a systematic, meticulous manner. If methylphenidate is to continue to have a place in ADHD treatment in the future, we need to identify subgroups of patients in whom the benefits of methylphenidate outweigh the harms. Just as we need to be able to identify who is likely to benefit from treatment, we also need to be able to identify those who are most at risk of experiencing adverse events. In order to do this, we need to undertake large-scale, high-quality RCTs along with other studies aimed at identifying those who respond and those who do not respond to treatment." ]

[ "One study found that all patients improved during the study period, but the treatment effect did not differ between the group who received rTMS and the group who received sham rTMS. The other study administered more sessions and reported higher levels of improvement of panic symptoms in those people who received rTMS compared to those who received sham rTMS. Although neither trial reported any serious side effects, they provided only very low quality evidence for adverse event outcomes. On the basis of the limited quality of the evidence available we were unable to determine how safe rTMS is. The limited information available from these two studies is insufficient to conclude whether rTMS is effective in reducing the severity of panic disorder symptoms. The main limitation of this review was that the number of people with panic disorder who were involved was too small. To find out more about rTMS for panic disorder, there is a need for more studies to be carried out which involve larger numbers of people and compare sham rTMS with real rTMS." ]

[ "We included 21 randomised clinical trials in this review. All trials had high risk of bias ('systematic error'). A total of 2348 people were randomised either to somatostatin analogues or a control in the 21 trials. The overall number of people with postoperative complications was lower by 30% in the somatostatin analogues group but there was no difference in postoperative mortality, re-operation rate or overall length of hospital stay between the groups. Pancreatic fistula is drainage of pancreatic juice secreted by the remaining pancreas to the exterior. This was lower in the intervention group by 34%. The proportion of these fistulas that resulted in change to the treatment given to the participants is not clear. When we included trials that clearly distinguished fistulas that required change to the treatment given to the participants, there was no difference between the two groups. Participant quality of life was not reported in any of the trials. In conclusion, somatostatin analogues reduce the incidence of pancreatic fistula. Further trials with sufficient participant numbers and a low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in people undergoing pancreatic resection." ]

[ "The included studies are not easily comparable because of differences in the treatment being studied, the dosage of these treatments, the length of study (and other differences in the study methods), and differences in the types of participants included for the research. The studies were generally well designed in order to reduce the possibility of bias, although for most studies the methods describing how participants were randomised were not described in detail. Otherwise, the risk of bias was low for most studies in the other categories. Serious side effects of treatment were uncommon, except for nerve damage in a long-term trial of dichloroacetate in adults. One trial studied high-dose coenzyme Q10 treatment. This treatment had no clinical benefit. Three trials used creatine monohydrate: one trial reported improved muscle strength and biochemical measurements, but the other two trials reported no benefit (total of 38 participants). One trial studied the effects of a combination of coenzyme Q10, creatine monohydrate and lipoic acid, and reported a statistically significant improvement in biochemical measurements and ankle strength, but no clinical improvement (16 participants). Five trials studied the effects of dichloroacetate: three trials in children showed a statistically significant improvement in biochemical measurements but no clinical benefit on physiological measurements and exercise tests (total 63 participants); one trial of short-term therapy in adults demonstrated no clinical improvement in physiological measurements (total eight participants), and one longer-term trial in adults was terminated prematurely due to adverse effects without clinical benefit (using a combined scale of treatment effect, in 30 participants). One trial using dimethylglycine showed no significant effect on biochemical markers in five participants. One trial using a whey-based supplement demonstrated statistically significant improvement in biochemical markers but no clinical benefit in muscle strength or on health questionnaires (13 participants). Further randomised controlled trials of high quality are needed. They should strictly address outcomes which are relevant to patient care and quality of life, and study these in particular subtypes of mitochondrial disease at a time. The current repertoire of nutritional supplements have been not shown to be effective and future trials should study new treatments." ]

[ "We identified two trials with 156 participants for this review. The comparisons included in these two trials were 1) percutaneous cholecystostomy plus laparoscopic cholecystectomy (key hole removal of gallbladder) immediately after the general condition improves (percutaneous cholecystostomy followed by early laparoscopic cholecystectomy) versus planned delayed laparoscopic cholecystectomy performed routinely (1 trial; 70 participants) and 2) percutaneous cholecystostomy versus conservative treatment (supportive treatment and antibiotic treatment) (1 trial; 86 participants). Both trials were at high risk of systematic error (prone to arrive at wrong conclusions because of the way the trials were designed and data were analysed). There was no significant difference in the proportion of participants who died or developed complications between any of the comparison groups. Quality of life was not reported in any of the trials. There was no significant difference in the proportion of participants requiring conversion to open cholecystectomy in the only comparison that reported this outcome (percutaneous cholecystostomy followed by early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy). The mean total hospital stay and mean costs were significantly lower in the percutaneous cholecystostomy followed by early laparoscopic cholecystectomy group compared with the delayed laparoscopic cholecystectomy group. Because of the few trials included in this review and due to their low sample size, there is risk of random errors (play of chance). Based on the current available evidence, we are unable to determine the role of percutaneous cholecystostomy in the clinical management of high-risk surgical patients with acute cholecystitis. There is a need for well-designed clinical trials with low risk of systematic error and random errors on this issue." ]

[ "In the present review we assessed the evidence for the efficacy, acceptability and tolerability of citalopram in comparison with all other antidepressants in the acute-phase treatment of major depression. Thirty-seven randomised controlled trials (more than 6000 participants) were included in the present review. In terms of efficacy, citalopram was more efficacious than other reference compounds like paroxetine or reboxetine, but worse than escitalopram. In terms of side effects, citalopram was more acceptable than older antidepressants, like tricyclics. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations including differences in efficacy and side-effect profiles." ]

[ "We searched scientific sources to identify eligible trials and found 15 studies with 755 patients. The evidence is up to date to April 2015. Fourteen studies compared prophylactic FFP against no FFP and one study compared two types of FFP, both used therapeutically. No studies reported on all outcomes. There was either high risk of bias, or unclear risk, in the majority of trials included in this review. Our primary outcome was death within 30 days after surgery. Six trials (with 287 patients) looked at this outcome and found no clear difference in mortality between the treatment arms but the quality of the evidence was very low. There was also no difference in the amount of blood lost in the first 24 hours following surgery (measured in five trials; low quality evidence), or the risk of returning to theatre for a reoperation (measured in eight trials; moderate quality evidence). Patients who had FFP received significantly more red blood cells, suggesting that FFP may not be effective in this setting (moderate quality evidence). Measurement of a blood test used to assess blood clotting (prothrombin time) was reported in eight trials and showed that clotting was improved by the use of prophylactic FFP (moderate quality evidence). However, the difference was too small to make a difference in clinical practice. Only one included study reported adverse events as an outcome and reported no adverse events due to FFP transfusion. The review found no evidence for the efficacy of FFP for the prevention of bleeding in heart surgery and it found some evidence of an increased overall need for red cell transfusion in those treated with FFP. There were no reported adverse events due to FFP transfusion. Overall the evidence for the safety and efficacy of prophylactic FFP for cardiac surgery is insufficient. The trials focused on prevention of bleeding and did not address prevention of bleeding for patients with abnormal blood clotting or for the treatment of bleeding patients." ]

[ "The five studies that were included in the review were published between 1995 and 2009 and involved a total of 2277 participants. Four countries were represented (two studies from France and one each from Italy, Sweden, and the Czech Republic). One study involved children and the remaining four trials included only adults. Four of the studies included cancer patients and one included patients in an intensive care unit. We classified the time intervals between dressing changes as short (2 - 5 days) in the more frequently changed dressings group and long (5-15 days) in the less frequently changed group. All studies used transparent dressings made of synthetic materials and two studies used gauze (a fabric dressing that does not stick to the skin) secured with tape when skin was damaged. CVAD dressings were monitored on a daily basis in all trials and participants were followed up at least until the CVAD was removed or until discharge. In one study, the manufacturer provided one of the products, but had no influence in the design or how the results were analysed and reported. The current evidence leaves us uncertain whether the frequency of dressing changes for CVADs influences risk of CRBSI or death. Of particular interest to patients are problems that may be associated with the dressing themselves, such as pain when they are removed and the skin damage that the dressing may cause. We found no clear evidence that pain, which was assessed daily, was affected by the frequency of dressing changes. The quality of the evidence was very low or low. We downgraded quality because of small and few studies, poor study designs and differences in results between the studies. Better designed studies are still needed to show whether longer interval or shorter intervals between dressing changes are more effective in preventing catheter related infections, mortality, skin damage, dressing removal pain, quality of life and cost. This plain language summary is up-to-date as of 10 June 2015." ]

