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We identified eight RCTs involving 805 participants. Two trials comparing COCP with placebo were considered to be moderate quality and the remaining studies were low to very low quality, mainly because of serious risk of bias from lack of blinding and concerns over precision. COCP versus placebo COCP, with a step-down oestrogen and step-up progestogen regimen, improved response to treatment (return to menstrual 'normality') (OR 22.12, 95% CI 4.40 to 111.12; 2 trials; 363 participants; I2 = 50%; moderate-quality evidence), and lowered MBL (OR 5.15, 95% CI 3.16 to 8.40; 2 trials; 339 participants; I2 = 0%; moderate-quality evidence) when compared to placebo. The results suggested that, if the chance of 'successful' treatment was 3% in women taking placebo, then COCP increased this chance from 12% to 77% in women with unacceptable HMB. Minor adverse events, in particular breast pain, were more common with COCP. No study in this comparison reported semi-objectively assessed MBL or participant satisfaction with treatment. COCP versus other medical treatments Non-steroidal anti-inflammatory drugs (NSAIDs) There was insufficient evidence to determine whether the COCP reduced MBL when compared to NSAIDs (mefenamic acid and naproxen). No study in this comparison reported semi-objectively assessed MBL, subjectively assessed MBL, participant satisfaction with treatment or adverse events. Levonorgestrel-releasing intrauterine system (LNG IUS) The LNG IUS was more effective than COCP in reducing MBL (OR 0.21, 95% CI 0.09 to 0.48; 2 trials; 151 participants; I2 = 0%; low-quality evidence) but it was not clear whether satisfaction with treatment or adverse effects varied according to which treatment was used. No study in this comparison reported semi-objectively assessed MBL or subjectively assessed MBL. Contraceptive vaginal ring (CVR) versus other medical treatments COCP COCP was compared with CVR in two trials. There were discrepancies between some of the findings and there was no evidence of a benefit for one treatment compared to the other for response to treatment, MBL or participant satisfaction with treatment. There was a greater likelihood of nausea with COCP. No study in this comparison reported objectively assessed MBL or subjectively assessed MBL. Progestogens CVR was compared to long course progestogens in one trial. It is possible that CVR increased the odds of satisfaction; but we are uncertain whether CVR improved MBL. The evidence was based on small numbers of participants and was very low quality, so definitive conclusions could not be reached. No study in this comparison reported objectively assessed MBL, subjectively assessed MBL, or adverse events. Moderate-quality evidence suggests that the combined oral contraceptive pill over six months reduces HMB in women with unacceptable HMB from 12% to 77% (compared to 3% in women taking placebo). When compared with other medical options for HMB, COCP was less effective than the LNG IUS. Limited evidence suggested that COCP and CVR had similar effects. There was insufficient evidence to determine comparative efficacy of combined hormonal contraceptives with NSAIDs, or long course progestogens. | Eight studies, which included 805 women, were identified that compared combined hormonal contraceptives (mostly, the combined contraceptive pill) with either no treatment, placebo or other medical treatments. The studies assessed the effects of interventions on menstrual bleeding, satisfaction, quality of life, adverse events, and haemoglobin levels (protein in red blood cells that carries oxygen throughout the body). The evidence is current to September 2018. Two studies found that a type of COCP, containing estradiol valerate and dienogest, reduced HMB and improved quality of life and haemoglobin levels when compared with placebo, but at the expense of some minor side effects. There was insufficient evidence to compare contraceptives with other treatments, such as nonsteroidal anti-inflammatories or progestogens. Two studies found that the levonorgestrel-releasing intrauterine system (LNG IUS) was more effective than the COCP at reducing menstrual blood loss. Two trials found no evidence of different effects between the oral contraceptive pill or the hormonal vaginal ring. We found no studies that assessed the effects of the combined hormonal patch (transdermal patch). The quality of the evidence that compared the oral contraceptive pill with placebo was moderate, but the evidence for the other comparisons was either low or very low in quality. The LNG IUS is more effective than the COCP at reducing menstrual bleeding but evidence was insufficient for the other treatment comparisons. This means that, although it is likely that combined hormonal contraceptives can reduce HMB, we cannot be absolutely certain how they compare with other medical treatments for reducing HMB (although LNG IUS appears to be more effective). |
Three cross-over studies, with 175 women were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor. Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50) The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined. The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002). In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34). Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported. Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison. When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin. There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated. | The review included three studies on non-surgical treatments in 175 women with a bleeding disorder who were experiencing heavy menstrual bleeding. Twostudies compared desmopressin to placebo and one study compared desmopressin to tranexamic acid. The women included in the studies were selected for one treatment or the other randomly. The studies lasted from two to four months. Two studies of the three studies (with a total of 59 women) found no clear evidence of a difference in desmopressin (1-deamino-8-D-arginine vasopressin) in reducing menstrual blood loss when compared to placebo. One of these studies continued with an open non-randomised comparison of a combination of desmopressin with tranexamic acid versus placebo and found a significant reduction in menstrual blood loss. However, the non-randomised design of this comparison is an additional potential source of bias. The third study (116 women), which had more participants than the other two studies combined, found a greater reduction in menstrual blood loss with tranexamic acid use than with desmopressin. We were unable to present any data on quality of life from this study, since no differences in between the two intervention groups were reported. There was no clear evidence of difference in the risk of side effects with desmopressin as compared to tranexamic acid. None of the studies dealt with cost effectiveness. We were not able to adequately assess the studies in relation to how the women were allocated to the treatment groups and we judged the overall quality of the evidence as poor. |
We included three randomised controlled trials involving 212 participants. The evidence available does not demonstrate that FESS, as practised in the included trials, is superior to medical treatment with or without sinus irrigation in patients with chronic rhinosinusitis. A middle meatal antrostomy fashioned by FESS was also not shown to be superior to an inferior meatal antrostomy formed by traditional sinus surgery techniques, although the small sample size in the study does not exclude a type II error. In one study there was a relapse rate of 2.4% in the FESS and sinus irrigation group compared to 5.6% in the sinus irrigation only group. The relapse rates were not mentioned in the other studies. There were no major complications, such as orbital injury or cerebrospinal fluid leak, reported in any of the included trials. FESS as currently practised is a safe surgical procedure. The limited evidence available suggests that FESS as practised in the included trials has not been demonstrated to confer additional benefit to that obtained by medical treatment (+/- sinus irrigation) in chronic rhinosinusitis. More randomised controlled trials comparing FESS with medical and other treatments, with long-term follow up, are required. | Three randomised controlled trials, involving 212 participants, met the inclusion criteria for this review. The evidence available does not demonstrate that FESS, as practised in the included trials, is superior to medical treatment with or without sinus irrigation in patients with chronic rhinosinusitis. There were no major complications in any of the included trials and FESS appears to be a safe procedure. More randomised controlled trials comparing FESS with medical and other treatments, with long-term follow up, are required. |
One hundred thirty-seven studies involving 8333 eyes met the inclusion criteria. Placebo-controlled studies were heterogeneous in comparison with idoxuridine (RR 1.74; 95% CI 1.03 to 2.91) and few in number for vidarabine (RR 1.81; 95% CI 1.09 to 3.01), interferon (RR 1.32; 95% CI 1.06 to 1.64), and debridement. Vidarabine (RR 1.13; 95% CI 1.02 to 1.25), trifluridine (RR 1.30; 95% CI 1.18 to 1.43), acyclovir (RR 1.23; 95% CI 1.14 to 1.34), and brivudine (RR 1.34; 95% CI 1.18 to 1.51) were more effective than idoxuridine. Trifluridine (RR 1.17; 95% CI 1.03 to 1.32) and acyclovir (RR 1.11; 95% CI 1.03 to 1.19) were more effective than vidarabine. No significant differences in healing emerged among trifluridine, acyclovir, brivudine, and foscarnet although few studies compared brivudine or foscarnet with other antivirals. Any potential advantage of ganciclovir compared to acyclovir was mitigated by study heterogeneity and possible publication bias. Only one study evaluated the joint use of two topical antivirals. In a limited number of studies, oral acyclovir (RR 0.92; 95% CI 0.79 to 1.07) or the combination of oral acyclovir with a topical antiviral (RR 1.36; 95% CI 0.68 to 2.74) appeared as effective as a single topical antiviral agent. Compared to topical antiviral monotherapy, the combination of an antiviral with either interferon or debridement had inconsistent effects on expediting healing and improving outcome. Placebo-controlled studies of HSV epithelial keratitis are limited to superseded interventions. Trifluridine and acyclovir are more effective than idoxuridine or vidarabine and similar in therapeutic effectiveness. Brivudine and foscarnet do not substantially differ in effectiveness from trifluridine or acyclovir. Ganciclovir is at least as effective as acyclovir. The addition of interferon to a nucleoside antiviral agent and the combination of debridement with antiviral treatment need to be further assessed to substantiate any possible advantage in healing. | This update, current to December 2014, uses a network of 137 studies of 8333 eyes to compare antiviral medicines and to find out if interferon or debridement would help. Between one and 28 studies were available to compare seven ophthalmic antiviral drugs, an antiviral taken by mouth, interferon, office procedures to remove the eye's infected surface, and other medicines. The first antivirals, idoxuridine and vidarabine, seem better than no treatment in healing HSV dendritic keratitis within two weeks. Topically applied trifluridine, acyclovir, or brivudine are better and safer than idoxuridine, cure about 90% of treated eyes within two weeks, and have no significant differences in effectiveness. The evidence is conflicting whether ganciclovir is as good as or better than acyclovir. Determining the role of antiviral pills is limited by few studies and inconsistent findings. Interferon, a natural part of the immune system that can be given as an eye drop, is active against HSV infection of the cornea. The integrated use of interferon and an antiviral drug might be slightly better than an antiviral drug by itself. Another treatment is to rub off the infected surface of the eye, but using a wiping method followed by an antiviral drug is not consistently better than just an antiviral medication. Comparisons of one ophthalmic antiviral drug to another have a moderate quality of evidence, except for the appraisal comparing ganciclovir and acyclovir where studies are inconsistent. The quality of the evidence is moderate to low when an ophthalmic antiviral drug was compared to combined antiviral and interferon treatments or to combined antiviral treatment and debridement. Evidence is scarce or poor for placebo-controlled comparisons, comparisons of antiviral treatment to interferon or to debridement, and evaluations of antiviral pills. Proper randomisation could not be assured in nearly a quarter of the studies. Patients or examiners could have known which treatment was assigned in at least half of the studies. |
The results of twenty-five studies were used in the meta-analysis. The results suggest that speech and language therapy is effective for children with phonological (SMD=0.44, 95%CI: 0.01,0.86) or vocabulary difficulties (SMD=0.89, 95%CI: 0.21,1.56), but that there is less evidence that interventions are effective for children with receptive difficulties (SMD=-0.04, 95%CI: -0.64,0.56). Mixed findings were found concerning the effectiveness of expressive syntax interventions (n=233; SMD=1.02, 95%CI: 0.04-2.01). No significant differences were shown between clinician administered intervention and intervention implemented by trained parents, and studies did not show a difference between the effects of group and individual interventions (SMD=0.01, 95%CI: -0.26,1.17). The use of normal language peers in therapy was shown to have a positive effect on therapy outcome (SMD=2.29, 95%CI: 1.11,3.48). The review shows that overall there is a positive effect of speech and language therapy interventions for children with expressive phonological and expressive vocabulary difficulties. The evidence for expressive syntax difficulties is more mixed, and there is a need for further research to investigate intervention for receptive language difficulties. There is a large degree of heterogeneity in the results, and the sources of this need to be investigated. | This review examines the effectiveness of speech and language therapy interventions for children with primary speech and language delay/disorder.The review concludes that whilst there may be some support for the effectiveness of speech and language therapy for children with expressive phonological and expressive vocabulary difficulties, the evidence concerning the effectiveness of interventions for expressive syntax is mixed, and no evidence is available concerning interventions for children with receptive language difficulties. |
We included three studies which randomised women (1099) with a body mass index (BMI) of 30 kg/m2 (1 study) and 35 kg/m2 (2 studies), with outcomes available for 1034 participants. None of the studies assessed women with a BMI between 25 kg/m2and 29.9 kg/m2, therefore we could not assess the use of metformin in women considered overweight. We did not identify studies of metformin in combination with another treatment. Two other studies are ongoing. All three included studies were randomised controlled trials and compared metformin with placebo, commencing early in the second trimester. Doses ranged from 500 mg twice daily to 3.0 g per day. All three studies (two in the UK, one in Egypt) included women attending hospitals for antenatal care. Two studies were generally at a low risk of bias across the majority of domains. We assessed the third study as being at an unclear risk of selection bias, performance and detection bias due to insufficient information in the report. We assessed the trial as being at a low risk of attrition bias and other bias; we felt it was at a high risk of reporting bias. The primary outcome for this review was infant birthweight large-for-gestational-age (> 90th centile for gestational age and infant sex). Women who received metformin or placebo had a similar risk of their baby being born large for his or her gestational age (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.30; 2 studies, 831 infants; high-quality evidence). Women who received metformin may have a slightly lower gestational weight gain (mean difference (MD) -2.60 kg, 95% CI -5.29 to 0.10; 3 studies, 899 women; low-quality evidence). Metformin may make little or no difference in the risk of women developing gestational hypertension (average RR 1.02, 95% CI 0.54 to 1.94; 3 studies, 1040 women; low-quality evidence) or pre-eclampsia (RR 0.74, 95% CI 0.09 to 6.28; 2 studies, 840 women; low-quality evidence). Metformin probably makes little or no difference in the risk of women developing gestational diabetes (RR 0.85, 95% CI 0.61 to 1.19; 3 studies, 892 women; moderate-quality evidence). One study of 400 women reported women receiving metformin were more likely to experience any adverse effect compared with women receiving placebo (RR 1.63, 95% CI 1.27 to 2.08; 1 study, 400 women). Adverse effects included abdominal pain, diarrhoea, or headache. When considering individual side effects, women receiving metformin were more likely to experience diarrhoea than women receiving placebo (RR 2.34, 95% CI 1.74 to 3.14; 797 women; 2 studies, 797 women; high-quality evidence). No other important differences were identified between Metformin and placebo for other maternal secondary outcomes, including: caesarean birth, birth before 37 weeks of pregnancy, shoulder dystocia, perineal tear, or postpartum haemorrhage. In terms of other infant outcomes, there was little or no difference in the infant birthweight (MD 6.39 g, 95% CI -81.15 to 93.92; 2 studies, 834 infants; high-quality evidence). There were no other important differences identified for other infant secondary outcomes in this review: hypoglycaemia (low blood sugar); hyperbilirubinaemia (jaundice); Apgar score less than 7 at five minutes; or stillbirth and neonatal death. Only one study reported admission to the neonatal intensive care unit (NICU), indicating similar rates of admission between women receiving metformin or placebo; no other admission data were reported to assess differences in costs. There is insufficient evidence to support the use of metformin for women with obesity in pregnancy for improving maternal and infant outcomes. Metformin was, however, associated with increased risk of adverse effects, particularly diarrhoea. The quality of the evidence in this review varied from high to low, with downgrading decisions based on study limitations and inconsistency. There were only a small number of studies included in this review. Furthermore, none of the included studies included women categorised as 'overweight' and no trials looked at metformin in combination with another treatment. Future research is required in order to further evaluate the role of metformin therapy in pregnant women with obesity or who are overweight, as a strategy to improve maternal and infant health, alone or as an adjuvant to dietary and lifestyle advice. | We searched for evidence (October 2017) and found three randomised controlled studies (1099 pregnant women) comparing metformin tablets with placebo (dummy) tablets taken by mouth from 10 to 20 weeks of pregnancy until birth. The studies involved women with obesity; we therefore could not assess the effect of metformin in women who are overweight. Women who were given metformin or placebo during pregnancy had a similar risk of a baby being born large-for-gestational age (measured in weeks since last period). Metformin probably makes little or no difference in the risk of women developing gestational diabetes. Metformin may also have little or no difference in the risk of women developing gestational hypertension (high blood pressure) or pre-eclampsia. Women who were given metformin may gain slightly less weight during pregnancy, but are more likely to experience diarrhoea. There were no other important differences identified for other maternal outcomes including, caesarean birth, giving birth before 37 weeks of pregnancy, shoulder dystocia (a birth complication where the baby’s shoulder gets stuck), perineal trauma (damage to the area between the woman’s vagina and the anus), or heavy bleeding after the baby has been born. Babies of women who were given metformin had similar birthweight to babies of women who were given placebo. We did not identify any other important differences for other infant outcomes of interest: hypoglycaemia (low blood sugar); hyperbilirubinaemia (jaundice); Apgar score at five minutes (a measure of newborn well-being); or death of the baby before or after being born. One study reported similar rates of admission to neonatal intensive care between groups. There is insufficient evidence to support the use of metformin for women with obesity in pregnancy for improving outcomes for the mother and her baby. Metform was associated with increased risk of adverse effects, particularly diarrhoea. A small number of studies are included in this review and no study included women categorised as 'overweight', or looked at metformin in combination with another treatment. More research is needed to evaluate the role of metformin in pregnant women with obesity or who are overweight, as a strategy for improving maternal and infant health, either alone or as an additional intervention. |
We identified 18 RCTs examining a range of complex interventions for people with multimorbidity. Nine studies focused on defined comorbid conditions with an emphasis on depression, diabetes and cardiovascular disease. The remaining studies focused on multimorbidity, generally in older people. In 12 studies, the predominant intervention element was a change to the organisation of care delivery, usually through case management or enhanced multidisciplinary team work. In six studies, the interventions were predominantly patient-oriented, for example, educational or self-management support-type interventions delivered directly to participants. Overall our confidence in the results regarding the effectiveness of interventions ranged from low to high certainty. There was little or no difference in clinical outcomes (based on moderate certainty evidence). Mental health outcomes improved (based on high certainty evidence) and there were modest reductions in mean depression scores for the comorbidity studies that targeted participants with depression (standardized mean difference (SMD) −2.23, 95% confidence interval (CI) −2.52 to −1.95). There was probably a small improvement in patient-reported outcomes (moderate certainty evidence) although two studies that specifically targeted functional difficulties in participants had positive effects on functional outcomes with one of these studies also reporting a reduction in mortality at four year follow-up (Int 6%, Con 13%, absolute difference 7%). The intervention may make little or no difference to health service use (low certainty evidence), may slightly improve medication adherence (low certainty evidence), probably slightly improves patient-related health behaviours (moderate certainty evidence), and probably improves provider behaviour in terms of prescribing behaviour and quality of care (moderate certainty evidence). Cost data were limited. This review identifies the emerging evidence to support policy for the management of people with multimorbidity and common comorbidities in primary care and community settings. There are remaining uncertainties about the effectiveness of interventions for people with multimorbidity in general due to the relatively small number of RCTs conducted in this area to date, with mixed findings overall. It is possible that the findings may change with the inclusion of large ongoing well-organised trials in future updates. The results suggest an improvement in health outcomes if interventions can be targeted at risk factors such as depression, or specific functional difficulties in people with multimorbidity. | We searched the literature up to September 2015 and identified 18 generally well-designed randomised controlled trials meeting the eligibility criteria. Nine of these studies focused on specific combinations of health conditions (comorbidity studies), for example diabetes and heart disease. The other nine studies included people with a broad range of conditions (multimorbidity studies) although they tended to focus on elderly people. The majority of studies examined interventions that involved changes to the organisation of care delivery although some studies had more patient-focused interventions. All studies had governmental or charitable sources of funding. Overall the results regarding the effectiveness of interventions were mixed. There were no clear positive improvements in clinical outcomes, health service use, medication adherence, patient-related health behaviours, health professional behaviours or costs. There were modest improvements in mental health outcomes from seven studies that targeted people with depression, and in functional outcomes from two studies targeting functional difficulties in participants. Overall the results indicate that it is difficult to improve outcomes for people with multiple conditions. The review suggests that interventions that are designed to target specific risk factors (for example treatment for depression) or interventions that focus on difficulties that people experience with daily functioning (for example, physiotherapy treatment to improve capacity for physical activity) may be more effective. There is a need for further studies on this topic, particularly involving people with multimorbidity in general across the age ranges. All of the included studies were randomised controlled trials. The overall quality of these studies was good though many studies did not fully report on all potential sources of bias. As definitions of multimorbidity vary among studies, the potential to reasonably combine study results and draw overall conclusions is limited. Overall, we judged that the certainty or confidence we can have in the results from this review is moderate but due to small numbers of studies and mixed results we acknowledge the uncertainty remaining and the potential that future studies could change our conclusions. |
Forty-two studies were included in the review. There was evidence that MHWs caused significant reductions in PCP consultations (standardised mean difference -0.17, 95% CI -0.30 to -0.05), psychotropic prescribing (relative risk 0.67, 95% CI 0.56 to 0.79), prescribing costs (standardised mean difference -0.22, 95% CI -0.38 to -0.07), and rates of mental health referral (relative risk 0.13, 95% CI 0.09 to 0.20) for the patients they were seeing. In controlled before and after studies, the addition of MHWs to a practice did not affect prescribing behaviour towards the wider practice population and there was no consistent pattern to the impact on referrals in the wider patient population. This review provides some evidence that MHWs working in primary care to deliver psychological therapy and psychosocial interventions cause a significant reduction in PCP behaviours such as consultations, prescribing, and referrals to specialist care. However, the changes are modest in magnitude, inconsistent, do not generalise to the wider patient population, and their clinical or economic significance is unclear. | This review investigated whether having mental health workers on-site to work with physicians at their offices would change the care that physicians provide. Forty-two studies were reviewed in which on-site mental health workers, such as counsellors or psychiatrists, worked alongside physicians to provide therapy to patients. The review found that when there were mental health workers on-site, patients may reduce the number of visits to their doctors; doctors may reduce how often they refer patients to off-site mental health specialists; doctors may reduce the number of drugs they prescribe to the patients who see the mental health workers; and the costs related to those drugs may be lower. However, these reductions were small and not found consistently in all the studies. The review also found that there may be little or no difference in how the doctors prescribe drugs or refer patients who have mental health problems but are not seeing the on-site mental health workers. It is also not known what the effect of on-site mental health workers had on how well physicians recognised and diagnosed mental health problems. |
We identified 18 eligible primary publications (21 trial reports). A total of 3089 infants participated in the trials. The risk of bias varied with lack of clarity on methods to conceal allocation in half of the trials and lack of blinding of caregivers or investigators in all of the trials being the main potential sources of bias. Eight trials (2086 infants) examined the effect of topical ointments or creams. Most participants were very preterm infants cared for in health-care facilities in high-income countries. Meta-analyses did not show evidence of a difference in the incidence of invasive infection (typical risk ratio (RR) 1.13, 95% confidence interval (CI) 0.97 to 1.31; low quality evidence) or mortality (typical RR 0.87, 95% CI 0.75 to 1.03; low quality evidence). Eleven trials (1184 infants) assessed the effect of plant or vegetable oils. Nine of these trials were undertaken in low- or middle-income countries and all were based in health-care facilities rather than home or community settings. Meta-analyses did not show evidence of a difference in the incidence of invasive infection (typical RR 0.71, 95% CI 0.51 to 1.01; low quality evidence) or mortality (typical RR 0.94, 95% CI 0.81 to 1.08; moderate quality evidence). Infants massaged with vegetable oil had a higher rate of weight gain (about 2.55 g/kg/day; 95% CI 1.76 to 3.34), linear growth (about 1.22 mm/week; 95% CI 1.01 to 1.44), and head growth (about 0.45 mm/week; 95% CI 0.19 to 0.70). These meta-analyses contained substantial heterogeneity. The available data do not provide evidence that the use of emollient therapy prevents invasive infection or death in preterm infants in high-, middle- or low-income settings. Some evidence of an effect of topical vegetable oils on neonatal growth exists but this should be interpreted with caution because lack of blinding may have introduced caregiver or assessment biases. Since these interventions are low cost, readily accessible, and generally acceptable, further randomised controlled trials, particularly in both community- and health care facility-based settings in low-income countries, may be justified. | Study characteristics: Our search (August 2015) identified 21 eligible trial reports (in 18 primary publications). In total, 3089 infants participated. Eight trials (2086 infants) examined the effect of topical ointments or creams. Most participants were very preterm infants cared for in health-care facilities in high-income countries. Eleven trials (1184 infants) assessed the effect of sunflower, sunflower seed, and other vegetable oils. Nine of these trials were undertaken in low- or middle-income countries and all were based in health-care facilities rather than home or community settings. Results: Analyses of these trial data provided low quality evidence and did not show that emollients prevent infection or death in preterm infants. Conclusions: These analyses do not provide evidence that the use of emollient therapy prevents invasive infection or death in preterm infants in high-, middle- or low-income countries. Since these interventions are low cost, readily accessible and generally acceptable, further randomised controlled trials, particularly in both community- and health care facility-based settings in low-income countries, may be justified. |
We included three randomised controlled trials, involving a total of 251 participants. All three trials were at high risk of performance bias reflecting the fact that surgeons could not be blinded. One trial was at low risk of selection bias but was undermined by a high attrition bias, in part resulting from post-randomisation exclusions. There were incomplete details of methodology for the other two trials, which usually resulted in unclear risk of bias judgements. Two trials compared radial head replacement with open reduction and internal fixation (ORIF) for treating Mason type III radial head fractures. The trial authors reported outcomes at a mean of 2.8 years and 15 months respectively. There were significant differences between the two groups in favour of radial head replacement in the Broberg and Morrey elbow scores (92.1 versus 72.4, mean difference (MD) 19.70; 95% confidence interval (CI) 15.64 to 23.76; one trial, 45 participants), excellent or good Broberg and Morrey elbow scores (33/36 versus 16/31, risk ratio (RR) 1.88; 95% CI 1.27 to 2.77; two trials), and overall adverse events (6/36 versus 15/31, RR 0.33; 95% CI 0.14 to 0.77; two trials). No statistically significant difference was found between the two groups in any of the reported individual adverse events. One trial compared biodegradable pins with standard metal screws in treating radial head fractures of AO-classification 21 B2. The two types of fixation devices yielded similar results, with no significant between-group differences in the Broberg and Morrey scores (93.3 versus 90.9, MD 2.40; 95% CI -0.10 to 4.90), excellent or good Broberg and Morrey elbow scores (72/74 versus 56/61, RR 1.06; 95% CI 0.97 to 1.15), and adverse events (13/82 versus 16/82, RR 0.81; 95% CI 0.42 to 1.58) at two-year follow-up. Only tentative conclusions can be drawn from the available evidence in this review. Compared with ORIF, there was some evidence that radial head replacement had better elbow function and fewer adverse events for Mason type III radial head fractures in the short term. However, the evidence is of low quality and it is unknown whether these results would apply in the longer term or more generally. Using biodegradable implants may be as good as metallic implants for fixation of some usually more stable fractures but more evidence is needed to confirm this. There is a need for good quality evidence for addressing the areas of uncertainty for the surgical treatment of radial head fractures. | This review includes evidence from three randomised controlled trials with a total of 251 participants. All three trials were at some risk of bias, which means that their results may not be reliable. Two trials compared radial head replacement with ORIF for treating highly fragmented radial head fractures. These trials showed that after radial head replacement, patients had significantly better elbow function and fewer adverse events than those treated with ORIF at between one and three years follow-up. One trial compared biodegradable pins with standard metal screws in treating displaced radial head fractures. It found similar results for the two types of materials in terms of elbow function and adverse events. Overall, there is some evidence to support radial head replacement for treating highly fragmented radial head fractures instead of attempting to fix the fractured bone back in place. However, the evidence is low quality and it is unknown whether these results would apply in the longer term or more generally. Using biodegradable implants may be as good as metallic implants for fixing some usually more stable fractures but more evidence is needed to confirm this. |