[ "We included 21 randomised controlled trials involving 1197 participants in this review. The trials were mostly at moderate to high risk of bias. Compared with placebo, UDCA showed improvement in itching in five trials (228 women), no benefit was observed in one trial (16 women) and one trial reported improvement only in women with severe disease (94 women). Distress in the unborn baby or symptoms of asphyxia were reported in five trials (304 women) and although there were fewer instances of fetal distress in the UDCA groups compared with placebo, the difference was not significant. The results from the four trials comparing SAMe and placebo were conflicting. Two trials (48 women) reported better pruritus scores for SAMe compared with placebo and two trials (34 women) reported no significant differences between groups for the disappearance of their pruritus. Comparisons of guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling or Yiganling (used in Chinese medicine for their liver-protective properties) with placebo or one with another was based on data from one trial. Further trials are required before any firm conclusions might be made about their effectiveness. One trial (63 women) compared early delivery versus expectant management. There were no stillbirths or neonatal deaths in either group. No significant differences in caesarean section, passage of meconium-stained liquor or admission to neonatal intensive care unit were observed." ]

[ "There are a range of treatment options for urticaria, of which the most well-known are the H1-antihistamines. This review evaluated the efficacy and safety of a similar category, the H2-antihistamines, and included 4 low-quality studies, which examined 144 participants. No firm conclusions could be drawn, but the combination of ranitidine with diphenhydramine appeared to be slightly more effective in reducing the symptoms of urticaria than diphenhydramine alone. In one study, cimetidine appeared to be as effective as diphenhydramine. However, the combination of both drugs was more effective than diphenhydramine alone. Drowsiness and sedation were reported with diphenhydramine, but there was no significant difference in the level of sedation with either famotidine or diphenhydramine. The studies were rather old and considered very few outcomes that were of importance to people with urticaria. Therefore, there is currently insufficient evidence to indicate whether this type of medication is effective or not." ]

[ "We reviewed studies that compared these two highly effective methods and found the IUD to be better at preventing pregnancy than depot medroxyprogesterone acetate (DMPA). Relevant to HIV positive women are the results of one small trial that found that women using the IUD for contraception where less likely to experience a worsening of their HIV disease than those using hormonal contraception. A large, high quality study is urgently needed to shed light on these findings." ]

[ "We searched for and summarized all the randomized controlled trials that looked at using these drugs to treat bleeding or pain related to an IUD. We also included trials that studied the use of these drugs to prevent these problems. We found 15 trials from 10 countries, with more than 2700 women studied. These drugs reduced both bleeding and pain with intrauterine device use. Whether one drug is better than another was not clear. Similarly, the best dosing was not clear. Preventive treatment with these drugs around the time of IUD insertion had mixed results. No serious problems were reported, but stomach upset and sleepiness can occur with this class of drugs. Because of their safety, low cost, and wide availability, these drugs are appropriate treatment for women who have troublesome bleeding or pain with IUD use." ]

[ "We identified 10 randomized controlled trials (studies where participants are randomly allocated to either an experimental or a control group) involving 1458 participants up to December 2018. Seven of the trials (1285 participants) provided findings on the number of deaths, serious adverse events, and lung injuries in the three months following oxygen therapy in the ICU. Lung injury was measured according to participants developing acute respiratory distress syndrome or pneumonia. Five trials included adults admitted to an ICU caring for patients with a range of serious health conditions and one to a surgical ICU. Two trials involved adults with traumatic brain injury; one trial adults after cardiac arrest and resuscitation; and one trial adults with stroke. All participants in six trials received invasive mechanical ventilation directly through a tube into the main airway. In one trial some of the participants were on mechanical ventilation, whilst others received non-invasive oxygen administration. Three trials involved adults receiving non-invasive oxygen. All trials compared more with less oxygen, however using very different levels of oxygen supplementation. Oxygen therapy was given for timeframes ranging from one hour to the length of hospital admission. We are uncertain about the effects of higher levels of oxygen as our findings are based on very low-certainty evidence. We found no evidence for a beneficial effect of higher compared with lower supplemental oxygen levels for adults admitted to ICU. Higher levels of oxygen may have increased the risk of death (4 trials; 1135 participants) and serious adverse events (6 trials; 1234 participants). There was no evidence of a difference in lung injuries with the use of higher supplemental oxygen compared with lower supplemental oxygen, but the evidence is very uncertain (5 trials; 1167 participants). None of the included trials reported on quality of life at any time point, acute myocardial infarction, and stroke. Only one trial reported on sepsis. The numbers of participants enrolled in the trials were too small to permit a definitive judgement about the review findings. The trials varied in the types of illness of the participants, their associated clinical care, disease severity, the targets for how much oxygen was given, and for how long. Two of the trials had a low risk of bias other than for lack of blinding of participants and personnel. Overall all included trials had a high risk of bias." ]

[ "N-acetylcysteine is an antioxidant with strong anti-inflammatory effects that is used in treating endotoxaemia and overdoses of acetaminophen. This Cochrane review of 41 randomized controlled trials with 2768 critically ill adult patients found no evidence to support the theory that N-acetylcysteine might reduce the risk of death in adults with SIRS or sepsis. Intravenous N-acetylcysteine did not affect the length of stay in the intensive care unit, duration of mechanical ventilation, duration of support for the cardiovascular system or incidence of new organ failure. There is currently insufficient evidence to support the use of N-acetylcysteine in SIRS or sepsis. We also found that when N-acetylcysteine was administered more than 24 hours after the development of clinical signs of SIRS or sepsis it may even be harmful, by causing cardiovascular depression. Twenty of the trials used N-acetylcysteine in patients around the time of surgery, including cardiac, vascular and major abdominal surgery, and liver transplantation. Eight studies evaluated N-acetylcysteine in patients with severe sepsis or septic shock associated with the medical conditions acute respiratory distress syndrome (ARDS), multiple organ failure, liver failure, malaria or burns. The dosing of N-acetylcysteine, timing and duration of treatment, from a single intravenous dose to infusions up to seven days, varied. Twenty papers had a low risk of bias." ]

[ "We included 19 RCTs involving 13,209 women of childbearing age. The trials compared: - tubal rings versus clips (six RCTs, 4232 women); - partial salpingectomy versus electrocoagulation (three RCTs, 2019 women); - tubal rings versus electrocoagulation (two RCTs, 599 women); - partial salpingectomy versus clips (four RCTs, 3827 women); - clips versus electrocoagulation (two RCTs, 206 women); and - two types of clips, i.e. Hulka clips versus Filshie clips (two RCTs, 2326 women). We found no RCTs that investigated sterilisation by chemicals or tubal inserts, so all the included studies involved an abdominal operation. There were no deaths reported with any method, and major and minor morbidity were rare. Pregnancy rates were less than 5/1000 procedures one year after surgery. Complicationrates (problems after surgery/minor morbidity) were very low for all methods compared. Minor complications, including pain, and technical failures were more common with rings than clips. Major morbidity and postoperative pain were more common with partial salpingectomy than with electrocoagulation. Postoperative pain was reported twice as often by women sterilised by tubal rings than those sterilised by electrocoagulation.Technical failures were more common with clips than cutting and tying techniques, but operating time was shorter for clips. We found little evidence concerning women's or surgeon's satisfaction. Tubal sterilisation by cutting and tying the tubes, or using electric current, clips or rings, is an effective method of contraception with few problems. The choice of method will depend upon the surgeon's experience, availability of equipment, setting, and cost. More research is needed about methods for tubal sterilisation that do not require an abdominal operation." ]