We identified 16 trials involving a total of 616 participants. Eight different types of interventions were studied. Eight trials investigated the effects of electrical brain stimulation (transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES); five trials) or repetitive transcranial magnetic stimulation (rTMS; three trials). Interventions in the remaining studies included exercise programmes (three trials); acupuncture (two trials); self-hypnosis (one trial); transcutaneous electrical nerve stimulation (TENS) (one trial); and a cognitive behavioural programme (one trial). None of the included trials were considered to have low overall risk of bias. Twelve studies had high overall risk of bias, and in four studies risk of bias was unclear. The overall quality of the included studies was weak. Their validity was impaired by methodological weaknesses such as inappropriate choice of control groups. An additional search in November 2014 identified more recent studies that will be included in an update of this review. For tDCS the pooled mean difference between intervention and control groups in pain scores on an 11-point visual analogue scale (VAS) (0-10) was a reduction of -1.90 units (95% confidence interval (CI) -3.48 to -0.33; P value 0.02) in the short term and of -1.87 (95% CI -3.30 to -0.45; P value 0.01) in the mid term. Exercise programmes led to mean reductions in chronic shoulder pain of -1.9 score points for the Short Form (SF)-36 item for pain experience (95% CI -3.4 to -0.4; P value 0.01) and -2.8 pain VAS units (95% CI -3.77 to -1.83; P value < 0.00001); this represented the largest observed treatment effects in the included studies. Trials using rTMS, CES, acupuncture, self-hypnosis, TENS or a cognitive behavioural programme provided no evidence that these interventions reduce chronic pain. Ten trials examined study endpoints other than pain, including anxiety, depression and quality of life, but available data were too scarce for firm conclusions to be drawn. In four trials no side effects were reported with study interventions. Five trials reported transient mild side effects. Overall, a paucity of evidence was found on any serious or long-lasting side effects of the interventions. Evidence is insufficient to suggest that non-pharmacological treatments are effective in reducing chronic pain in people living with SCI. The benefits and harms of commonly used non-pharmacological pain treatments should be investigated in randomised controlled trials with adequate sample size and study methodology. | We searched electronic databases until March 2011 and found 16 randomised controlled trials with a total of 616 participants. We grouped these studies by type of treatment into eight groups: Eight studies were on brain stimulation, of which five used electronic and three magnetic stimulation. Three studies were on exercise programmes, two on acupuncture and one each on self-hypnosis, transcutaneous electrical nerve stimulation (TENS) and a cognitive behavioural programme. The included studies used a range of different methods to measure pain and other outcomes. Comparison groups also varied and included sham interventions, waiting lists and other pain treatments. For any given type of intervention, only a few studies were found, and they included only small numbers of participants. Often the reported detail was insufficient. The overall quality of the studies was low. For instance, several studies used inappropriate comparison groups such as waiting lists. Consequently, the effectiveness of the treatments is uncertain. An additional search in November 2014 identified more recent studies that will be included in an update of this review. For one type of treatment—transcranial direct current stimulation (tDCS)—results from two studies could be combined. The pooled results suggest that tDCS reduced pain in the short term and in the mid term. Also, exercise programmes for chronic shoulder pain provided pain relief. We found no evidence to suggest that repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), acupuncture, self-hypnosis or TENS is better than the respective control interventions for reducing chronic pain. Regarding outcomes other than pain, such as anxiety, depression or quality of life, as well as long-lasting side effects, no overall conclusions were possible, given that data were sparse. The included studies do not permit firm conclusions regarding whether treatments other than medication for chronic SCI pain are effective and safe. Trials with greater numbers of participants and improved study quality are needed to determine the effectiveness and safety of such treatments. |
There are no included studies in this review. The electronic search produced three relevant references, among which we identified two old planned trials that seem never to have started, and one which we excluded a study because it was a report of a case series. This is not an empty review - it is a review full of unanswered questions. Despite growing interest in women’s mental health, the literature in the area of postnatal psychosis is still very limited. It seems that clinicians have no choice but to continue with their current practices guided solely by varied clinical judgement. Women at risk of postnatal psychosis and their relatives are justified to be disappointed in the medical/research fraternity. A post hoc PubMed topic (not methodology-specific) search identified mainly case series. Policy makers have no trial-based evidence upon which to base their guidelines. Certainly, preventive interventions for postnatal psychosis are difficult to justify with confidence without well-designed, well-conducted, and well-reported randomised studies. Available publications suggest that such studies are possible and funders of research may wish to make this work a priority. | This review investigated the best available evidence for interventions aimed at preventing postnatal psychosis. Unfortunately, no studies were found that could be included. Nevertheless, this review raises many unanswered questions and strongly suggests that future research on postnatal psychosis is much needed. Despite a growing interest in women’s mental health, knowledge and research on postnatal psychosis is still very limited. Future well-designed, well-conducted and well-reported studies are necessary to help improve prevention of symptoms and treatment for women with postnatal psychosis. This plain language summary has been written by a consumer Benjamin Gray; Service User and Service User Expert. Rethink Mental Illness. |
Eight trials, which included 1132 participants in total, met the inclusion criteria of this Cochrane review. These trials were at high risk of bias trials. One trial (which included five participants) did not contribute any data to this Cochrane review, and we excluded 13 participants in the remaining trials after randomisation; this left a total of 1114 participants, 510 randomised to non-surgical treatment and 604 to surgical treatment for analysis. The non-surgical treatment was definitive chemoradiotherapy in five trials and definitive radiotherapy in three trials. All participants were suitable for major surgery. Most of the data were from trials that compared chemoradiotherapy with surgery. There was no difference in long-term mortality between chemoradiotherapy and surgery (HR 0.88, 95% CI 0.76 to 1.03; 602 participants; four studies; low quality evidence). The long-term mortality was higher in radiotherapy than surgery (HR 1.39, 95% CI 1.18 to 1.64; 512 participants; three studies; very low quality evidence). There was no difference in long-term recurrence between non-surgical treatment and surgery (HR 0.96, 95% CI 0.80 to 1.16; 349 participants; two studies; low quality evidence). The difference between non-surgical and surgical treatments was imprecise for short-term mortality (RR 0.39, 95% CI 0.11 to 1.35; 689 participants; five studies; very low quality evidence), the proportion of participants with serious adverse in three months (RR 0.61, 95% CI 0.25 to 1.47; 80 participants; one study; very low quality evidence), and proportion of people with local recurrence at maximal follow-up (RR 0.89, 95% CI 0.70 to 1.12; 449 participants; three studies; very low quality evidence). The health-related quality of life was higher in non-surgical treatment between four weeks and three months after treatment (Spitzer Quality of Life Index; MD 0.93, 95% CI 0.24 to 1.62; 165 participants; one study; very low quality evidence). The difference between non-surgical and surgical treatments was imprecise for medium-term health-related quality of life (three months to two years after treatment) (Spitzer Quality of Life Index; MD −0.95, 95% CI −2.10 to 0.20; 62 participants; one study; very low quality of evidence). The proportion of people with dysphagia at the last follow-up visit prior to death was higher with definitive chemoradiotherapy compared to surgical treatment (RR 1.48, 95% CI 1.01 to 2.19; 139 participants; one study; very low quality evidence). Based on low quality evidence, chemoradiotherapy appears to be at least equivalent to surgery in terms of short-term and long-term survival in people with oesophageal cancer (squamous cell carcinoma type) who are fit for surgery and are responsive to induction chemoradiotherapy. However, there is uncertainty in the comparison of definitive chemoradiotherapy versus surgery for oesophageal cancer (adenocarcinoma type) and we cannot rule out significant benefits or harms of definitive chemoradiotherapy versus surgery. Based on very low quality evidence, the proportion of people with dysphagia at the last follow-up visit prior to death was higher with definitive chemoradiotherapy compared to surgery. Based on very low quality evidence, radiotherapy results in less long-term survival than surgery in people with oesophageal cancer who are fit for surgery. However, there is a risk of bias and random errors in these results, although the risk of bias in the studies included in this systematic review is likely to be lower than in non-randomised studies. Further trials at low risk of bias are necessary. Such trials need to compare endoscopic treatment with surgical treatment in early stage oesophageal cancer (carcinoma in situ and Stage Ia), and definitive chemoradiotherapy with surgical treatments in other stages of oesophageal cancer, and should measure and report patient-oriented outcomes. Early identification of responders to chemoradiotherapy and better second-line treatment for non-responders will also increase the need and acceptability of trials that compare definitive chemoradiotherapy with surgery. | Eight studies met the inclusion criteria of this Cochrane review, and seven studies provided information for the review. The non-surgical treatment was chemoradiotherapy only in five studies and radiotherapy only in three studies. We included a total of 1114 participants undergoing non-surgical treatment (510 participants) or surgical treatment (604 participants) in the various analysis in the seven studies that provided information. Methods similar to tossing a coin were used to decide whether a participant received non-surgical treatment or surgical treatment and ensure that the participants in the two groups were similar. Most trials included people who were healthy in aspects other than the condition requiring surgery. The evidence is current up to 4th March 2016. Most information was from trials that compared chemoradiotherapy with surgery. There was no difference in long-term deaths between chemoradiotherapy and surgery in people with oesophageal cancer who are fit for surgery. More people died in radiotherapy than surgery in people with oesophageal cancer who are fit for surgery in the long-term. There was no difference in long-term cancer recurrence between non-surgical treatment and surgery. The difference between non-surgical and surgical treatments were imprecise for short-term deaths, the percentage of participants with serious adverse in three months, and the percentage of participants who had recurrence of cancer in and around the food-pipe. The health-related quality of life (covering aspects such as activity, daily living, health, support of family and friends, and outlook) was higher in non-surgical treatment between four weeks and three months after treatment, although it is unclear what this difference means to the patient. The difference between non-surgical and surgical treatments were imprecise for medium-term health-related quality of life (three months to two years after treatment). Chemoradiotherapy only appears to be at least equivalent to surgery in terms of short-term and long-term survival in people with one type of oesophageal cancer called squamous cell cancer and who are fit for surgery. There is more uncertainty in the comparison of chemoradiotherapy only versus surgery for another type of oesophageal cancer called adenocarcinoma, and we cannot rule out significant benefits or harms of definitive chemoradiotherapy versus surgery in this type of oesophageal cancer. More people had difficulty in swallowing prior to their death after chemoradiotherapy treatment compared to surgical treatment. Radiotherapy only results in less long-term survival than surgery (about 40% increase risk of deaths). Further well-designed studies that measure outcomes that are important for patients are necessary. The quality of evidence was low or very low because the included studies were small and had errors in study design. As a result, there is a lot of uncertainty regarding the results. |
Combining the results of five randomised clinical trials randomising 499 patients with alcoholic hepatitis and/or cirrhosis demonstrated no significant effects of anabolic-androgenic steroids on mortality (relative risk (RR) 1.01, 95% confidence interval (CI) 0.79 to 1.29), liver-related mortality (RR 0.83, 95% CI 0.60 to 1.15), complications of liver disease (RR 1.25, 95% CI 0.74 to 2.10), and liver histology. Anabolic-androgenic steroids did not significantly affect a number of other outcome measures, including sexual function and liver biochemistry. Anabolic-androgenic steroids were not associated with a significantly increased risk of non-serious adverse events (RR 1.14, 95% CI 0.50 to 2.59) or with serious adverse events (RR 4.54, 95% CI 0.57 to 36.30). This systematic review could not demonstrate any significant beneficial effects of anabolic-androgenic steroids on any clinically important outcomes (mortality, liver-related mortality, liver complications, and histology) of patients with alcoholic liver disease. | Several trials have addressed the effects of anabolic-androgenic steroids for alcoholic liver disease. This systematic review could not demonstrate any significant effects of anabolic-androgenic steroids on mortality, liver-related mortality, liver complications, and histology of patients with alcoholic liver disease. Anabolic-androgenic steroid intervention is not associated with a significant increase in non-serious adverse events, but with the seldom occurrence of serious adverse events. Accordingly, there is no evidence supporting the use of anabolic-androgenic steroids for alcoholic liver disease, but further randomised clinical trials may be needed to settle the question. |
Two trials of cytisine (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled risk ratio (RR) of 3.98 (95% confidence interval (CI) 2.01 to 7.87; low-quality evidence). One recent trial comparing cytisine with NRT in 1310 people found a benefit for cytisine at six months (RR 1.43, 95% CI 1.13 to 1.80). One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). This drug is no longer in development. We identified 39 trials that tested varenicline, 27 of which contributed to the primary analysis (varenicline versus placebo). Five of these trials also included a bupropion treatment arm. Eight trials compared varenicline with nicotine replacement therapy (NRT). Nine studies tested variations in varenicline dosage, and 13 tested usage in disease-specific subgroups of patients. The included studies covered 25,290 participants, 11,801 of whom used varenicline. The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.24 (95% CI 2.06 to 2.43; 27 trials, 12,625 people; high-quality evidence). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.08 (95% CI 1.56 to 2.78; 4 trials, 1266 people). The pooled RR for varenicline versus bupropion at six months was 1.39 (95% CI 1.25 to 1.54; 5 trials, 5877 people; high-quality evidence). The RR for varenicline versus NRT for abstinence at 24 weeks was 1.25 (95% CI 1.14 to 1.37; 8 trials, 6264 people; moderate-quality evidence). Four trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The number needed to treat with varenicline for an additional beneficial outcome, based on the weighted mean control rate, is 11 (95% CI 9 to 13). The most commonly reported adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Our analysis of reported serious adverse events occurring during or after active treatment suggests there may be a 25% increase in the chance of SAEs among people using varenicline (RR 1.25; 95% CI 1.04 to 1.49; 29 trials, 15,370 people; high-quality evidence). These events include comorbidities such as infections, cancers and injuries, and most were considered by the trialists to be unrelated to the treatments. There is also evidence of higher losses to follow-up in the control groups compared with the intervention groups, leading to a likely underascertainment of the true rate of SAEs among the controls. Early concerns about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation led to the addition of a boxed warning to the labelling in 2008. However, subsequent observational cohort studies and meta-analyses have not confirmed these fears, and the findings of the EAGLES trial do not support a causal link between varenicline and neuropsychiatric disorders, including suicidal ideation and suicidal behaviour. The evidence is not conclusive, however, in people with past or current psychiatric disorders. Concerns have also been raised that varenicline may slightly increase cardiovascular events in people already at increased risk of those illnesses. Current evidence neither supports nor refutes such an association, but we await the findings of the CATS trial, which should establish whether or not this is a valid concern. Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and three-fold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion or with NRT. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The most frequently recorded adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research. Future trials of cytisine may test extended regimens and more intensive behavioural support. | We searched for randomised controlled trials testing varenicline, cytisine or dianicline. We found 39 studies of varenicline compared to placebo, bupropion or nicotine patches. We also found four trials of cytisine, one of which compared it to nicotine replacement therapy. We include one trial of dianicline, which is no longer in development, and so not available to use as a quitting aid. To be included, trials had to report quit rates at least six months from the start of treatment. We preferred the strictest available definition of quitting, and results which had been biochemically confirmed by testing blood or bodily fluids.We conducted full searches up to May 2015, although we have also included several key trials published after that date. From the information we found (27 trials, 12,625 people), varenicline at standard dose more than doubled the chances of quitting compared with placebo. Low-dose varenicline (four trials, 1266 people) roughly doubled the chances of quitting, and reduced the number and severity of side effects. The number of people stopping smoking with varenicline was higher than with bupropion (five trials, 5877 people) or with NRT (eight trials, 6264 people). Based on the evidence so far, we can calculate that varenicline delivers one extra successful quitter for every 11 people treated, compared with smokers trying to quit without varenicline. The most common side effect of varenicline is nausea, but this is mostly at mild or moderate levels and usually clears over time. People taking varenicline appear to have about a 25% increased chance of a serious adverse event, although these include many which are unrelated to the treatment. We also note that more people were lost from the control groups than from the varenicline groups by the end of the trials, which may mean that the count of events in the control groups is lower than it should be. After varenicline became available to use, there were concerns that it could be linked with an increase in depressed mood, agitation, or suicidal thinking and behaviour in some smokers. However, the latest evidence does not support a link between varenicline and these disorders, although people with past or current psychiatric illness may be at slightly higher risk. There have also been concerns that varenicline may slightly increase heart and circulatory problems in people already at increased risk of these illnesses. The evidence is currently unclear whether or not they are caused or made worse by varenicline, but we should have clearer answers to these questions when a further study is published later this year. The varenicline studies were generally of high quality, providing evidence that we consider to be reliable and robust. We rate the quality of the evidence comparing varenicline with NRT as moderate quality (we are reasonably confident of the stability of the evidence), since in some of them the participants knew which treatment they were receiving (i.e. non-blinded open-label trials). We judge the evidence from the cytsine trials to be of low quality (we have limited confidence in the evidence), as there are only two trials, with relatively low numbers included. |
We identified 16 qualifying randomised controlled trials (RCTs) (7 statin, 9 fibrate). Thirteen of these trials (involving 62,197 participants) provided data on incident melanomas (6 statin, 7 fibrate). A total of 66 melanomas were reported in groups receiving the experimental drug and 86 in groups receiving placebo or other control therapies. For statin trials this translated to an odds ratio of 0.90 (95% confidence interval 0.56 to 1.44) and for fibrate trials an odds ratio of 0.58 (95% confidence interval 0.19 to 1.82). Subgroup analyses failed to show statistically significant differences in melanoma outcomes by gender, melanoma occurrence after two years of participation in trial, stage or histology, or trial funding. Subgroup analysis by type of fibrate or statin also failed to show statistically significant differences, except for the statin subgroup analysis which showed reduced melanoma incidence for lovastatin, based on one trial only (odds ratio 0.52, 95% confidence interval 0.27 to 0.99). The melanoma outcomes data collected in this review of RCTs of statins and fibrates does not exclude the possibility that these drugs prevent melanoma. There was a 10% and 42% reduction for participants on statins and fibrates, respectively, however these results were not statistically significant. Until further evidence is established, limiting exposure to ultraviolet radiation remains the most effective way to reduce the risk of melanoma. | Some studies have suggested that medicines (such as statins and fibrates) taken to lower blood cholesterol may reduce the risk of melanoma skin cancer. Our review of 16 studies did not find any clear evidence to support such a suggestion, but we cannot exclude a useful effect of such drugs until more studies become available. |
In updating the review, 49 new studies were identified for inclusion. A total of 81 trials involving more than 11,000 health professionals are now included in the review. Based on 30 trials (36 comparisons), the median adjusted RD in compliance with desired practice was 6% (interquartile range 1.8 to 15.9) when any intervention in which educational meetings were a component was compared to no intervention. Educational meetings alone had similar effects (median adjusted RD 6%, interquartile range 2.9 to 15.3; based on 21 comparisons in 19 trials). For continuous outcomes the median adjusted percentage change relative to control was 10% (interquartile range 8 to 32%; 5 trials). For patient outcomes the median adjusted RD in achievement of treatment goals was 3.0 (interquartile range 0.1 to 4.0; 5 trials). Based on univariate meta-regression analyses of the 36 comparisons with dichotomous outcomes for professional practice, higher attendance at the educational meetings was associated with larger adjusted RDs (P < 0.01); mixed interactive and didactic education meetings (median adjusted RD 13.6) were more effective than either didactic meetings (RD 6.9) or interactive meetings (RD 3.0). Educational meetings did not appear to be effective for complex behaviours (adjusted RD -0.3) compared to less complex behaviours; they appeared to be less effective for less serious outcomes (RD 2.9) than for more serious outcomes. Educational meetings alone or combined with other interventions, can improve professional practice and healthcare outcomes for the patients. The effect is most likely to be small and similar to other types of continuing medical education, such as audit and feedback, and educational outreach visits. Strategies to increase attendance at educational meetings, using mixed interactive and didactic formats, and focusing on outcomes that are likely to be perceived as serious may increase the effectiveness of educational meetings. Educational meetings alone are not likely to be effective for changing complex behaviours. | Eighty-one trials that evaluated the effects of educational meetings were included in this review. Based on these studies, we concluded that educational meetings alone or combined with other interventions can improve professional practice and the achievement of treatment goals by patients. The effect on professional practice tended to be small but varied between studies, and the effect on patient outcomes was generally less. It is not possible to explain the observed differences in effect with confidence but it appeared that higher attendance at the meetings was associated with greater effects, that mixed interactive and didactic education was more effective than either alone, and that the effects were less for more complex behaviours and less serious outcomes. |
Fifteen studies (1644 elderly women) were included. Three studies compared single dose with short-course treatment (3 to 6 days), six compared single dose with long-course treatment (7 to 14 days) and six compared short- with long-course treatment. Methodological quality of all studies was low except for a more recent geriatric study. There was a significant difference for persistent UTI between single dose and short-course treatment (RR 2.01, 95% CI 1.05 to 3.84) and single versus long-course treatment (RR 1.93, 1.01 to 3.70 95% CI), in the short-term (< 2 weeks post-treatment) but not at long-term follow-up or on clinical outcomes. Patients preferred single dose treatment (RR 0.73, 95% CI 0.60 to 0.88) to long-course treatments, but this was based on one study comparing different antibiotics. Short versus longer treatments showed no significant difference in efficacy. Rate of adverse drug reactions increased significantly with longer treatment durations in only one study. Short-course treatment (3 to 6 days) could be sufficient for treating uncomplicated UTIs in elderly women, although more studies on specific commonly prescribed antibiotics are needed. | We identified 15 studies (1644 elderly women) comparing single dose, short-course (3 to 6 days) and long course (7 to 14 days) antibiotic treatment for uncomplicated symptomatic UTI in elderly women. Our review suggests that single dose treatments are less effective than short or long courses, but better accepted by the patients. On the other hand longer courses may have more side effects. On the basis of the evidence available at present, an antibiotic treatment of 3 to 6 days could be sufficient for treating uncomplicated UTIs in elderly women, although more studies on specific, commonly prescribed antibiotics are needed. |
Nineteen studies (11 prevention, 8 treatment; 1,861 participants) were included. There was no difference in mortality between ANP and control in either the low or high dose prevention studies. Low (but not high) dose ANP was associated with a reduced need for RRT in the prevention studies (RR 0.32, 95% CI 0.14 to 0.71). Length of hospital and ICU stay were significantly shorter in the low dose ANP group. For established AKI, there was no difference in mortality with either low or high dose ANP. Low (but not high) dose ANP was associated with a reduction in the need for RRT (RR 0.54, 95% CI 0.30 to 0.98). High dose ANP was associated with more adverse events (hypotension, arrhythmias). After major surgery there was a significant reduction in RRT requirement with ANP in the prevention studies (RR 0.56, 95% CI 0.32 to 0.99), but not in the treatment studies. There was no difference in mortality between ANP and control in either the prevention or treatment studies. There was a reduced need for RRT with low dose ANP in patients undergoing cardiovascular surgery (RR 0.35, 95% CI 0.18 to 0.70). ANP was not associated with outcome improvement in either radiocontrast nephropathy or oliguric AKI. ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI and should be further explored in these two settings. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases hypotension and arrhythmias. | Atrial natriuretic peptide (ANP) has been shown to increase urine production and to reduce kidney inflammation. The aim of this review was to investigate the use of ANP in preventing AKI and treating established AKI. We identified 19 studies (11 prevention and 8 treatment) using low or high dose ANP, enrolling 1,861 patients. There was no difference in the number of deaths between ANP and control for studies preventing or treating AKI. The need for dialysis was significantly lower in both the low dose ANP treatment and prevention studies as well as for patients undergoing major surgery. The length of time spend in hospital and ICU was shorter for patients receiving low dose ANP. High dose ANP was associated with more hypotension and cardiac arrhythmias in patients with established AKI. ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases in hypotension and arrhythmias. |
We found no randomised trials for inclusion in this review. One study is ongoing. As we did not identify any randomised trials for inclusion in this review, we are unable to comment on implications for practice at this stage. Although evidence from animals studies has supported a fetal neuroprotective role for melatonin when administered to the mother during pregnancy, no trials assessing melatonin for fetal neuroprotection in pregnant women have been completed to date. However, there is currently one ongoing randomised controlled trial (with an estimated enrolment target of 60 pregnant women) which examines the dose of melatonin, administered to women at risk of imminent very preterm birth (less than 28 weeks' gestation) required to reduce brain damage in the white matter of the babies that were born very preterm. Further high-quality research is needed and research efforts should directed towards trials comparing melatonin with either no intervention (no treatment or placebo), or with alternative agents aimed at providing fetal neuroprotection (such as magnesium sulphate for the very preterm infant). Such trials should evaluate maternal and infant short- and longer-term outcomes (including neurosensory disabilities such as cerebral palsy), and consider the costs of care. | We did not find any completed randomised controlled trials that assessed melatonin given to the mother during pregnancy to help protect the baby's brain. One ongoing trial (planning to include 60 women) was identified. This trial is designed to determine what dose of melatonin can reduce brain injury for babies when given to their mothers before very preterm birth (before 28 weeks of pregnancy). Further studies are needed to establish whether melatonin given to the mother in pregnancy can protect the baby's brain against brain injury. The babies in these trials need to be followed up over a long period so that we can monitor the effects of melatonin on childhood development, including impairments or disabilities such as cerebral palsy. |
Ten studies enrolling 630 participants were included. Overall, the quality of evidence was suboptimal due to the small number of included studies enrolling small numbers of participants; short follow-up in each study; only a few studies in each comparison category; and major concerns with methodological bias. Four studies (293 participants) contributed to the comparison of TwHF versus non-TwHF. TwHF significantly increased complete remission (RR 1.46, 95% CI 1.18 to 1.80) and complete or partial remission (RR 1.26, 95% CI 1.10 to 1.44) without escalating the adverse events profile at the last follow-up (12 to 16 months). Four studies (223 participants) compared TwHF with prednisone. There were no statistically significant differences between complete remission, partial remission, and complete or partial remission. Two studies (114 participants) contributed to the comparison of TwHF versus cyclophosphamide (CPA) at the last follow-up (3 to 12 months). There were no statistically significant differences between complete, partial, or complete or partial remission. One study (46 participants) reported TwHF was associated with a significantly lower serum creatinine compared with CPA (MD -14.00 μmol/L, 95% CI -26.43 to -1.57). No serious adverse events of TwHF were observed. One study (37 participants) reported TwHF was associated with a significantly lower risk of psychosis when compared to prednisone (RR 0.11, 95% CI 0.01 to 0.75), and two studies showed a significantly lower risk of hair loss with TwHF when compared to CPA ((2 studies, 114 participants): RR 0.11, 95% CI 0.02 to 0.59). TwHF may have an add-on effect on remission in patients with primary NS. There was insufficient evidence to assess if TwHF was as effective as prednisone or CPA. More methodologically sound and sufficiently powered studies, with adequate follow-up would help to better inform management options for the use of TwHF for primary NS. TwHF should be further directly compared with other widely used immunosuppressive agents after the superiority over placebo or no treatment has been clearly established. | In this review we investigated the use of TwHF as an immunosuppressive therapy for patients with primary NS. We only considered two standardised TwHF extracts which have lower toxicity profiles and fewer adverse effects than other non-standardised preparations. We reviewed the evidence from 10 randomised studies enrolling 630 Chinese patients with primary NS. Of these, four studies (293 patients) reported that when TwHF was used there was a significantly increased number of patients achieving complete, and complete or partial remission without increasing adverse events. There were no significant differences in complete, partial, or complete or partial remission when TwHF was compared with prednisone in four studies (223 patients). There were also no significant differences in complete, partial, or complete or partial remission when TwHF was compared with CPA in two studies (114 patients). One study reported TwHF significantly improved kidney function (decreased serum creatinine) when compared with CPA. TwHF was associated with a lower risk of psychosis than prednisone; and there was less likelihood of hair loss when compared to CPA. The quality of evidence was poor; there were only 10 studies, enrolling a total of 630 patients; follow-up was short; the maximum number of studies included in a comparison was four; and we had major concerns over the quality of the included studies. TwHF may have an add-on effect on remission in patients with primary NS; however there is insufficient evidence to assess if TwHF is as effective as prednisone or CPA. |
Our searches returned 546 trials, of which five met our inclusion criteria. These studies randomised 14,252 children to receive either an intervention or usual care. All studies were conducted in the Northern Hemisphere. Three interventions used a leukotriene receptor antagonist, one used omalizumab or a boost of inhaled corticosteroids, and the largest study, (12,179 children), used a medication reminder letter. Whilst the risk of bias within individual studies was generally low, we downgraded the evidence quality due to imprecision associated with low participant numbers, poor consistency between studies, and indirect outcome ascertainment. A US study of 513 children with mild/severe asthma and allergic sensitisation was the only study to provide data for our primary outcome. In this study, the proportion of participants experiencing an exacerbation requiring oral corticosteroids or hospital admission in the 90 days after school return was significantly reduced to 11.3% in those receiving omalizumab compared to 21.0% in those receiving placebo (odds ratio 0.48, 95% confidence interval 0.25 to 0.92, moderate-quality evidence). The remaining studies used alternative exacerbation definitions. When data from two leukotriene receptor antagonist studies with comparable outcomes were combined in a random-effects model, there was no evidence of an effect upon exacerbations. There was no evidence that a seasonal medication reminder letter decreased unscheduled contacts for a respiratory diagnosis between September and December. Four studies recorded adverse events. There was no evidence that the proportion of participants experiencing at least one adverse event differed between intervention and usual care groups. Lack of data prevented planned subgroup and sensitivity analyses. Seasonal omalizumab treatment from four to six weeks before school return might reduce autumn asthma exacerbations. We found no evidence that this strategy is associated with increased adverse effects other than injection site pain, but it is costly. There were no data upon which to judge the effect of this or other seasonal interventions on asthma control, quality of life, or asthma-related death. In future studies definitions of exacerbations should be provided, and standardised where possible. To investigate possible differential effects according to subgroup, participants in future trials should be well characterised with respect to baseline asthma severity and exacerbation history in addition to age and gender. | Our searches found 546 trials, of which five were relevant. In total, 14,252 children were randomly assigned to receive either an intervention targeting autumn asthma attacks or usual care. Four small studies (approximately 200 to 1200 children in each) gave children extra asthma medication; these additional medications were omalizumab, leukotriene receptor antagonist tablets, or increased doses of inhaled steroids. One study sent a medication reminder letter over the summer holidays to parents of children with asthma. One trial gave children either omalizumab or placebo. Omalizumab is an antibody designed to alter the immune response. It was given by injection regularly over four to six weeks before school return (i.e. over the bulk of the summer holidays). The children in this study had known allergic asthma. The study showed that omalizumab might reduce autumn attacks. Eleven per cent of those receiving omalizumab had an asthma attack during the first 90 days compared to 21% of those receiving placebo. Three studies used leukotriene receptor antagonist tablets, either montelukast or pranlukast. Although the results of one study suggested that seasonal montelukast might reduce autumn attacks, there was no evidence of reduced attacks in the other two later trials, including a second larger trial of montelukast. There was no evidence that sending a reminder letter reduces the number of children requiring an unplanned healthcare contact. No study provided evidence that the total number of children experiencing adverse events was greater in the intervention than in the usual care group. Our findings were limited by the small numbers of studies identified and because these studies used different interventions and definitions of asthma exacerbations. Further research is needed to better understand how to prevent seasonal attacks, including interventions suitable for children with mild asthma, where expensive and painful treatments are not justified. |