[ "we included seven studies (total participants = 494). All studies were on full-term, healthy infants who were breastfeeding fully or partially. There were two main comparisons: fluid supplementation via intravenous route versus no fluid supplementation and fluid supplementation via intravenous route versus oral route (by increasing feeding by mouth). Most studies did not provide enough information on certain key aspects of the methods employed. Notably, in all studies, care personnel could not be masked from knowing whether or not the infants received additional fluid, and if so through which route, and this might have affected the interpretation of results, especially those that required a person to make a judgement. none of the included studies reported funding. no infant in either the fluid supplementation or no fluid supplementation group developed clinical complications related to excessive bilirubin. Serum bilirubin was slightly lower at four and eight hours after treatment in fluid-supplemented infants. Beyond eight hours, bilirubin levels were very similar whether or not additional fluid was given. Infants who received additional fluid appeared to have shorter duration of phototherapy (on average 10.70 hours shorter, participants = 218, studies = three) and lower risk of requiring exchange transfusion (on average 1% lower, participants = 462, studies = six), but in both analyses, inconsistent results among the included studies have weakened our confidence in the overall estimates. There were no differences in breastfeeding frequencies in the first three days between infants who received additional fluid and infants who did not. In another comparison, one study showed that there were no clear differences between infants who received intravenous and oral fluid supplementation in all measurements (called outcomes), including blood bilirubin and the rate of change of bilirubin levels after four hours of study, as well as the number of infants who required exchange transfusion. there was no evidence on the major clinical outcomes of bilirubin-associated brain problems, as no infants in either group developed these problems. There was low- to moderate-quality evidence for all major outcomes. Three main factors affected the quality of evidence: first, the use of bilirubin, a laboratory measurement, as the main outcome, rather than direct clinical outcomes that matter to patients; second, inconsistent study results; and third, unpublished studies that might change the review findings for the relevant outcomes. there is no evidence that intravenous fluid supplementation affected major clinical outcomes such as acute- or long-term brain problems associated with excessive bilirubin in healthy, full-term newborn infants, mainly because the baseline risk of developing such problems was very low in this group of infants. Intravenous fluid supplementation may reduce serum bilirubin at certain time points but it is unclear whether this translates into important clinical benefits. Future research should focus on higher-risk populations such as preterm infants or infants with haemolysis (increased red blood cell breakdown which causes a rapid rise in bilirubin)." ]

[ "We identified 17 randomized controlled trials comparing TEG- or ROTEM-guided use of blood transfusion to guidance from the clinical judgement of doctors or standard laboratory tests, or both. The included trials were conducted mainly in adults in need of cardiac surgery, and involved 1493 participants. In terms of efficacy, the use of TEG or ROTEM tests seem to reduce the need for all types of blood transfusions. However, we could not find fewer participants in need of further operations due to continuous bleeding, or at risk of massive bleeding with transfusion. Despite signs of benefit in regards to survival, our findings are hampered by the overall low quality of included studies. Assessment of harms indicated a reduced risk of kidney failure, while no other significant adverse -events were found. However, the reported adverse event rates were very low. All included trials except two were marred by high risk of bias. Due to few events and many poorly designed trials, we consider our overall findings to be of low quality evidence in favour of TEG and ROTEM use in the management of bleeding patients." ]

[ "We searched the literature up to 10 September 2014 and tried to find all available research (published and unpublished) that compared these two types of defibrillators. We only included trials with a high-quality study design to avoid the possibility of inaccurate results. Four trials (552 participants) met the inclusion criteria of our review. Several included trials were potentially at risk of misleading results due to features of their study design. When we combined these trial results, we found that using the newer biphasic waveform defibrillators may be associated with lower failure rates of restarting a person's heart, but these results were imprecise. There was no difference in the number of people who were alive on arrival at the hospital or who were discharged from the hospital alive. No included trials reported on side effects or operator safety. We are uncertain as to whether biphasic defibrillators have an important effect on being able to restart a person's heart because the results were imprecise." ]

[ "This review is current to 21 March 2019. We found 14 randomized controlled studies that enrolled a total of 1844 adult participants. Six different classes of medicines were tested. These were antipsychotic drugs used as tranquillizers in ten studies; the sedative alpha2 agonist dexmedetomidine in three studies; statins that reduce cholesterol in two studies; opioids as part of pain management in one study; serotonin antagonists for nausea and vomiting in one study; and cholinesterase inhibitors, which are medicines for Alzheimer's disease, in one study. Ten studies compared medicine to placebo - an inactive medicine also known as a sugar pill; four studies compared different drugs. Eleven studies with 1153 participants reported on the main outcome of this review - duration of delirium. When drug classes were directly compared with placebo, only the alpha2 agonist dexmedetomidine was found to reduce the duration of delirium, and the cholinesterase inhibitor rivastigmine was found to prolong the duration of delirium. Each of these results is based on findings from a single small study. The other drugs when compared to placebo did not change delirium duration. The Review authors used the statistical method of network meta-analysis to compare the six different drug classes. Dexmedetomidine was ranked most effective in reducing delirium duration, followed by atypical antipsychotics. However, network meta-analysis of delirium duration failed to rule out the possibility of no difference for all six drug classes compared to placebo. Using this method, we did not find that any drug improved the duration of coma, length of stay, long-term cognitive outcomes, or death. The alpha2 agonist dexmedetomidine shortened time spent on a breathing machine. Adverse events often were not reported in these trials or were rare when reported. An analysis of reported events showed that events were similar to those reported with placebo. We found 10 ongoing studies and six studies awaiting classification that, once published and assessed, may change the conclusions of this review. Most of the included studies were small but of good design. Nine of the 14 studies were considered to have low risk of bias." ]

[ "Of the seven randomised controlled trials that we found, only two trials including 186 people had useable data. The analysis of these two small trials showed inconsistent effects of aromatherapy on measures of agitation, behavioural symptoms and quality of life. More large-scale randomised controlled trials are needed before firm conclusions can be reached about the effectiveness of aromatherapy for dementia." ]

[ "We searched for well-designed trials to see the effect of TENS compared to 'sham' TENS in people with SCD for relieving pain, reducing the intensity of pain, reducing the frequency of pain episodes, making a difference to the use of painkillers, improving quality of life and for assessing any adverse effects. We only found one trial (22 participants aged between 12 and 27 years). The participants were graded into four groups according to how severe their pain was. On the first visit, the participants from different groups were chosen randomly to receive either TENS or ‘sham’ TENS treatment. For a further crisis of the same severity participants were given the alternative intervention to the first one. For those experiencing a pain episode of a different severity, it is not clear which treatment they were given. Neither the participant nor the researcher were aware of which treatment was received. 30 episodes (across 22 participants) of TENS treatment and 30 of 'sham' TENS treatment were analysed. Due to low-quality data and issues with the trial design, we can only report in a descriptive way without any formal analysis. Caution should be used in interpreting these results. In the included trial no difference was found in the rating of pain on a scale of 1 to 10 at the end of one hour and four hours between the TENS and 'sham' TENS treatment groups. There was no difference between groups as to how much pain medication was used. Given the very low quality of the evidence, we are also uncertain whether TENS improves overall satisfaction as compared to 'sham' TENS. A minor adverse effect of itching was reported by only one person receiving TENS, whereas two people receiving 'sham' TENS reported a worsening of pain with the intervention. Since there is only one included trial with very low-quality evidence, we cannot state whether TENS makes any difference to managing pain in people with SCD. The trial publication did not clearly report how the randomised list for allocating the participants to the two treatment groups was generated, therefore, we assessed this as having a high risk of bias. The reporting and analysis was based on only the total number pain events and not the number of people reporting pain episodes. It is unclear from this report how many participants were crossed over from TENS to 'sham' TENS treatment group. The first treatment may have an effect on the subsequent treatment and there is no clear data regarding the cross over process from one treatment group to the other. Hence we conclude that the trial has a high risk of bias and the results are hard to interpret." ]

[ "We reviewed 24 controlled clinical trials with 4631 participants investigating the effectiveness of several different Echinacea preparations for preventing and treating common colds or induced rhinovirus infections. Our review shows that a variety of products prepared from different Echinacea species, different plant parts and in a different form have been compared to placebo in randomized trials. Due to the significant differences in the preparations tested, it was difficult to draw strong conclusions. Five trials were rated as having a low risk of bias in all five categories of the Cochrane 'Risk of bias' tool. Five more trials were rated as low risk of bias, having an unclear risk of bias in only one category. Eight trials were rated as having a high risk of bias in at least one category and the remaining six as having an unclear risk of bias. The majority of trials investigated whether taking Echinacea preparations after the onset of cold symptoms shortens the duration, compared with placebo. Although it seems possible that some Echinacea products are more effective than a placebo for treating colds, the overall evidence for clinically relevant treatment effects is weak. In general, trials investigating Echinacea for preventing colds did not show statistically significant reductions in illness occurrence. However, nearly all prevention trials pointed in the direction of small preventive effects. The number of patients dropping out or reporting adverse effects did not differ significantly between treatment and control groups in prevention and treatment trials. However, in prevention trials there was a trend towards a larger number of patients dropping out due to adverse events in the treatment groups. The evidence is current to July 2013." ]

[ "Our review included 10 studies (830 participants, 1387 eyes) published between 1998 and 2012. Nine of these studies investigated the ability of OCT to diagnose CSMO. Study funding sources There were no overt declarations of potential conflicts of interest in terms of the manufacturer of the OCT device being involved in funding the research. Key results We found that OCT retinal thickness measurement is not sufficiently accurate to detect CSMO, involving the centre of the macula, using clinical fundus examination as the reference standard. Of 10 patients with diabetic retinopathy, 5 of whom have CSMO, 1 of 5 with no CSMO would be wrongly diagnosed as having CSMO, and about 1 of 5 with CSMO would be missed. However, researchers have found that disagreements between OCT and clinical examination occur because OCT can detect early, subclinical retinal thickening in people without CSMO and more advanced retinopathy. They suggested that such cases of subclinical macular oedema are followed more closely, since they are at increased risk of progression to CSMO. Furthermore, OCT is an essential tool to manage antiangiogenic therapy in patients with DMO and is believed by many to be a new reference standard for its diagnosis. Quality of the evidence Study quality was often unclear because of incomplete reporting or because it was at risk of bias. Specifically, this concerned how patients were selected in the study, who referred them and how, and exclusion of those for whom poor quality images were obtained. Furthermore, many studies included both patient's eyes, which is a problem in data analyses." ]

[ "On 25th October 2011, the European Medicines Agency issued a press release on the worldwide withdrawal of Xigris® (human recombinant activated protein C) from the market by Eli Lilly due to lack of beneficial effect on 28-day mortality in the PROWESS-SHOCK trial. Furthermore, Eli Lily has announced the discontinuation of all ongoing clinical trials. APC should not be used for sepsis or septic shock outside randomized clinical trials. Current evidence does not support the use of human recombinant activated protein C in adults or children with severe sepsis or septic shock; moreover, there is an increased risk of bleeding associated with its use." ]

[ "This review update assessed evidence from 2641 participants in 20 randomised, double blind, placebo-controlled clinical trials of oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Oral oxycodone 10 mg plus paracetamol 650 mg provided effective analgesia. About half of those treated experienced at least half pain relief over 4 to 6 hours, and the effects lasting up to 10 hours. Higher doses gave more effect. Associated adverse events (predominantly nausea, vomiting, dizziness and somnolence) were more frequent with oxycodone or oxycodone plus paracetamol than with placebo, but studies of this type are of limited use for studying adverse effects. Limited information about oxycodone on its own suggests that it provided analgesia at doses greater than 5 mg, and that addition of paracetamol made it more effective." ]

[ "Athlete's foot (tinea pedis) is a fungal infection of the feet that is easily spread and difficult to get rid of. This review compared different oral antifungal drugs (i.e. drugs taken by mouth), and it included 15 trials, involving 1438 participants. There are several different kinds of oral treatments, and the trials we found considered all the oral drugs used to treat athlete's foot. We found terbinafine and itraconazole to be more effective than placebo. And we found terbinafine to be more effective than griseofulvin. Griseofulvin is a treatment that was developed much earlier than the new treatments, such as terbinafine and itraconazole; these newer treatments tend to be most evaluated. Trials of other drugs were not large enough to show differences between them. All drugs had side-effects; gastrointestinal effects were the most common. In future clinical trials, larger numbers of participants are needed to test different treatments in order to produce more reliable data. Also, future research should consider the costs of the different treatment approaches." ]

[ "Two studies met the inclusion criteria but only one contributed data to the outcomes of interest. The study was based in Denmark. Women less than 20 weeks pregnant were randomly assigned to drinking caffeinated instant coffee (568 women after exclusions) or decaffeinated instant coffee (629 women). Drinking three cups of coffee a day in early pregnancy had no effect on birthweight, preterm births or growth restriction. Both included studies were randomised controlled trials. One randomly allocated pregnant women to either caffeinated or decaffeinated groups. It was unclear from the other whether allocation concealment was undertaken. Blinding of personnel and study participants was satisfactory in both studies while blinding of outcome assessor was not clearly stated. Attrition bias was also not clearly explained in one study. The results from the one trial that provided data for analysis showed that there was no evidence of an effect of caffeine avoidance on the outcomes birthweight, preterm birth or small-for-gestational age. Two outcomes were assessed and assigned a quality rating using the GRADE methods. Evidence for these two outcomes, namely birthweight and frequency of preterm birth, was assessed as of low quality, with downgrading decisions due in part to the relatively small sample sizes and the wide confidence interval of the one included trial that contributed data. There is insufficient evidence to confirm or refute the effectiveness of caffeine avoidance on birthweight or other pregnancy outcomes." ]

[ "Sixteen studies involving 3,005 people are included in this review. We did not find strong evidence that either mechanical or pharmacological interventions reduce death or clots travelling to the lungs, but we found some evidence that they can prevent clots from forming in the legs." ]

[ "This review of pharmacological interventions showed that non-steroidal anti-inflammatory drugs (NSAIDs) may reduce pain in the short term, but overall pain did not improve after three months. There is conflicting evidence on the effect of glycosaminoglycan polysulphate. The anabolic steroid nandrolone may be effective, but associated risks demand extreme caution if used for patellofemoral pain syndrome, particularly in athletes." ]

[ "The flu can be caused by many different viruses. One type is influenza A, with headaches, coughs and runny noses that can last for many days and lead to serious illnesses such as pneumonia. Amantadine and rimantadine are antiviral drugs. The review of trials found that both drugs are similarly helpful in relieving the symptoms of influenza A in adults, but only when there is a high probability that the cause of the flu is influenza A (a known epidemic, for example). It is likely that neither drug will interrupt the spread of influenza A and by treating symptoms may encourage viral spread in the community by people who are feeling better but are still infectious. Resistance of influenza viruses to amantadine is a serious worldwide problem as shown by recent surveys. Both drugs have adverse gastrointestinal (stomach and gut) effects, but amantadine can also have serious effects on the nervous system. They should only be used in an emergency when all other measures fail." ]

[ "We identified 10 studies involving 878 participants. Twenty-eight participants were lost to follow-up. The evidence is current up to 27 October 2015. All participants were recruited from intensive care units (ICUs) and received mechanical ventilation for more than 48 hours. Moderate quality evidence from eight studies involving 759 participants demonstrated that a semi-recumbent (30º to 60º) position reduced clinically suspected VAP by 25.7% when compared to a 0° to 10° supine position. Based on this result, we would expect that out of 1000 critically ill adult patients who are nursed in the semi-recumbent position (30º to 60º) for more than 48 hours, 145 patients would experience clinically suspected VAP compared to 402 patients nursed in the 0° to 10° supine position. There was no significant difference between the two positions in reducing microbiologically confirmed VAP (very low quality evidence), mortality (low quality evidence), length of ICU stay (moderate quality evidence), hospital stay (very low quality evidence), duration of ventilation or use of antibiotics. The main limitations of the evidence were the small numbers of participants contributing data to the analyses and that for some studies researchers would have known which treatment group participants were from (a risk of bias). Only two studies with 91 participants compared different degrees of bed head angle (45° versus 25° to 30° semi-recumbent position). Very low quality evidence showed no statistically significant differences in the effects of VAP (clinically suspected and microbiologically confirmed), mortality (ICU and hospital), length of ICU stay or use of antibiotics. Only one study reported the adverse event of pressure ulcers and did not find a difference between the 45° semi-recumbent and 10° supine positions. No other adverse events, such as thromboembolism, or side effects on heart rate or blood pressure were reported. The balance of the benefit and harm of semi-recumbent positioning still remains uncertain due to the limited numbers of studies and the low quality of the existing evidence. More high quality evidence is required on the effects of the semi-recumbent versus supine position and the optimal body positions." ]

[ "Its use in newborn babies is studied in only one study of 63 babies. Propofol helped to reduce time to complete procedure, time of recovery and time to prepare drugs. However, with this small number of newborns studied, the safety can not be proven. Further studies are warranted." ]