We included six published RCTs, conducted in the USA (5 RCTs) and Israel (1 RCT), with 1097 children and adolescents (11 to 18 years old), in the review. We are very uncertain about the effect of client feedback on improvement of symptoms, as reported by youth in the short term because we considered evidence to be of very low-certainty due to high risk of bias and very serious inconsistency in the effect estimates from the different studies. Similarly, we are very uncertain about the effect of client feedback on treatment acceptability, due to high risk of bias, imprecision in the results, and indirectness of measuring the outcome (RR 1.08, 95% CI 0.73 to 1.61; 2 studies, 237 participants; very low-certainty). Overall, most studies reported and carried out randomisation and allocation concealment adequately. None of the studies were blinded or attempted to blind participants and personnel and were at high risk of performance bias, and only one study had blind outcome assessors. All of the studies were at high or unclear risk of attrition bias mainly due to poor, non-transparent reporting of participants' flow through the studies. Due to the paucity of high-quality data and considerable inconsistency in results from different studies, there is currently insufficient evidence to reach any firm conclusions regarding the role of client feedback in psychological therapies for children and adolescents with mental health problems, and further research on this important topic is needed. Future studies should avoid risks of performance, detection and attrition biases, as seen in the studies included in this review. Studies from countries other than the USA are needed, as well as studies including children younger than 10 years. | There have been few investigations of client feedback in psychological therapies for children and adolescents with mental health problems. Most of them were carried out in the USA with older children and adolescents (11 to 18 years old). There was no clear evidence supporting the effectiveness of client feedback in psychological therapy for children and adolescents. It cannot be ruled out that client feedback has positive effects on psychotherapy outcomes in children and adolescents. High-quality studies are needed to provide sufficient evidence. Future studies should also include younger children, and should take place in countries other than the USA. |
We identified 56 eligible studies involving 15,596 adults with CKD. Risks of bias in the included studies was generally high or unclear for more than half of studies in all of the risk of bias domains we assessed; no study was low risk for allocation concealment, blinding of outcome assessment and attrition from follow-up. In network analyses, there was moderate to low confidence that epoetin alfa (OR 0.18, 95% CI 0.05 to 0.59), epoetin beta (OR 0.09, 95% CI 0.02 to 0.38), darbepoetin alfa (OR 0.17, 95% CI 0.05 to 0.57), and methoxy polyethylene glycol-epoetin beta (OR 0.15, 95% CI 0.03 to 0.70) prevented blood transfusions compared to placebo. In very low quality evidence, biosimilar ESA therapy was possibly no better than placebo for preventing blood transfusions (OR 0.27, 95% CI 0.05 to 1.47) with considerable imprecision in estimated effects. We could not discern whether all ESAs were similar or different in their effects on preventing blood transfusions and our confidence in the comparative effectiveness of different ESAs was generally very low. Similarly, the comparative effects of ESAs compared with another ESA, placebo or no treatment on all-cause mortality were imprecise. All proprietary ESAs increased the odds of hypertension compared to placebo (epoetin alfa OR 2.31, 95% CI 1.27 to 4.23; epoetin beta OR 2.57, 95% CI 1.23 to 5.39; darbepoetin alfa OR 1.83, 95% CI 1.05 to 3.21; methoxy polyethylene glycol-epoetin beta OR 1.96, 95% CI 0.98 to 3.92), while the effect of biosimilar ESAs on developing hypertension was less certain (OR 1.18, 95% CI 0.47 to 2.99). Our confidence in the comparative effects of ESAs on hypertension was low due to considerable imprecision in treatment estimates. The comparative effects of all ESAs on cardiovascular mortality, myocardial infarction (MI), stroke, and vascular access thrombosis were uncertain and network analyses for major cardiovascular events, end-stage kidney disease (ESKD), fatigue and breathlessness were not possible. Effects of ESAs on fatigue were described heterogeneously in the available studies in ways that were not useable for analyses. In the CKD setting, there is currently insufficient evidence to suggest the superiority of any ESA formulation based on available safety and efficacy data. Directly comparative data for the effectiveness of different ESA formulations based on patient-centred outcomes (such as quality of life, fatigue, and functional status) are sparse and poorly reported and current research studies are unable to inform care. All proprietary ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, and methoxy polyethylene glycol-epoetin beta) prevent blood transfusions but information for biosimilar ESAs is less conclusive. Comparative treatment effects of different ESA formulations on other patient-important outcomes such as survival, MI, stroke, breathlessness and fatigue are very uncertain. For consumers, clinicians and funders, considerations such as drug cost and availability and preferences for dosing frequency might be considered as the basis for individualising anaemia care due to lack of data for comparative differences in clinical benefits and harms. | Several drugs are available to treat anaemia for people who have kidney disease but whether these drugs are similar or different in their ability to improve symptoms of anaemia, such as tiredness and breathlessness, and whether they are equally safe based on their risks of causing a stroke or a heart attack, is not clear. This is because research studies that compare the effects of one drug directly with another are not common. We have found 56 studies that measure the safety and how these drugs help to improve how patients who have kidney disease feel, function and survive that have involved 15,596 people. Our last search of the literature was in February 2014. We are somewhat confident that four of the drugs (epoetin alfa, epoetin beta, darbepoetin beta and methoxy polyethylene glycol-epoetin beta) are better than a placebo injection to prevent patients needing to have a blood transfusion. We are less certain that biosimilar drugs are better than placebo to help patients avoid a blood transfusion. All erythropoiesis-stimulating agents cause high blood pressure, but we cannot be very sure if biosimilar products have effects on blood pressure. We cannot be confident in the other important effects of these drugs - we are not sure whether the drugs are similar or different in their effects on the chances of death, a heart attack or stroke; the risk of having a clot in a fistula or vascular catheter needed for dialysis; or the chances of needing dialysis for people who have milder kidney disease. We are unsure whether the different drugs are better at improving symptoms such as tiredness or breathlessness than others as the available research studies generally do not measure these aspects of treatment very well. Overall, whether different drugs are safer or better at treating symptoms of anaemia for people with kidney disease is poorly known. It is likely that most if not all the drugs prevent the need for a patient to require a blood transfusion. The choice of which drug to use to treat anaemia when a patient has kidney disease can be decided between patients and health professionals based on shared preferences for how frequently the drug is given and considering drug costs and availability. |
Primary outcome Mean improvement in the maintenance of wakefulness test was available for two of the five identified trials accounting for 48 participants. The mean difference +2.52(95% confidence interval (CI) -2.32 to +7.37), was not significant and there was marked heterogeneity across these studies (I2= 50%). Secondary outcomes Mean improvement in the Epworth Sleepiness Scale was available in four trials accounting for 101 participants. The mean difference was -2.26 (95% CI -3.78to -0.73), significantly in favor of modafinil with marked heterogeneity across the studies (I2= 84%). There was no evidence for any treatment benefit on the multiple sleep latency test or quality of life. There is low quality evidence from two small trials that psychostimulants do not significantly improve the maintenance of wakefulness test in myotonic dystrophy. There is low quality evidence from four studies that modafinil significantly improves the Epworth Sleepiness Scale. More randomized trials are needed to evaluate the efficacy and safety of psychostimulants. | In this updated review there were few randomized controlled trials which evaluated the efficacy and safety of psychostimulants in myotonic dystrophy. One randomized controlled trial of selegiline involving 11 participants did not demonstrate any benefit. Four studies of another drug modafinil suggested inconsistent and slight benefits. Only two of these studies used the gold standard test, a sleepiness scale, to evaluate hypersomnia and found non significant improvement. In these four studies modafinil seemed well tolerated. Further randomized trials are needed to determine the utility of psychostimulants for myotonic dystrophy. |
We identified 41 randomised controlled trials (RCTs) involving 194,035 participants from 6422 reports. We assessed studies as having high or unclear risk of bias across multiple domains. Low-quality evidence evidence suggests that providing CVD risk scores may have little or no effect on CVD events compared with usual care (5.4% versus 5.3%; RR 1.01, 95% confidence interval (CI) 0.95 to 1.08; I² = 25%; 3 trials, N = 99,070). Providing CVD risk scores may reduce CVD risk factor levels by a small amount compared with usual care. Providing CVD risk scores reduced total cholesterol (MD −0.10 mmol/L, 95% CI −0.20 to 0.00; I² = 94%; 12 trials, N = 20,437, low-quality evidence), systolic blood pressure (MD −2.77 mmHg, 95% CI −4.16 to −1.38; I² = 93%; 16 trials, N = 32,954, low-quality evidence), and multivariable CVD risk (SMD −0.21, 95% CI −0.39 to −0.02; I² = 94%; 9 trials, N = 9549, low-quality evidence). Providing CVD risk scores may reduce adverse events compared with usual care, but results were imprecise (1.9% versus 2.7%; RR 0.72, 95% CI 0.49 to 1.04; I² = 0%; 4 trials, N = 4630, low-quality evidence). Compared with usual care, providing CVD risk scores may increase new or intensified lipid-lowering medications (15.7% versus 10.7%; RR 1.47, 95% CI 1.15 to 1.87; I² = 40%; 11 trials, N = 14,175, low-quality evidence) and increase new or increased antihypertensive medications (17.2% versus 11.4%; RR 1.51, 95% CI 1.08 to 2.11; I² = 53%; 8 trials, N = 13,255, low-quality evidence). There is uncertainty whether current strategies for providing CVD risk scores affect CVD events. Providing CVD risk scores may slightly reduce CVD risk factor levels and may increase preventive medication prescribing in higher-risk people without evidence of harm. There were multiple study limitations in the identified studies and substantial heterogeneity in the interventions, outcomes, and analyses, so readers should interpret results with caution. New models for implementing and evaluating CVD risk scores in adequately powered studies are needed to define the role of applying CVD risk scores in primary CVD prevention. | We searched scientific databases for randomised trials (clinical studies that randomly put people into different treatment groups) that systematically provided CVD risk scores or usual care to adults without a history of heart disease or stroke. The evidence is current to March 2016. Funding for the majority of trials came from government sources or pharmaceutical companies. We identified 41 trials that included 194,035 participants. Many of the studies had limitations. Low-quality evidence suggests that providing CVD risk scores had little or no effect on the number of people who develop heart disease or stroke. Providing CVD risk scores may reduce CVD risk factor levels (like cholesterol, blood pressure, and multivariable CVD risk) by a small amount and may increase cholesterol-lowering and blood pressure-lowering medication prescribing in higher risk people. Providing CVD risk scores may reduce harms, but the results were imprecise. There is low-quality evidence to guide the use of CVD risk scores in clinical practice. Studies had multiple limitations and used different methods to provide CVD risk scores. It is likely that further research will influence these results. |
We included 38 studies involving 9445 participants. Among studies that measured diet adherence outcomes between an intervention group and a control/usual care group, 32 out of 123 diet adherence outcomes favoured the intervention group, 4 favoured the control group whereas 62 had no significant difference between groups (assessment was impossible for 25 diet adherence outcomes since data and/or statistical analyses needed for comparison between groups were not provided). Interventions shown to improve at least one diet adherence outcome are: telephone follow-up, video, contract, feedback, nutritional tools and more complex interventions including multiple interventions. However, these interventions also shown no difference in some diet adherence outcomes compared to a control/usual care group making inconclusive results about the most effective intervention to enhance dietary advice. The majority of studies reporting a diet adherence outcome favouring the intervention group compared to the control/usual care group in the short-term also reported no significant effect at later time points. Studies investigating interventions such as a group session, individual session, reminders, restriction and behaviour change techniques reported no diet adherence outcome showing a statistically significant difference favouring the intervention group. Finally, studies were generally of short duration and low quality, and adherence measures varied widely. There is a need for further, long-term, good-quality studies using more standardized and validated measures of adherence to identify the interventions that should be used in practice to enhance adherence to dietary advice in the context of a variety of chronic diseases. | We identified 38 studies involving 9445 participants examining several types of interventions for enhancing adherence to dietary advice for preventing and managing many chronic diseases. The main chronic diseases involved were cardiovascular diseases, diabetes, hypertension, and renal diseases. Interventions shown to improve at least one diet adherence outcome are: telephone follow-up, video, contract, feedback, nutritional tools and more complex interventions including multiple interventions. However, these interventions also showed no difference in some diet adherence outcomes compared to a control/usual care group making the results inconclusive about the most effective intervention to enhance dietary advice. Interestingly, all studies including clients with renal diseases reported at least one diet adherence outcome showing a statistically significant difference favouring the intervention group, no matter which intervention was provided. The majority of studies reporting a diet adherence outcome favouring the intervention group compared to the control/usual care group in the short-term also reported no significant effect at later time points. Studies investigating interventions such as a group session, individual session, reminders, restriction and behaviour change techniques reported no diet adherence outcome showing a statistically significant difference favouring the intervention group. Finally, interventions were generally of short duration, studies used different methods for measuring adherence and the quality of the studies was generally low. |