[ "This review identified three trials (involving 360 women and their infants), but one trial did not provide any relevant data. The trials were small and were assessed as being at a low or unclear risk of bias. The trials did not report many outcomes of relevance to this review. We did find limited evidence to suggest that when magnesium sulphate was given to mothers in preterm labour, differences in the dose (high-dose versus low-dose) did not impact on the number of babies that died (very low quality evidence). There were no data to assess other important outcomes: birth less than 48 hours after entry to the trial, or serious outcomes for mothers or their babies. The included trials provided very few data for other outcomes relevant to this review (overall, we were only able to examine eight of the 45 outcomes we wanted to examine). One trial did find that the rate of newborn respiratory distress syndrome (low quality evidence) and the length of stay in the neonatal intensive care unit were reduced with high-dose magnesium sulphate (compared to the babies born to the group of women who were given low-dose magnesium sulphate). However, this result is based on evidence from one small study and should therefore be interpreted with caution. The rate of caesarean birth did not differ between those women given high-dose and those women given low-dose magnesium sulphate. Nor were there any differences between groups in terms of the number of babies that died before birth or during the subsequent month or the number of babies with low levels of calcium in their blood, low bone density or bone fractures. The frequency of self-reported adverse effects in mothers including flushing, headache (two trials, 248 women), or nausea and vomiting (one trial, 100 women) did not differ between high-dose and low-dose magnesium sulphate groups. Pulmonary oedema was reported in two mothers given high-dose magnesium sulphate, and in none of the mothers given low-dose magnesium sulphate. No trials have looked at different durations of treatment, timing and other ways of giving magnesium sulphate to mothers going in to labour too early. Further trials are needed to address the lack of evidence regarding the best dose, duration of therapy, timing of therapy and role for repeat dosing in terms of efficacy and safety for mothers and their children." ]

[ "We conducted a systematic review to assess whether or not cisapride actually relieves constipation and controls the symptoms of irritable bowel disease, in addition to looking at whether or not these effects are worth its use compared to the risk of cisapride's dangerous side effects. Through a detailed look at the literature, we found no clear evidence to suggest that cisapride has a role in controlling symptoms related to constipation or IBS and believe its not worth the risk of its possibly fatal arrhythmia side effects." ]

[ "We looked for trials comparing supplements with placebo (dummy). We included 11 randomised controlled trials (596 participants) when it was clear that the children or adults taking part had atopic eczema. In reviewing the trials, the main outcomes we looked for were evidence of improvement in the symptoms of eczema, such as itching or loss of sleep, in the short-term (i.e. six weeks). In the longer term, we wanted to see evidence of a reduced need for treatment for the eczema or a reduction in the number of flares. We also looked for evidence of any general improvement in the eczema and in individual symptoms. Overall, we found no convincing evidence that taking supplements improved the eczema of those involved. In general, studies were small with low numbers of participants and of poor quality in terms of the way they were run. Two trials of fish oil did find slight improvement for the participants in terms of the degree of itchiness and quality of life. However, these trials had small numbers, which means they had little chance of finding real differences if they did exist. That is why larger trials are needed before any recommendations can be made. We found no evidence of adverse (harmful) effects in those who took part in the trials. People sometimes think that supplements can at least do no harm; however, high doses of vitamin D, for example, can cause serious medical problems, and the safety of dietary supplements should not be assumed. The cost of supplements can also mount up." ]

[ "Six published randomised controlled trials met our inclusion criteria, with a total of 1177 infants enrolled. This update includes the results from two high-quality studies conducted in 760 infants of less than 30 weeks' postmenstrual age (PMA). In our previous update of our review, in 2015, we found that the initial evidence regarding inositol supplementation in preterm babies with RDS was promising. Inositol supplementation lowered rates of death and bleeding in the brain, with an important reduction in eye problems as well. Inositol did not have serious adverse effects. We suggested that further research was warranted to confirm these preliminary findings. Such research has now been published from two high-quality studies that included 760 infants of less than 30 weeks' PMA, the most vulnerable population. All results indicate that there are no reductions in adverse outcomes associated with inositol supplementation, including infant death, eye problems, bleeding in the brain, infections, chronic lung problems and gastrointestinal problems. Thus inositol supplementation in preterm infants is not recommended. Infants enrolled in these studies should be followed into childhood for assessment of any neuro-developmental problems. According to GRADE (a method to score the quality of the trials supporting each outcome), the quality of the evidence varied but was moderate to high for the important outcomes in the analyses for repeated high doses of inositol in infants born at less than 30 weeks' postmenstrual age." ]

[ "Two studies had deaths reported, comprising of four persons in the control group, and eight in the AZA group. These small numbers do not allow a statistical analysis. Conflicting conclusions on potential risk of cancer in MS patients with long-term AZA treatment have been reported in eight published papers, not considered in the present review because they came from sources other than clinical trials. The presence of patients who developed cancer ( three in the AZA and 1 the placebo group) was reported in two out of five studies considered in this review. Numerous studies of AZA treated patient populations other than MS patients are also available. The whole data, however, does not show an increase in risk of malignancy from AZA. Possible long-term risks may be related to a treatment duration above ten years and cumulative doses above 600 g." ]

[ "We found five randomised controlled trials comparing timed intercourse versus intercourse without ovulation prediction, in a total of 2840 women or couples trying to conceive. The evidence was current to August 2014. One large included study (1453 women) has not published usable results and could therefore not be analysed. One study reported live birth rates and found no evidence of a difference; however, the study was too small to have any clinical value. Only one study reported levels of stress and showed no evidence of a difference between timed intercourse with urinary fertility monitoring and intercourse without urinary fertility monitoring. No other adverse events were reported. Only two studies reported clinical pregnancy rates, and showed no evidence of a difference in pregnancy rates in couples with subfertility. The evidence suggested that if the chance of a clinical pregnancy following intercourse without ovulation prediction was assumed to be 16%, the chance of a clinical pregnancy following timed intercourse would be between 9% and 33%. However, if including self-reported pregnancies (not confirmed by ultrasound), pregnancy rates were higher after timed intercourse. The evidence suggested that if the chance of a pregnancy following intercourse without ovulation prediction was 13%, the chance following timed intercourse would be between 14% and 23%. No difference in effect was found between couples trying to conceive for less than 12 months versus 12 months or more. One trial reported time to conception data and showed no evidence of a difference in time to conception. The overall quality of the evidence ranged from low to very low for all outcomes. The main limitations of the evidence were imprecision, poor reporting of clinically relevant outcomes and a high risk of publication bias, as one large study remains unpublished. Therefore, the findings should be regarded with caution." ]

[ "We found 12 studies including 854 women that examined the effect of exercise in women with period pain. The evidence is current to August 2019. Two trials did not report data suitable to be included in the meta-analysis, so we included 10 trials with 754 women in our meta-analysis. Eleven trials compared exercise with no treatment and one compared exercise with NSAIDs. Exercise, whether low-intensity, such as yoga, or high-intensity, such as aerobics, may provide a large reduction in the intensity of period pain, compared to not doing anything. This reduction in pain was likely to be important to women with period pain as it is over twice the minimum amount of pain reduction we think is needed to notice a difference. Most studies asked women to exercise at least three times per week, for about 45 to 60 minutes of exercise each time. It is unclear if exercising less frequently, or for a shorter duration would have the same results. Exercise was performed regularly throughout the month, with some studies asking women not to perform exercise during the period itself. The evidence for the safety of exercise was not well reported and so we cannot draw any conclusions. Other outcomes, such as the effect on overall menstrual symptoms or overall quality of life, were not well reported and the evidence was of very low quality, so we cannot be sure if exercise has any effect on these outcomes. No studies reported on rates of being absent from work or school or on restrictions of daily life activities. There was not enough evidence to determine if there was any benefit of exercise when compared to NSAIDs, a class of medications (like ibuprofen) commonly used to treat period pain, on menstrual pain intensity, need for additional pain-relieving medication, or absence from work or school. No studies reported on quality of life or restriction of daily life activities The quality of the evidence was low to very low. The main limitations were imprecision due to small sample sizes (too few women in the study), inconsistency (studies gave very different results) and risk of bias related to blinding (where researchers or participants knew what treatment they were getting)." ]

[ "In this review we summarized studies of antidepressant drug treatments in patients with MS. We found two studies that met the inclusion criteria of methodological quality, comprising of a total of 70 participants: one (28 participants) reported the effects of desipramine, the other (42 participants) the effects of paroxetine. The two studies showed no improvement of depression with both treatments in the short term (five/twelve weeks). Adverse effects, such as nausea or headache occurred frequently. Further studies on drug treatment of depression in MS with a longer duration are clearly needed, as the results may be affected by the small size of participants and by the fact that many participants did not complete the studies." ]

[ "The evidence is current to February 2016. In this update we identified 10 completed trials that compared giving white blood cell transfusions to treat infection compared to not giving white blood cells to treat infection. One additional trial has not yet been completed. The 10 trials containing a total of 587 participants were conducted between 1975 and 2015. The studies differed in the type of infections they included. Data from three trials were not included in the analyses because participants were included within the trial more than once. Six trials included both children and adults, but results were not reported separately for children and adults. The two newest trials gave G-CSF to donors, both were stopped early due to lack of recruitment. Six studies reported their funding sources and all were funded by governments or charities. Giving white blood cell transfusions to treat infection may not affect the risk of death or the number of people who recover from an infection. It is unknown whether white blood cell transfusions increase the risk of having a serious adverse event. None of the studies reported whether white blood cell transfusions reduced the number of days participants were on therapeutic antibiotics, or whether white blood cell transfusions had an effect on participants' quality of life. The evidence for most of the findings are of low or very low quality. This was because the total number of participants included in this review was too small to detect a difference in this review's primary outcome. We calculated that a study would need at least 2748 participants to be able to detect a decrease in the risk of death from 35 people out of 100 to 30 people out of 100 (five additional lives saved per 100 people treated). Also participants and their doctors were likely to know which study arm they had been allocated to in all of the studies." ]

[ "We found 26 studies with 2272 participants receiving home-based multidimensional survivorship programmes compared with control. The content and delivery approach of the home-based multidimensional survivorship programmes were diverse among the included studies. The survivorship programme could incorporate any combination of at least two of the three identified components: educational (such as the provision of information and advice on how to self-manage); physical (such as exercise or resistance training); and psychological (such as counselling and cognitive therapies). Most of the studies used usual care (routine medical follow-up services) as a comparator. A few studies used a lower level or different type of intervention (e.g. stress management or exercise) or attention control as the comparator. The results revealed that home-based multidimensional survivorship programmes in breast cancer survivors appear to have a short-term beneficial effect of improving quality of life. Several other studies examined the effects of home-based multidimensional survivorship programmes on symptoms and psychosocial outcomes. Those breast cancer survivors who received home-based multidimensional survivorship programmes showed a reduction in fatigue, insomnia and anxiety, but the effect was in the short term. There was no difference between groups with respect to symptoms of depression, flushes and night sweats. We found that a group-based approach may be more effective than an individual-based approach to deliver the home-based multidimensional survivorship programmes. However, we found no evidence for a difference in quality of life with educational, psychological or physical components of the survivorship programmes. The quality of evidence across studies for quality of life ranged from moderate to very low, meaning that in some cases we were fairly confident about the results (e.g. quality of life improvements) while in other cases we were uncertain about the results (e.g. reductions in fatigue, insomnia and anxiety)." ]

[ "Twenty three trials with 3685 participants were included in the review. Participants were more likely to improve if they were using an anticholinergic drug compared with bladder training alone, and also when using a combination of an anticholinergic drug plus bladder training. More people reported an improvement in their overactive bladder symptoms when using electrical stimulation than an anticholinergic drug, but this was only significant in one trial for one type of electrical stimulation, percutaneous posterior tibial nerve stimulation. These results have to be viewed with caution as different types and doses of the anticholinergic drugs were used in the trials. The main adverse effect reported was dry mouth, in about a third of the people taking an anticholinergic drug." ]

[ "We found one trial involving 75 preterm infants with very low-quality evidence on the effects of adding extra prebiotics (a type of carbohydrate) to human milk in preterm infants. A second publication by the same study authors reported different methods regarding blinding and randomisation of the trial. Study authors confirmed that these publications describe the same trial but have not yet clarified which method is accurate. We were unable to reproduce the analyses from the data presented. The search is up-to-date as of February 2018. Prebiotic carbohydrate supplementation increased the mean weight of preterm infants at day 30 and resulted in a shorter hospital stay compared with control. No evidence shows a clear difference in risk of feeding intolerance or necrotising enterocolitis between the prebiotic-supplemented and unsupplemented groups. No other data were available to show the effects of adding extra carbohydrate to human milk on short- and long-term growth, body fat, obesity, brain development, and heart problems. Evidence on the short- and long-term effects of adding extra carbohydrate to human milk in preterm infants is lacking. This systematic review found very low-quality evidence on the effects of adding prebiotic carbohydrate to human milk in preterm infants, along with uncertainties about methods and analysis. The single trial included a small sample of Iranian preterm infants, and so the evidence may be considered as not generalisable. However, the outcomes assessed are common to all preterm infants, and the trial shows that adding prebiotic carbohydrate to human milk is possible in developing countries. Further research is needed to assess the benefits and harms of different types and concentrations of carbohydrate supplementation for preterm infants fed human milk. Currently, digestible carbohydrate supplementation in preterm infants is provided as a component of multi-nutrient human milk fortification. Hence we do not plan to publish further updates of this review." ]

[ "We found only one small randomized controlled trial that compared early feeding (within 24 hours of injury) with conventional feeding (after at least 48 hours). The trial showed no differences between the groups for any of the outcomes examined. Further research in this area is urgently needed to help guide optimal treatment of children with critical illness. In a recent search update (February 2016) we identified a protocol for a relevant randomized controlled study; however, no results have yet been published." ]

[ "This review found six mostly small studies with some limitations in their methods. All six studies were conducted in the neonatal nursery of a major tertiary hospital. In all studies, researchers enrolled preterm infants of average postmenstrual age of 29 weeks (nearly two and a half months preterm). Some studies enrolled twins only; others enrolled twins and triplets and quadruplets and chose to co-bed two of the higher-order multiples considered most stable at the time of enrollment. Overall, researchers reported no differences between the co-bedded group and the group receiving care separately in terms of weight gain, episodes of major disturbances in their breathing, heart rate or oxygenation level (apnea, bradycardia, or desaturation episodes), length of hospital stay, and occurrence of infection. Conflicting results were noted in the two included studies that assessed infants' pain response after heel prick. Overall quality of evidence was low because of limitations in study methods, small sample sizes giving rise to imprecise results, and inconsistency in study results. We can make no recommendations for or against co-bedding for stable preterm twins in the neonatal nursery on the basis of evidence gathered in this review. Further research on this topic is needed." ]

[ "There was evidence of benefit that selective serotonin reuptake inhibitors (SSRIs) were more effective than placebo, although the evidence was of very low quality. There was also evidence of benefit for monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A (RIMAs), and benzodiazepines, even though the evidence was low in quality. The anticonvulsants gabapentin and pregabalin also showed moderate-quality evidence of a clinical response. We did not observe this effect for the remaining medication classes. The SSRIs were the only medication proving effective in reducing relapse based on moderate-quality evidence. There was low-quality evidence that more people taking SSRIs and SNRIs dropped out due to side effects than those taking placebo, but absolute withdrawal rates were low. For the outcome of SAnD symptom severity, there was evidence of benefit for SSRIs, the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine, MAOIs, RIMAs, benzodiazepines, the antipsychotic olanzapine, and the noradrenergic and specific serotonergic antidepressant (NaSSA) atomoxetine, but most of the evidence was of very low quality. SSRIs and RIMAs reduced depression symptoms, and SSRIs reduced functional disability across all domains. We also observed response to long-term treatment with SSRIs (based on low-quality evidence), MAOIs (based on very low-quality evidence), and RIMAs (based on moderate-quality evidence). Most evidence for treatment efficacy is related to SSRIs. Nevertheless, SSRI trials were associated with very low-quality evidence and high risk of publication bias. It would be useful for future studies to evaluate the treatment of SAnD in people with comorbid disorders, including substance use disorders. Trials that provide adequate information on randomisation and allocation concealment are needed." ]

[ "This review of three studies involving 470 participants found little evidence of how this care is best delivered. Information on a small number of nursing home residents who had a stroke (67 participants from a larger trial) showed that training nursing staff improved their knowledge of oral care and resulted in improved oral hygiene in their patients. Another trial demonstrated the beneficial impact of a decontamination gel on the incidence of pneumonia amongst patients in a stroke ward. However, there was no other information on how best to provide oral hygiene and more studies are urgently needed." ]

[ "The review authors identified four trials, with 116 participants, investigating the effectiveness of compressing therapies for PTS (most recent search 2 July 2018). Two trials studied the effect of GECS. One study showed an improvement of PTS symptoms and one showed no benefit. Two other trials studied the effect of an intermittent pneumatic compression device. Both reported an improvement in PTS severity. One study evaluated side effects and quality of life. Although 9% of the participants experienced side effects such as leg swelling, irritation, superficial bleeding, and skin itching, quality of life had positive outcomes. None of the studies assessed or reported on patient satisfaction or compliance rates. The evidence for use of GECS or intermittent pneumatic compression device compared to control for the treatment of PTS severity is of very-low and low-certainty reliability. This is due to conflicting results, small studies of short duration, and differences in how the studies measured outcomes. Limited evidence was available for side effects, patient satisfaction, quality of life, and compliance." ]