Twelve studies were identified in the searches and seven of these were eligible for inclusion in the review. Five studies, involving 260 participants, provided data for analysis. One study showed that cognitive behaviour therapy significantly reduced the affective component of pain (feelings about pain), mean difference -0.99 (95% confidence interval -1.62 to -0.36), but not the sensory component (pain intensity), mean difference 0.00 (95% confidence interval -9.39 to 9.39). One study of family psycho-education was not associated with a reduction in depression. Another study evaluating cognitive behavioural therapy had inconclusive results for the assessment of coping strategies, and showed no difference between groups assessed on health service utilisation. In addition, family home-based cognitive behavioural therapy did not show any difference compared to disease education. One study of patient education on health beliefs showed a significant improvement in attitudes towards health workers, mean difference -4.39 (95% CI -6.45 to -2.33) and medication, mean difference -1.74 (95% CI -2.98 to -0.50). Nonetheless, these results may not apply across all ages, severity of sickle cell disease, types of pain (acute or chronic), or setting. Evidence for the efficacy of psychological therapies in sickle cell disease is currently limited. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions in sickle cell disease. | We searched for randomised or quasi-randomised controlled trials which compared psychological treatments to each other or to no treatment in sickle cell disease. We included seven studies in the review, of which five, with 260 people, had data we could enter into the review. One study showed that cognitive behaviour therapy reduced the affective part of pain (feelings about pain), but not the sensory part (pain intensity). Another study of this therapy had inconclusive results for coping strategies and showed no difference on how different groups used the health service. A study using cognitive behavioural therapy with teenagers and their families at home did not show any difference when compared with education about sickle cell disease. One education study did not show a reduction in depression. Furthermore, one study in patient education helped improve attitudes to healthcare workers and medication use in adolescents and young adults. The authors believe that some patient education seems relevant for children, adolescents and young adults, while methods to improve the ability to cope in both children and adults are important. Nonetheless, these results may not apply to across all ages, clinical severity, types of pain (acute or chronic) that people with sickle cell disease have, or which country they live in. More research needs to be done in this area. |
Eighteen RCTs were included in the review, of which 14 were included in the meta-analyses (in total 2279 couples). The evidence was current to October 2013. The quality of the evidence was low or very low for most comparisons . The main limitations in the evidence were failure to describe study methods, serious imprecision and attrition bias. Ten RCTs compared different methods of timing for IUI. We found no evidence of a difference in live birth rates between hCG injection versus LH surge (odds ratio (OR) 1.0, 95% confidence interval (CI) 0.06 to 18, 1 RCT, 24 women, very low quality evidence), urinary hCG versus recombinant hCG (OR 1.17, 95% CI 0.68 to 2.03, 1 RCT, 284 women, low quality evidence) or hCG versus GnRH agonist (OR 1.04, 95% CI 0.42 to 2.6, 3 RCTS, 104 women, I2 = 0%, low quality evidence). Two RCTs compared the optimum time interval from hCG injection to IUI, comparing different time frames that ranged from 24 hours to 48 hours. Only one of these studies reported live birth rates, and found no difference between the groups (OR 0.52, 95% CI 0.27 to 1.00, 1 RCT, 204 couples). One study compared early versus late hCG administration and one study compared different dosages of hCG, but neither reported the primary outcome of live birth. We found no evidence of a difference between any of the groups in rates of pregnancy or adverse events (multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS)). However, most of these data were very low quality. There is insufficient evidence to determine whether there is any difference in safety and effectiveness between different methods of synchronization of ovulation and insemination. More research is needed. | We found 18 randomised controlled trials, all comparing different timing methods in one treatment cycle for IUI, with a total of 2279 couples. The evidence was current to October 2013. We found no evidence of a difference in live birth rates between timing methods. We also found no evidence of a difference between any of the groups in rates of pregnancy or adverse events (multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS)). Most of the evidence was of low or very low quality. The main limitations were poor reporting of study methods, imprecision and losses to follow up. More research is needed. |
In the original version of the review we identified two RCTs; in this update we identified no additional studies. One trial (135 participants) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline-induced cardiac dysfunction. The other trial (68 participants) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, adenosine triphosphate, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations. The RCT on enalapril showed no statistically significant differences in overall survival, mortality due to heart failure, development of clinical heart failure, and quality of life between treatment and control groups. A post-hoc analysis showed a decrease (that is improvement) in one measure of cardiac function (left ventricular end-systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Participants treated with enalapril had a higher risk of dizziness or hypotension (risk ratio 7.17, 95% confidence interval 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013). The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function, and adverse events between treatment and control groups. Only one trial evaluated the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity. Only one trial evaluated the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatments on echocardiographic function and clinical outcomes. We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors. High-quality studies should be performed. | We identified two randomised studies evaluating two different drugs in two different types of patients. One of these drugs, an angiotensin-converting enzyme (ACE) inhibitor (enalapril), had a short-term beneficial effect on heart function in survivors of childhood cancer with asymptomatic cardiac problems caused by anthracyclines compared with placebo. However, the drug had no significant beneficial effect on other important outcomes and was associated with side effects such as dizziness and fatigue. This study was of reasonable/good quality. The other study was of low quality and found no effect of a short treatment with phosphocreatine in childhood leukaemia patients with symptomatic or asymptomatic cardiac problems compared with a control treatment with vitamin C, adenosine triphosphate, vitamin E, and oral coenzyme Q10. We could make no definitive conclusions about treatment options for anthracycline-induced cardiac problems in childhood cancer patients and survivors. High-quality studies are needed to determine if there are drugs that improve heart function in these patients. |
Seventeen studies (14 ITS and 3 CBA studies) met the inclusion criteria in this updated version of the review. The ITS studies evaluated the effects of: introducing or changing regulations that laid down safety and health requirements for the construction sites (nine studies), a safety campaign (two studies), a drug-free workplace programme (one study), a training programme (one study), and safety inspections (one study) on fatal and non-fatal occupational injuries. One CBA study evaluated the introduction of occupational health services such as risk assessment and health surveillance, one evaluated a training programme and one evaluated the effect of a subsidy for upgrading to safer scaffoldings. The overall risk of bias of most of the included studies was high, as it was uncertain for the ITS studies whether the intervention was independent from other changes and thus could be regarded as the main reason of change in the outcome. Therefore, we rated the quality of the evidence as very low for all comparisons. Compulsory interventions Regulatory interventions at national or branch level may or may not have an initial effect (effect size (ES) of −0.33; 95% confidence interval (CI) −2.08 to 1.41) and may or may not have a sustained effect (ES −0.03; 95% CI −0.30 to 0.24) on fatal and non-fatal injuries (9 ITS studies) due to highly inconsistent results (I² = 98%). Inspections may or may not have an effect on non-fatal injuries (ES 0.07; 95% CI −2.83 to 2.97; 1 ITS study). Educational interventions Safety training interventions may result in no significant reduction of non-fatal injuries (1 ITS study and 1 CBA study). Informational interventions We found no studies that had evaluated informational interventions alone such as campaigns for risk communication. Persuasive interventions We found no studies that had evaluated persuasive interventions alone such as peer feedback on workplace actions to increase acceptance of safe working methods. Facilitative interventions Monetary subsidies to companies may lead to a greater decrease in non-fatal injuries from falls to a lower level than no subsidies (risk ratio (RR) at follow-up: 0.93; 95% CI 0.30 to 2.91 from RR 3.89 at baseline; 1 CBA study). Multifaceted interventions A safety campaign intervention may result in an initial (ES −1.82; 95% CI −2.90 to −0.74) and sustained (ES −1.30; 95% CI −1.79 to −0.81) decrease in injuries at the company level (1 ITS study), but not at the regional level (1 ITS study). A multifaceted drug-free workplace programme at the company level may reduce non-fatal injuries in the year following implementation by −7.6 per 100 person-years (95% CI −11.2 to −4.0) and in the years thereafter by −2.0 per 100 person-years (95% CI −3.5 to −0.5) (1 ITS study). Introducing occupational health services may result in no decrease in fatal or non-fatal injuries (one CBA study). The vast majority of interventions to adopt safety measures recommended by standard texts on safety, consultants and safety courses have not been adequately evaluated. There is very low-quality evidence that introducing regulations as such may or may not result in a decrease in fatal and non-fatal injuries. There is also very low-quality evidence that regionally oriented safety campaigns, training, inspections or the introduction of occupational health services may not reduce non-fatal injuries in construction companies. There is very low-quality evidence that company-oriented safety interventions such as a multifaceted safety campaign, a multifaceted drug workplace programme and subsidies for replacement of scaffoldings may reduce non-fatal injuries among construction workers. More studies, preferably cluster-randomised controlled trials, are needed to evaluate different strategies to increase the employers' and workers' adherence to the safety measures prescribed by regulation. | We conducted a systematic search of the literature on preventing occupational injuries among construction workers. We included 17 studies in this updated review, rating the evidence as very low quality. Multifaceted interventions and company incentives for upgrading equipment may be effective in reducing injury. However, an evidence base is still needed for the vast majority of safety measures that safety manuals, consultants and safety courses routinely recommend. What was studied in the review? We looked at different types of workplace interventions, including the introduction of new regulations, safety campaigns, training, inspections, occupational health services, and company subsidies. We evaluated the quality of the studies and the effectiveness of interventions, rating the evidence as very low quality. What are the main results of the review? Introducing regulations alone may or may not be effective for preventing non-fatal and fatal injuries in construction workers. Regionally oriented interventions such as a safety campaigns, training, inspections or occupational health services may not be effective for reducing non-fatal injuries in construction workers. However, a multifaceted safety campaign and a multifaceted drug-free workplace programme at the company level, along with subsidies for replacement of scaffoldings, may be effective in reducing non-fatal injuries. Additional strategies are needed to increase the employers' and workers' adherence to the safety measures that are prescribed by regulation. How up-to-date is this review? We searched for studies that had been published up to 1 April 2017. |
Three studies met our inclusion criteria. In one study dichlorphenamide (DCP) vs placebo was tested in two groups of participants: 42 with hypokalemic periodic paralysis (HypoPP) and 31 with hyperkalemic periodic paralysis (HyperPP), based on clinical criteria. Thirty-four of 42 participants with hypokalemic periodic paralysis completed both treatment phases. For the 34 participants having attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.02) and severity-weighted attack rate (P = 0.01) on DCP relative to placebo were statistically significant. Fifteen preferred DCP, three placebo and six their baseline medication. Twenty-four of 31 participants with hyperkalemic periodic paralysis completed both treatment phases: for the 16 participants who had attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.006) and in severity-weighted attack rate (P = 0.02) on DCP relative to placebo were significant. Fifteen preferred DCP, one placebo and five their baseline medication. Acetazolamide proved to improve muscle strength in eight participants with HypoPP in one other study and pinacidil, a potassium channel opener, also improved muscle strength in 2/4 participants with HypoPP in a third study. The largest included study that met our inclusion criteria suggested that DCP was effective in the prevention of episodic weakness in both hypokalemic and hyperkalemic periodic paralyses. The other two studies provide some evidence that either acetazolamide or pinacidil may improve muscle strength. However we still lack sufficient evidence to provide full guidelines for the treatment of people with periodic paralysis. | We found two small studies demonstrating an improvement of muscle strength with pinacidil and acetazolamide. There was only one trial considering treatment of paralytic attacks, demonstrating a decrease in the severity and frequency of the attacks using diclorophenamide. We did not find other randomised or quasi-randomised studies, but only case reports and anecdotal articles using other drugs to reduce paralyses attacks. Further research is needed to determine the best treatment for reducing the frequency and severity of attacks and to treat or prevent permanent muscle weakness. |
Twenty-eight trials with 1273 menopausal women were included in this review. Data could be extracted from 16 trials to conduct the meta-analysis. The overall quality of the studies was moderate to low with the majority of studies that were included in the meta-analysis having reasonable methodology. Compared to placebo, DHEA did not improve quality of life (standardised mean difference (SMD) 0.16, 95% confidence interval (CI) -0.03 to 0.34, P = 0.10, 8 studies, 287 women (132 from parallel and 155 from crossover trials), I² = 0%, moderate quality evidence; one trial of the nine that reported on this outcome was removed in a sensitivity analysis as it was judged to be at high risk of bias). DHEA was found to be associated with androgenic side effects (mainly acne) (odds ratio (OR) 3.77, 95% CI 1.36 to 10.4, P = 0.01, 5 studies, 376 women, I² = 10%, moderate quality evidence) when compared to placebo. No associations were found with other adverse effects. It was unclear whether DHEA affected menopausal symptoms as the results from the trials were inconsistent and could not easily be pooled to provide an overall effect due to different types of measurement (for example continuous, dichotomous, change and end scores). DHEA was found to improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55, P = 0.01, 5 studies, 261 women (239 women from parallel trials and 22 women from crossover trials), I² = 0%; one trial judged to be at high risk of bias was removed during sensitivity analysis) compared to placebo. There was no difference in the acne associated with DHEA when comparing studies that used oral DHEA (OR 2.16, 95% CI 0.47 to 9.96, P = 0.90, 3 studies, 136 women, I² = 5%, very low quality evidence) to one study that used skin application of DHEA (OR 2.74, 95% CI 0.10 to 74.87, P = 0.90, 1 study, 22 women, very low quality evidence). The effects did not differ for sexual function when studies using oral DHEA (SMD 0.11, 95% CI -0.13 to 0.35, P = 0.36, 5 studies, 340 women, I² = 0) were compared to a study using intravaginal DHEA (SMD 0.42, 95% CI 0.03 to 0.81, 1 study, 218 women). Test for subgroup differences: Chi² = 1.77, df = 1 (P = 0.18), I² = 43.4%. Insufficient data were available to assess quality of life and menopausal symptoms for this comparison. There were insufficient data available to compare the effects of DHEA to hormone therapy (HT) for quality of life, menopausal symptoms, and adverse effects. No large differences in treatment effects were found for sexual function when comparing DHEA to HT (mean difference (MD) 1.26, 95% CI -0.21 to 2.73, P = 0.09, 2 studies, 41 women, I² = 0%). There is no evidence that DHEA improves quality of life but there is some evidence that it is associated with androgenic side effects. There is uncertainty whether DHEA decreases menopausal symptoms, but DHEA may slightly improve sexual function compared with placebo. | A total of 28 randomised controlled trials were included, with a total of 1273 menopausal women. Over 95% of the study populations were postmenopausal women. Women's ages ranged from 36 to 80 years. Treatment duration varied from one week to one year. In more than 80% of the trials DHEA was administered orally with the daily doses varying between 10 mg and 1600 mg. We found no evidence that DHEA improves quality of life. There was some evidence that it was associated with androgenic side effects (for example acne, unwanted hair growth (hirsutism)). It was uncertain whether DHEA decreased menopausal symptoms, but DHEA may have slightly improved sexual function. The quality of the evidence was moderate for both quality of life and side effects. We downgraded the quality of evidence based on the lack of data on randomisation, allocation, or blinding; small study sizes overall; and limited data available. |
Forty-one trials (10,681 participants) met the inclusion criteria. Trials were grouped according to similar interventions (changes to organisation of nutritional care (N = 13; 3456 participants), changes to the feeding environment (N = 5; 351 participants), modification of meal profile or pattern (N = 12; 649 participants), additional supplementation of meals (N = 10; 6022 participants) and home meal delivery systems (N = 1; 203 participants). Follow-up ranged from ‘duration of hospital stay’ to 12 months. The overall quality of evidence was moderate to very low, with the majority of trials judged to be at an unclear risk of bias in several risk of bias domains. The risk ratio (RR) for all-cause mortality was 0.78 (95% confidence interval (CI) 0.66 to 0.92); P = 0.004; 12 trials; 6683 participants; moderate-quality evidence. This translates into 26 (95% CI 9 to 41) fewer cases of death per 1000 participants in favour of supportive interventions. The RR for number of participants with any medical complication ranged from 1.42 in favour of control compared with 0.59 in favour of supportive interventions (very low-quality evidence). Only five trials (4451 participants) investigated health-related quality of life showing no substantial differences between intervention and comparator groups. Information on patient satisfaction was unreliable. The effects of supportive interventions versus comparators on hospitalisation showed a mean difference (MD) of -0.5 days (95% CI -2.6 to 1.6); P = 0.65; 5 trials; 667 participants; very low-quality evidence. Only three of 41 included trials (4108 participants; very low-quality evidence) reported on adverse events, describing intolerance to the supplement (diarrhoea, vomiting; 5/34 participants) and discontinuation of oral nutritional supplements because of refusal or dislike of taste (567/2017 participants). Meta-analysis across 17 trials with adequate data on weight change revealed an overall improvement in weight in favour of supportive interventions versus control: MD 0.6 kg (95% CI 0.21 to 1.02); 2024 participants; moderate-quality evidence. A total of 27 trials investigated nutritional intake with a majority of trials not finding marked differences in energy intake between intervention and comparator groups. Only three trials (1152 participants) reported some data on economic costs but did not use accepted health economic methods (very low-quality evidence). There is evidence of moderate to very low quality to suggest that supportive interventions to improve nutritional care results in minimal weight gain. Most of the evidence for the lower risk of all-cause mortality for supportive interventions comes from hospital-based trials and more research is needed to confirm this effect. There is very low-quality evidence regarding adverse effects; therefore whilst some of these interventions are advocated at a national level clinicians should recognise the lack of clear evidence to support their role. This review highlights the importance of assessing patient-important outcomes in future research. | We included 41 randomised controlled studies (clinical studies where people are randomly put into one of two or more treatment groups) with a total of 10,681 people in our review. There were five different interventions which we call 'supportive interventions': changes to the organisation of nutritional care (13 studies, 3456 people), changes to the feeding environment (5 studies, 351 people), modification of the meal profile or pattern (12 studies, 649 people), additional supplementation of meals (10 studies, 6022 people) and home meal delivery systems (1 study, 203 people). Monitoring participants over time (follow-up) ranged from ‘duration of hospital stay’ to 12 months. The comparator groups received 'usual' care. More than half of all participants took part in studies investigating the additional supplementation of meals (for example a protein-energy oral nutritional supplement in addition to the usual diet). It is possible that supportive interventions for enhancing dietary intake in nutritionally vulnerable groups reduce death from any cause (approximately 23 fewer cases of death per 1000 participants in favour of supportive interventions). However, this has to be confirmed by more evidence from high-quality randomised controlled studies. The number of participants experiencing any medical complication did not differ substantially between the supportive interventions and the comparator groups. The same was found for health-related quality of life (which is physical, mental, emotional and social health attributed to health), patient satisfaction, nutritional or energy intake and days spent in hospital. Economic costs were not well investigated. Only three studies reported on side effects, describing intolerance to the nutritional supplement (such as diarrhoea or vomiting in 5 of 34 participants) and discontinuation of oral nutritional supplements because of refusal or dislike of taste (567 of 2017 participants). After analysing 15 studies in 1945 participants we found a beneficial effect of supportive interventions compared with comparators on weight: on average people in the supportive interventions groups increased their weight 0.6 kg more than people in the comparator groups. This evidence is up to date as of September 2016. The overall quality of evidence ranged between moderate to very low, mainly because for most of our outcomes there was only a small number of studies and participants to achieve reliable information, or because risk of bias made results uncertain. However, if some randomised controlled studies with low risk of bias for our patient-important outcomes and a good number of participants were performed, this review could quickly provide good guidance for better health care. |
This first update of the review identified two additional eligible studies, bringing the total number of included studies to 25 (forty seven randomised controlled comparisons involving 2543 children considered to be at normal risk of regurgitation or aspiration during anaesthesia). Only one incidence of aspiration and regurgitation was reported. Children permitted fluids up to 120 minutes preoperatively were not found to experience higher gastric volumes or lower gastric pH values than those who fasted. The children permitted fluids were less thirsty and hungry, better behaved and more comfortable than those who fasted. Clear fluids preoperatively did not result in a clinically important difference in children's gastric volume or pH. Evidence relating to the preoperative intake of milk was sparse. The volume of fluid permitted during the preoperative period did not appear to impact on children's intraoperative gastric volume or pH contents. There is no evidence that children who are denied oral fluids for more than six hours preoperatively benefit in terms of intraoperative gastric volume and pH compared with children permitted unlimited fluids up to two hours preoperatively. Children permitted fluids have a more comfortable preoperative experience in terms of thirst and hunger. This evidence applies only to children who are considered to be at normal risk of aspiration/regurgitation during anaesthesia. | However, the review of trials found that drinking clear fluids up to a few hours before surgery did not increase the risk of regurgitation during or after surgery. Indeed there is an added benefit of a more comfortable preoperative experience in terms of thirst and hunger. Some children are considered more likely to regurgitate under anaesthetic, including those who are obese or have stomach disorders. More research is needed to determine whether these children can also safely drink up to a few hours before surgery. |
We included 14 studies (747 participants). The studies included children (seven studies, 499 participants) and adults (seven studies, 248 participants). No studies reported outcomes beyond three months follow-up. Saline volumes ranged from 'very low' to 'high' volume. Where stated, studies used either hypertonic or isotonic saline solution. Nasal saline versus no saline treatment All seven studies (112 adults; 332 children) evaluating this comparison used different scoring systems for patient-reported disease severity, so we pooled the data using the standardised mean difference (SMD). Saline irrigation may improve patient-reported disease severity compared with no saline at up to four weeks (SMD -1.32, 95% confidence interval (CI) -1.84 to -0.81; 407 participants; 6 studies; low quality) and between four weeks and three months (SMD -1.44, 95% CI -2.39 to -0.48; 167 participants; 5 studies; low quality). Although the evidence was low quality the SMD values at both time points are considered large effect sizes. Subgroup analysis showed the improvement in both adults and children. Subgroup analyses for volume and tonicity were inconclusive due to heterogeneity. Two studies reported methods for recording adverse effects and five studies mentioned them. Two studies (240 children) reported no adverse effects (epistaxis or local discomfort) in either group and three only reported no adverse effects in the saline group. One study (48 children) reported disease-specific HRQL using a modified RCQ-36 scale. It was uncertain whether there was a difference between the groups at any of the specified time points (very low quality). No other secondary outcomes were reported. Nasal saline versus no saline with adjuvant use of intranasal steroids or oral antihistamines Three studies (40 adults; 79 children) compared saline with intranasal steroids versus intranasal steroids alone; one study (14 adults) compared saline with oral antihistamines versus oral antihistamines alone. It is uncertain if there is a difference in patient-reported disease severity at up to four weeks (SMD -0.60, 95% CI -1.34 to 0.15; 32 participants; 2 studies; very low quality) or from four weeks to three months (SMD -0.32, 95% CI -0.85 to 0.21; 58 participants; 2 studies; very low quality). Although none of the studies reported methods for recording adverse effects, three mentioned them: one study (40 adults; adjuvant intranasal steroids) reported no adverse effects (epistaxis or local discomfort) in either group; the other two only reported no adverse effects in the saline group. It is uncertain if saline irrigation in addition to pharmacological treatment improved disease-specific HRQL at four weeks to three months, compared with pharmacological treatment alone (SMD -1.26, 95% CI -2.47 to -0.05; 54 participants; 2 studies; very low quality). No other secondary outcomes were reported. Nasal saline versus intranasal steroids It is uncertain if there was a difference in patient-reported disease severity between nasal saline and intranasal steroids at up to four weeks (MD 1.06, 95% CI -1.65 to 3.77; 14 participants; 1 study), or between four weeks and three months (SMD 1.26, 95% CI -0.92 to 3.43; 97 participants; 3 studies), or indisease-specific HRQL between four weeks and three months (SMD 0.01, 95% CI -0.73 to 0.75; 83 participants; 2 studies). Only one study reported methods for recording adverse effects although three studies mentioned them. One (21 participants) reported two withdrawals due to adverse effects but did not describe these or state which group. Three studies reported no adverse effects (epistaxis or local discomfort) with saline, although one study reported that 27% of participants experienced local discomfort with steroid use. No other secondary outcomes were reported. Saline irrigation may reduce patient-reported disease severity compared with no saline irrigation at up to three months in both adults and children with allergic rhinitis, with no reported adverse effects. No data were available for any outcomes beyond three months. The overall quality of evidence was low or very low. The included studies were generally small and used a range of different outcome measures to report disease severity scores, with unclear validation. This review did not include direct comparisons of saline types (e.g. different volume, tonicity). Since saline irrigation could provide a cheap, safe and acceptable alternative to intranasal steroids and antihistamines further high-quality, adequately powered research in this area is warranted. | We found 14 studies with a total of 747 participants (260 adults; 487 children). The volume of saline used in the studies varied: five studies used 'very low' volumes (nasal sprays providing less than 5 mL saline per nostril per application), two studies used low-volume (between 5 and 59 mL saline per nostril per application introduced with a syringe) and four studies used high-volume solutions (more than 60 mL per nostril per application). Eight studies used hypertonic saline, five used isotonic saline and three studies did not provide this information. Two studies used two different types of saline solutions. Seven studies did not say how they were funded. The other seven were funded either by the investigators' department or research grants from regional or national government. No studies were funded by pharmaceutical companies. Nasal saline irrigation compared with no saline irrigation Nasal saline irrigation may have benefits in both adults and children in relieving the symptoms of allergic rhinitis compared to no saline irrigation and it is unlikely to be associated with adverse effects. It is not possible to tell from this review whether there is a difference between the different volumes and concentrations of saline solution. Adding nasal saline irrigation onto 'pharmacological' allergic rhinitis treatment It is uncertain whether adding nasal saline irrigation to pharmacological treatment (intranasal steroids or oral antihistamines) helps to improve the symptoms of allergic rhinitis compared to using pharmacological treatments alone. The use of nasal saline irrigation is unlikely to be associated with adverse effects. Nasal saline irrigation compared to 'pharmacological' allergic rhinitis treatment There is not enough evidence to know whether nasal saline irrigation is better, worse or the same as using intranasal steroids. No studies reporting the outcomes we were interested in compared nasal saline irrigation with oral antihistamines. The overall quality of evidence for nasal saline irrigation compared with no saline treatment was eitherlow quality (our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect) or very low quality (we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect). This was because the studies were mostly very small and used different methods to measure the same outcome. Since saline irrigation could provide a cheap, safe and acceptable alternative to intranasal steroids and antihistamines further high-quality studies are needed. |
We identified 20 randomised trials (211,818 participants), assessing beta-carotene (12 trials), vitamin A (4 trials), vitamin C (8 trials), vitamin E (10 trials), and selenium (9 trials). Trials quality was generally high. Heterogeneity was low to moderate. Antioxidant supplements were without significant effects on gastrointestinal cancers (RR 0.94, 95% CI 0.83 to 1.06). However, there was significant heterogeneity (I2 = 54.0%, P = 0.003). The heterogeneity may have been explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96 to 1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43 to 0.80; test of interaction P < 0.0005), and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). The antioxidant supplements had no significant effects on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97 to 1.07, I2 = 53.5%), but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02 to 1.07). Beta-carotene in combination with vitamin A (RR 1.16, 95% CI 1.09 to 1.23) and vitamin E (RR 1.06, 95% CI 1.02 to 1.11) significantly increased mortality. Increased yellowing of the skin and belching were non-serious adverse effects of beta-carotene. In five trials (four with high risk of bias), selenium seemed to show significant beneficial effect on gastrointestinal cancer occurrence (RR 0.59, 95% CI 0.46 to 0.75, I2 = 0%). We could not find convincing evidence that antioxidant supplements prevent gastrointestinal cancers. On the contrary, antioxidant supplements seem to increase overall mortality. The potential cancer preventive effect of selenium should be tested in adequately conducted randomised trials. | In this review prevention with antioxidant supplements of oesophageal, gastric, small intestinal, colorectal, pancreatic, liver, and biliary tract cancers is assessed. The review includes 20 randomised clinical trials. In total, 211,818 participants were randomised to antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo. Trial quality was exceptionally good. Based on properly designed and conducted randomised clinical trials, convincing evidence that beta-carotene, vitamin A, vitamin C, and vitamin E or their combinations may prevent gastrointestinal cancers is not found. A total of 2057 of 95084 participants (2.2%) randomised to antioxidant supplements and 1548 of 78935 participants (2.0%) randomised to placebo developed gastrointestinal cancers. These antioxidant supplements even seem to increase mortality. A total of 17114 of 122,501 participants (14.0%) randomised to antioxidant supplements and 8799 of 78693 participants (11.2%) randomised to placebo died. Selenium alone may have preventive effects on gastrointestinal cancers. This finding, however, is based on trials with flaws in their design and needs confirmation in properly conducted randomised clinical trials. |