[ "This review found 81 relevant studies that recruited over 9000 participants in total. The studies mainly focussed on people having bowel surgery or caesarean section, but there were some studies of other surgery types. There were few studies of children. Most studies were of poor quality, which may mean their results are less reliable. We found some evidence that people who chewed gum after an operation were able to pass wind and have bowel movements sooner than people who did not chew gum. We also found some evidence that people who chewed gum after an operation had bowel sounds (gurgling sounds heard using a stethoscope held to the abdomen) slightly sooner than people who did not chew gum. There was a small difference in how long people stayed in hospital between people who did or did not chew gum. There were no differences in complications (such as infection or death) between people who did or did not chew gum. There was also no difference in the overall cost of treatment between people who did or did not chew gum. There is some evidence that chewing gum after surgery may help the digestive system to recover. However, the studies included in this review are generally of poor quality, which meant that their results may not be reliable. We also know that there are many factors affecting ileus, and that modern treatment plans attempt to reduce risk of ileus. Therefore to further explore using chewing gum after surgery, more studies would be needed which are larger, of better quality, include different types of surgery, and consider recent changes in health care systems." ]

[ "In this systematic review of non-randomised studies, no benefit could be demonstrated for CD over vaginal delivery (VD) in the prevention of anal incontinence. This review encompasses 21 published studies, involving 31,698 women, delivered by 6,028 CD and by 25,170 VD. No randomised studies comparing CD to VD in average risk pregnancies exist. The above conclusion is therefore based upon less than optimal evidence." ]

[ "In evidence current to September 2016, we found one trial that primarily tested if brain oxygenation can be stabilised by combining NIRS measurements of the brain with a treatment guideline on how to intervene when the brain oxygenation is outside the normal range. The 166 infants included were born more than 12 weeks before term. They were monitored during the first three days of life. The study was funded by government agency, and we found that the methods used in trial were as good as possible. The single trial we found showed a large and significant difference in brain oxygenation between the experimental group and the control group. Low oxygenation was far more common in the control group. It did not, however, find that monitoring with NIRS reduces mortality or the occurrence of the most common complications of very preterm birth, i.e. intracranial bleedings, chronic lung disease, damage of the intestines (necrotising enterocolitis), and blindness (retinopathy of prematurity). The NIRS monitoring did not cause serious harm, but skin marks from the NIRS sensor were seen in about 1 in 10 patients. The accrued information size with one small randomised trial is too small to conclude anything about the benefits and harms of cerebral near-infrared spectroscopy in preterm infants. Thus further studies are needed." ]

[ "This review is based on five randomised trials; four comparing methotrexate with placebo, and one comparing methotrexate with colchicine. Methotrexate, compared with placebo, has no significant beneficial effect on mortality and the need for liver transplantation is not significantly reduced. The effects of methotrexate on pruritus, fatigue, clinical complications, liver biochemistry levels, liver histology, and adverse events were not significantly different from placebo. There may be some beneficial effect on pruritus score (ie, an objective measure of subjective feeling of pruritus), but we cannot recommend methotrexate for this indication only, taken into account possible adverse events. In the small trial comparing methotrexate versus colchicine, methotrexate seemed to work superior to colchicine, but it is not clear if this stems from the fact that methotrexate exerts beneficial effects as colchicine exerts harmful effects. In comparison with both placebo and colchicine, methotrexate was associated with large risks of mortality and adverse events, but the increase did not reach statistical significance." ]

[ "After an extensive review of medical literature we identified three trials assessing different treatment strategies for patients with BM from SCLC. Only one of the studies compared chemotherapy (topotecan) versus no chemotherapy, but in patients treated with whole brain radiotherapy. Another study randomized patients to receive teniposide with or without brain radiation therapy, and the third one, compared sequential and concomitant chemoradiotherapy (teniposide plus cisplatin). Studies show that people who received chemotherapy did not live longer or have a longer time before the BM grew again compared to those who were treated with brain radiation therapy alone. Hematological toxicities occurred more often in patients exposed to chemoradiotherapy in one study and in patients receiving sequential treatment in another study. A major limitation of this review was the low number of included studies and participants." ]

[ "The review found some evidence that hGH does increase short-term growth in girls with TS and adult height (an increase of perhaps five centimeters or two inches). However, girls treated with hGH are still substantially shorter than other women as adults. Final height in 61 treated women was 148 cm and 141 cm in 43 untreated women." ]

[ "This evidence is current to 4 December 2015. We found 39 trials that recruited 16,082 participants testing 22 different multi-component interventions, medications or anaesthetic interventions, compared to usual care, placebo, or different interventions. We found strong evidence that multi-component interventions can prevent delirium in both medical and surgical settings and less robust evidence that they reduce the severity of delirium. Evidence about their effect on the duration of delirium is inconclusive. There is evidence that monitoring the depth of anaesthesia can reduce the occurrence of delirium after general anaesthetic. We found no clear evidence that a range of medications or other anaesthetic techniques or procedures are effective in preventing delirium. There is moderate-quality evidence to indicate that multi-component interventions reduce the incidence of delirium. The evidence supports implementing multi-component delirium prevention interventions into routine care for patients in hospital. There is moderate-quality evidence that monitoring depth of general anaesthesia can be used to prevent delirium postoperatively. The quality of the evidence for a range of medications or other anaesthetic techniques or procedures for preventing delirium is poor (because of the small number of trials and the variable quality of trial methods), and cannot be used to inform changes to practice. None." ]

[ "We searched for randomized controlled studies of immediate and early SSC on 17 December 2015. We found thirty-eight studies with 3472 women that provided data for analysis. Most studies compared early SSC with standard hospital care for women with healthy full-term babies. In eight studies women gave birth by cesarean, and in six studies the babies were healthy but born preterm at 35 weeks or more. More women who had SSC with their babies were still breastfeeding at one to four months after giving birth (14 studies, 887 women, moderate-quality evidence). Mothers who had SSC breast fed their infants longer, too, on average over 60 days longer (six studies, 264 women, low-quality evidence). Babies held in SSC were more likely to have breast fed successfully during their first breast feed (five studies, 575 women). Babies held in SSC had higher blood glucose levels (three studies, 144 women, low-quality evidence), but similar temperature to babies with standard care (six studies, 558 women, low-quality evidence). We had too few babies in our included studies and the quality of the evidence was too low for us to be very confident in the results for infants. Women giving birth by cesarean may benefit from early SSC, with more women breastfeeding successfully and still breastfeeding at one to four months (fourteen studies, 887 women, moderate-quality evidence), but there were not enough women studied for us to be confident in this result. We found no clear benefit to immediate SSC rather than SSC after the baby had been washed and examined. Neither did we find any clear advantage of a longer duration of SSC (more than one hour) compared with less than one hour. Future trials with more women and infants may help us answer these questions with confidence. SSC was defined in various ways and different scales and times were used to measure different outcomes. Women and staff knew they were being studied, and women in the standard care groups had varying levels of breastfeeding support. These differences lead to wide variation in the findings and a lower quality evidence. Many studies were small with less than 100 women participating. The evidence from this updated review supports using immediate or early SSC to promote breastfeeding. This is important because we know breastfeeding helps babies avoid illness and stay healthy. Women giving birth by cesarean may benefit from early SSC but we need more studies to confirm this. We still do not know whether early SSC for healthy infants helps them make the transition to the outside world more smoothly after birth, but future good quality studies may improve our understanding. Despite our concerns about the quality of the studies, and since we found no evidence of harm in any included studies, we conclude the evidence supports that early SSC should be normal practice for healthy newborns including those born by cesarean and babies born early at 35 weeks or more." ]

[ "We wanted to know whether any treatments were successful in improving pain, and reducing disability and distress in survivors of torture. We searched the academic literature to February 2017 and found three randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups). Two studies (58 participants) compared cognitive behavioural therapy (CBT; talking therapy that helps people change the way they think and behave) plus learning to control muscles and breathing with no treatment, and we were able to combine these for analysis. Neither study showed any meaningful improvement in pain, reduction in disability, or reduction in distress, over eight to 13 weeks of treatment. One study (30 participants) compared complex manual therapy with self-treatment for low back pain but could not be combined with the other two studies; it reported no difference in pain relief, but did report that the physical intervention reduced disability and distress at the end of treatment. 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. The quality of the evidence was very low for pain relief, reduction in distress, and reduction in disability. This was due to the small size of the studies, poor study design, and substantial dropout of participants from studies." ]

[ "In this updated review, we identified 10 studies involving a total of 1015 participants. We did not find any well-designed randomized controlled trial evidence to support the use of these medications. Trials of antioxidants identified in this review were generally of poor methodological quality and lacked statistical power. However, antioxidants are generally well tolerated without serious adverse effects." ]

[ "This review examines the benefits and costs of outreach in a range of specialties and in a variety of settings. Simple 'shifted outpatients' styles of specialist outreach were shown to improve access, but there was no evidence of their impact on health outcomes. Outreach as part of more complex multifaceted interventions involving primary care collaborations, education and other services was associated with improved health outcomes, more efficient and guideline-consistent care, and less use of inpatient services. There is a need for better quality evidence evaluating specialist outreach in all settings, but especially in rural and disadvantaged populations." ]

[ "We searched scientific databases for studies comparing NCPAP versus NIPPV in preterm infants (born before 37 completed weeks of pregnancy) who no longer need an endotracheal tube. We looked at breathing problems, the need for the endotracheal tube to be re-instated and side effects. Evidence is current to September 2015. We found ten trials comparing NCPAP versus NIPPV. Six of ten studies that compared NCPAP and NIPPV showed that NIPPV reduced the need for re-insertion of the endotracheal tube. Future studies must determine how NIPPV can best be delivered to infants. In clinical trials, clinicians and investigators were aware of the intervention received by each infant (NIPPV or NCPAP). Therefore, we graded the quality of evidence for the primary outcome (breathing problems and need for re-insertion of the endotracheal tube) as moderate." ]

[ "We found four studies that randomly allocated 389 patients to receive ECMO versus conventional lung support. All studies comprised patients with acute lung failure. We found no completed study in patients with acute heart failure or arrest. We found one ongoing study in patients with acute lung failure and two ongoing studies in patients with acute heart failure (arrest). The evidence is current to August 2014. Clinical differences in the care provided for patients with acute lung failure prevented us from combining the results of individual studies. Individual studies reported no differences in all-cause death at or before six months in patients given ECMO compared with those who were not. In one study survival was low in both groups but none of the patients who survived had limitations in their daily activities six months after discharge. Another study found improved survival without severe disability in patients transferred to an ECMO centre for consideration of ECMO six months after study entry. In three studies, patients in the ECMO group received greater numbers of blood transfusions. One study reported more non-brain bleeding in the ECMO group, and another study reported two serious adverse events in the ECMO group. Another study reported three adverse events in the ECMO group. Clinical practice, study planning and ways of using ECMO have varied considerably among studies. Technological developments (circuits, pumps and mechanical lungs) have improved performance and patient safety with ECMO applications over time. These clinical differences in the care provided for patients with acute lung failure prevented us from combining the results of individual studies. In critically ill adults, ECMO may or may not be more effective in improving survival compared with conventional lung support. Results from ongoing studies will help us better understand the role of ECMO and ECPR in the treatment of patients with acute lung or heart failure." ]

[ "The evidence on which this review is based is up to date as of 15 May 2018. We found six relevant articles to include in this review. All are related to one single study conducted in Hong Kong between 2002 and 2008. The study involved 47 participants aged 13 to 45 years of age. It investigated the effects of the two surgical procedures on alteration of face morphology, stability of upper jaw after surgery, speech and velopharyngeal function (ability to close the gap between the soft palate and nasal cavity to produce sound), psychological status of the participants and clinical side effects. Both procedures were effective in producing better facial structure in cleft patients. Upper jaw was more stable in the distraction osteogenesis group than the conventional osteotomy group five years after surgery. There was no difference in speech and velopharyngeal function between the procedures. Social self esteem in the maxillary distraction group initially seemed to be lower than in the conventional surgery group, but this improved over time and the distraction group had higher satisfaction with life two years after surgery. Side effects included deterioration of the fit between the teeth when the mouth is closed and infection of muscous membranes of the nose and mouth, but the frequency of these problems was similar between groups. There was no severe harm to any participant. We judged the quality of the evidence to be very low. The one study was small and there were concerns about aspects of its design and reporting; therefore we have found no reliable evidence as to which procedure should be regarded superior. High quality clinical trials, which involve lots of people, and different face types, are required to guide decision making." ]

[ "Six trials which investigated the effect of ketanserin on 146 patients with either primary Raynaud's phenomenon or Raynaud's phenomenon secondary to systemic sclerosis were included (Cadranel 1986; Dormandy 1988; Kirch 1987; Lukac 1985; Ortonne 1989; van de Wal 1987). Patients treated with ketanserin experienced a greater improvement in mean functional index scores and more patients improved than those treated with placebo, however they also experienced more side effects and an increase in the frequency and duration of attacks. This review assessed a limited number of studies and therefore the conclusions reached need to be investigated further." ]

[ "We searched for scientific research studies known as 'randomised controlled trials', up to 17 September 2019. In this type of study, participants are assigned in a random way to an experimental or control group. People in the experimental group receive the treatment being tested, and people in the control group usually receive either no treatment, placebo (fake treatment), another type of treatment or routine care. We found two studies to include in our review. One study assessed 165 participants who did not have cardiovascular diseases, but had metabolic syndrome (a combination of risk factors for cardiovascular disease, such as obesity, high blood pressure, and high blood sugar). The other study started off with 303 participants who had cardiovascular diseases, but after a year, only 37 participants were assessed and so we thought the results were not be reliable enough to be used. Both studies had problems with their design, and we judged them to be at high risk of bias. For people who have metabolic syndrome but no cardiovascular diseases, we were unable to determine whether treating chronic periodontitis, by removing the plaque and tartar ('scaling') from the roots of teeth and giving antibiotics, reduced the risk of dying or having cardiovascular attacks when compared with scaling the teeth from above the gumline only. For people with cardiovascular diseases and chronic periodontitis, we found no reliable evidence about the effects of periodontal treatment. We classified the evidence as 'very low certainty'. We are uncertain about the findings because there are only two small studies, at high risk of bias, with very imprecise results. Overall, we cannot draw any reliable conclusions from the findings. Further research is needed." ]

[ "We found 30 trials involving 4691 participants, examining several types of contracts. The main health problems targeted were substance addictions, hypertension and overweight. Many of the trials were of poor quality and involved small numbers of people. Most were conducted in the USA. In 15 of the trials there was at least one outcome showing statistically significant differences in favour of the contracts group (although some of the improvements in adherence did not remain when measured after a longer period). In six trials at least one outcome showed such differences in favour of the control group. In 26 trials there was at least one outcome for which there was no difference between the contract and control groups. There is not enough reliable evidence available to recommend the routine use of contracts in health services to improve patients' adherence to healthcare activities or other outcomes." ]

[ "Following meticulous searches of major databases (all databases searched June 2013, MDSG register last searched June 2014) and conference proceedings we were able to locate four trials, with a total of 1392 women. These were all prospective, randomised controlled trials comparing two competing post-ET interventions or an intervention versus no treatment on clinical outcomes in women undergoing IVF and ICSI. Each study recruited from 164 to 639 infertile women of reproductive age and all were conducted in IVF centres; none of them had conflicts of interest regarding study funding. Our primary measure of success, live birth rate, was not reported in any of the included trials. There was insufficient evidence to support a specific length of time for women to remain recumbent, if at all, following ET, nor was there sufficient evidence to recommend the use of fibrin sealants. There was very limited evidence to support the use of mechanical pressure to close the cervical canal. Further large well-designed studies are required to determine the true effectiveness and safety of these interventions. There was no evidence that any of the interventions had an effect on adverse event rates, but data were too few to reach any conclusions. The quality of the evidence was low or very low for all comparisons. The main limitations were failure to report live births, imprecision and risk of bias. Study risk of bias was variable, with the reporting of a proper method of randomisation and allocation concealment demonstrated in most trials while only one trial clearly blinded both the patients and the clinicians to the intervention received." ]

[ "Herbal preparations are commonly used alternatives to drug treatment, surgery, or both. This systematic review included 21 randomised clinical trials involving 2222 women with uterine fibroids. There is no evidence on the effectiveness of herbal preparations for symptom relief as no trials evaluated this properly. Compared with conventional medication, one herbal preparation, Tripterygium wilfordii, may have a more beneficial effect in reducing the volume of uterine fibroids. Another five herbal medicines appeared to be similar to conventional medication in reducing the volume of fibroids. The herbal medicine Guizhi Fuling formula showed a significantly greater effect in reducing the volume of the fibroids when combined with mifepristone versus mifepristone alone. However, these clinical trials were small in terms of the number of participants and the trial quality was low. Thirteen out of 21 included trials reported on adverse effects of herbal preparations and found some minor problems such as stomach discomfort, nausea, hot flushes, and poor appetite although no serious adverse effects were identified. The effect of herbal preparations for uterine fibroids is therefore not confirmed in this review and needs to be studied in large, good quality trials." ]