We identified 11 trials that enrolled 687 eyes of 679 participants. The studies were conducted in the United States, Europe, Asia and Africa. Five studies enrolled participants at low risk of trabeculectomy failure, five studies enrolled participants at high risk of failure, and one study enrolled people with both high and low risk of failure. None of the included trials enrolled participants with combined trabeculectomy/cataract surgery. We considered one study to be at low risk of bias in all domains, six studies to be at high risk of bias in one or more domains, and the remaining four studies to be at an unclear risk of bias in all domains. The risk of failure of trabeculectomy at one year after surgery was less in those participants who received MMC compared to those who received 5-FU, however the confidence intervals were wide and are compatible with no effect (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.30 to 1.00; studies = 11; I2 = 40%). There was no evidence for any difference between groups at high and low risk of failure (test for subgroup differences P = 0.69). On average, people treated with MMC had lower intraocular pressure at one year (mean difference (MD) -3.05 mmHg, 95% CI -4.60 to -1.50), but the studies were inconsistent (I2 = 52%). The size of the effect was greater in the high-risk group (MD -4.18 mmHg, 95% CI -6.73 to -1.64) compared to the low-risk group (MD -1.72 mmHg, 95% CI -3.28 to -0.16), but again the test for interaction was not statistically significant (P = 0.11). Similar proportions of eyes treated with MMC lost 2 or more lines of visual acuity one year after surgery compared to 5-FU, but the confidence intervals were wide (RR 1.05, 95% CI 0.54 to 2.06). Adverse events occurred relatively rarely, and estimates of effect were generally imprecise. There was some evidence for less epitheliopathy in the MMC group (RR 0.23, 95% CI 0.11 to 0.47) and less hyphaema in the MMC group (RR 0.62, 95% CI 0.42 to 0.91). None of the studies reported quality of life. Overall, we graded the quality of the evidence as low largely because of risk of bias in the included studies and imprecision in the estimate of effect. We found low-quality evidence that MMC may be more effective in achieving long-term lower intraocular pressure than 5-FU. Further comparative research on MMC and 5-FU is needed to enhance reliability and validity of the results shown in this review. Furthermore, the development of new agents that control postoperative scar tissue formation without side effects would be valuable and is justified by the results of this review. | We included 11 randomised controlled trials conducted in the United States, Europe, Asia and Africa in this review. In total, 687 eyes of 679 participants underwent routine trabeculectomy for glaucoma control. Some participants were at a higher risk of failure than others, for example if they had had previous glaucoma surgery, were of African origin, or if they had secondary glaucoma. Five studies enrolled participants at low risk of trabeculectomy failure, five studies enrolled participants at high risk of failure, and one study enrolled people with both high and low risk of failure. None of the included trials enrolled participants with combined trabeculectomy/cataract surgery. Our review showed that the risk of failure of trabeculectomy at one year after surgery was slightly less in those participants treated with MMC compared to 5-FU. All of the included randomised controlled trials contributed to this result, with a mixed study population of high- and low-risk participants and varied methodology of antimetabolite application. We did not detect any significant differences between the subgroups of participants at low and high risk of failure, but the power of this analysis was low. We identified no difference between the visual outcomes of the group that received MMC and the group that received 5-FU at one year postoperatively nor in the number of drops used postoperatively. However, we found evidence to suggest that MMC was more effective at lowering intraocular pressure than 5-FU in both high- and low-risk participants, achieving a lower mean intraocular pressure postoperatively than in those who were treated with 5-FU at one year. This effect seemed to be greater in the high-risk populations. Evaluating the overall complications across all studies revealed a slight favour toward using MMC, particularly with the incidence of epitheliopathy and hyphaema. There was a trend towards bleb leaks, wound leaks, late hypotony and cataract formation in the MMC-treated group. None of the studies reported quality of life. We graded the quality of the evidence as low, mostly due to the risk of bias in the included studies. One bias we commonly encountered came from the different techniques of antimetabolite administration, making it difficult to conceal which medicine was being used. Furthermore, most studies only had a few complications to report, which meant that there were low numbers overall to include in the analysis of complications. |
The comprehensive searches found one randomised controlled trial of treatment for amphetamine psychosis meeting the criteria for considering studies. The study involved 58 participants and compared the efficacy and tolerability of two antipsychotic drugs, olanzapine (a newer antipsychotic) and haloperidol (a commonly used antipsychotic medication used as a control condition), in treating amphetamine-induced psychosis. The results show that both olanzapine and haloperidol at clinically relevant doses were efficacious in resolving psychotic symptoms, with the olanzapine condition showing significantly greater safety and tolerability than the haloperidol control as measured by frequency and severity of extrapyramidal symptoms. Only one RCT of treatment for amphetamine psychosis has been published. Outcomes from this trial indicate that antipsychotic medications effectively reduce symptoms of amphetamine psychosis, the newer generation and more expensive antipsychotic medication, olanzapine, demonstrates significantly better tolerability than the more affordable and commonly used medication, haloperidol. There are other two studies that did not meet the inclusion criteria for this review. The results of these two studies show that agitation and some psychotic symptoms may be abated within an hour after antipsychotic injection. Whether this limited evidence can be applied for amphetamine psychotic patients is not yet known. The medications that should be further investigate are conventional antipsychotics, newer antipsychotics and benzodiazepines. However, naturalistic studies of amphetamine psychotic symptoms and the prevalence of relapse to psychosis in the presence of amphetamine, are also crucial for advising the development of study designs appropriate for further treatment studies of amphetamine psychosis. | In one of the only randomised trials of antipsychotic medications for treating amphetamine psychosis, Leelahanaj (2005) reported that olanzapine and haloperidol delivered at clinically relevant doses both showed similar efficacy in resolving psychotic symptoms (93% and 79%, respectively), with olanzapine showing significantly greater safety and tolerability than haloperidol as measured by frequency and severity of extrapyramidal symptoms. These outcomes are consistent with treatments for schizophrenia indicating equivalent efficacy between atypical anti-psychotics and conventional anti-psychotics, mostly haloperidol with older drugs causing more severe side effects (Leucht 1999).While anti-psychotic medications demonstrate efficacy in providing short-term relief when a heavy user of amphetamines experiences psychosis, there is no evidence to guide decisions regarding long-term clinical care using these medications for preventing relapse to psychosis. |
We excluded five studies that were not RCTs. There were no eligible trials for inclusion in this review. There is currently a lack of RCT evidence regarding the effectiveness of interventions for investigating and identifying the causes of stillbirth. Seeking to determine the causes of stillbirth is an essential component of quality maternity care, but it remains unclear what impact these interventions have on the psychosocial outcomes of parents and families, the rates of diagnosis of the causes of stillbirth, and the care and management of subsequent pregnancies following stillbirth. Due to the absence of trials, this review is unable to inform clinical practice regarding the investigation of stillbirths, and the specific investigations that would determine the causes. Future RCTs addressing this research question would be beneficial, but the settings in which the trials take place, and their design, need to be given careful consideration. Trials need to be conducted with the utmost care and consideration for the needs, concerns, and values of parents and families. Assessment of longer-term psychosocial variables, economic costs to health services, and effects on subsequent pregnancy care and outcomes should also be considered in any future trials. | We searched for evidence on 15 May 2017. We did not find any trials for inclusion in this review. We excluded five trials because they were not randomised controlled trials. There is no evidence available to guide how best to investigate the causes of stillbirth. Seeking to determine the causes of a baby's death is an essential component of quality maternity care in any setting. Future trials on this topic would be helpful, but such trials would need to be designed in a way that ensures all parents in the trial still receive the minimum standard of care in their local setting. Future trials would need to be conducted with the utmost care and consideration for the needs, concerns, and values of parents and families. Assessment of longer-term psychosocial variables, economic costs to health services, and effects on subsequent pregnancy care and outcomes should be considered in any future trials. |
We found two small randomised controlled trails that fulfilled the eligibility criteria (Corbet 1977; Dixon 1999) and one unpublished pilot trial (Lawn 2005). Corbet 1977 compared treating infants with sodium bicarbonate infusion (N = 30) versus no treatment (N = 32) and did not find evidence of an effect on mortality [relative risk (RR) 1.39 (95% confidence interval 0.72 to 2.67)] or in the incidence of intra/periventricular haemorrhage [RR 1.24 (95% confidence interval 0.47 to 3.28)]. Addition of the unpublished data of Lawn 2005 does not change the overall estimate of effect on mortality [typical RR 1.45 (95%CI 0.82 to 2.56)]. Dixon 1999 compared treatment with sodium bicarbonate (N = 16) versus fluid bolus (N = 20). The primary outcome assessed was arterial blood pH/base excess two hours after the intervention. Other clinical outcomes were not reported. Neither trial assessed longer term neurodevelopmental outcomes. There is insufficient evidence from randomised controlled trials to determine whether infusion of base or fluid bolus reduces morbidity and mortality in preterm infants with metabolic acidosis. Further large randomised trials are needed. | The review authors searched the medical literature and found two small randomised controlled trials (98 infants) measuring/investigating the benefit of either infusion of base or of a fluid injection (bolus) in the treatment of preterm infants with metabolic acidosis. Infants were given an infusion of sodium bicarbonate on the first day of postnatal life, compared with no treatment or a fluid bolus with albumin. There was no clear evidence that the base infusion corrected metabolic acidosis more effectively. One of the studies (62 newborns) reported no difference in early deaths at one week or in the incidence of bleeding in the brain. Neither study assessed longer-term neurological disabilities. |
We included seven trials involving 500 participants that studied the effect of hyaluronidase on intraoperative pain. Four of the seven trials with 289 participants reported the primary outcome in a dichotomous manner, and we proceeded to meta-analyse the findings which showed a moderate heterogeneity that could not be explained (I2 = 41% ). The pooled risk ratio (RR) for these four trials was 0.83 with the 95% confidence interval ranging from 0.48 to 1.42. The reduction in intraoperative pain scores in the hyaluronidase group were not statistically significant. Among the three trials that reported the primary outcome in a continuous manner, the presence of missing data made it difficult to conduct a meta-analysis. To further explore the data, we imputed standard deviations for the other studies from another included RCT (Sedghipour 2012). However, this resulted in substantial heterogeneity between study estimates (I² = 76% ). The lack of reported relevant data in two of the three remaining trials made it difficult to assess the direction of effect in a clinical setting. Overall, there was no statistical difference regarding the intraoperative reduction of pain scores between the hyaluronidase and control group. All seven included trials had a low risk of bias. According to GRADE, we found the quality of evidence was low and downgraded the trials for serious risk of inconsistency and imprecision. Therefore, the results should be analysed with caution. Participant satisfaction scores were significantly higher in the hyaluronidase group in two high quality trials with 122 participants. Surgical satisfaction was also superior in two of three high quality trials involving 141 participants. According to GRADE, the quality of evidence was moderate for participant and surgical satisfaction as the trials were downgraded for imprecision due to the small sample sizes. The risk of bias in these trials was low. There was no reported harm due to the addition of hyaluronidase in any of the studies. No study reported on the cost of hyaluronidase in the context of eye surgery. The effects of adding hyaluronidase to local anaesthetic fluid on pain outcomes in people undergoing eye surgery are uncertain due to the low quality of evidence available. A well designed RCT is required to address inconsistency and imprecision among the studies and to determine the benefit of hyaluronidase to improve analgesia during eye surgery. Participant and surgical satisfaction is higher with hyaluronidase compared to the control groups, as demonstrated in moderate quality studies. There was no harm attributed to the use of hyaluronidase in any of the studies. Considering that harm was only rarely defined as an outcome measure, and the overall small number of participants, conclusions cannot be drawn about the incidence of harmful effects of hyaluronidase. None of the studies undertook cost calculations with regards to use of hyaluronidase in local anaesthetic eye blocks. | We included seven randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) in our review. These involved 500 adults undergoing eye surgery under local anaesthesia. We looked at any additional effect of adding hyaluronidase to local anaesthetic on the pain experienced during eye surgery. We also looked at participant and surgical satisfaction scores and if any harms were reported after using hyaluronidase in the injection solution. None of the studies reported on costs. Of the seven included trials, we pooled the results of four trials (289 participants) as the results were reported in a similar manner. They found that addition of hyaluronidase did not significantly reduce pain during surgery. Among the three remaining trials (211 participants) lack of data reporting in two trials made it difficult to pool the results. The overall result of looking at all these trials together suggests there was no significant reduction of pain with using hyaluronidase in eye nerve blocks. We found moderate quality evidence from two trials (122 participants) to suggest that addition of hyaluronidase increased participant satisfaction scores. Three studies involving 141 participants looked at surgical satisfaction, which was reported as superior with hyaluronidase in the two larger studies and not significantly different in one small study (19 participants). None of the included studies reported any harmful effects of hyaluronidase. The included trials that reported on pain during surgery were at low risk for bias. The overall quality of evidence was low because of variations in the effect on pain reduction. We contacted all trial authors to request more information on the trials, but the data were not available. Moderate quality studies reported greater participant and surgical satisfaction with hyaluronidase. Analgesia alone does not take into account the full spectrum of the beneficial effects of hyaluronidase. Patient comfort with the eye surgery is also likely to be improved by a speedy onset and reduced eye movements due to hyaluronidase. |
Fifty-eight community coalition-driven intervention studies were included. No study was considered to be at low risk of bias. Behavioral change outcomes and health status change outcomes were analyzed separately. Outcomes are grouped by intervention type. Pooled effects across intervention types are not presented because the diverse community coalition-led intervention studies did not examine the same constructs or relationships, and they used dissimilar methodological designs. Broad-scale community system level change strategies led to little or no difference in measures of health behavior or health status (very low-certainty evidence). Broad health and social care system level strategies leds to small beneficial changes in measures of health behavior or health status in large samples of community residents (very low-certainty evidence). Lay community health outreach worker interventions led to beneficial changes in health behavior measures of moderate magnitude in large samples of community residents (very low-certainty evidence). Lay community health outreach worker interventions may lead to beneficial changes in health status measures in large samples of community residents; however, results were not consistent across studies (low-certainty evidence). Group-based health education led by professional staff resulted in moderate improvement in measures of health behavior (very low-certainty evidence) or health status (low-certainty evidence). Adverse outcomes of community coalition-led interventions were not reported. Coalition-led interventions are characterized by connection of multi-sectoral networks of health and human service providers with ethnic and racial minority communities. These interventions benefit a diverse range of individual health outcomes and behaviors, as well as health and social care delivery systems. Evidence in this review shows that interventions led by community coalitions may connect health and human service providers with ethnic and racial minority communities in ways that benefit individual health outcomes and behaviors, as well as care delivery systems. However, because information on characteristics of the coalitions themselves is insufficient, evidence does not provide an explanation for the underlying mechanisms of beneficial effects. Thus, a definitive answer as to whether a coalition-led intervention adds extra value to the types of community engagement intervention strategies described in this review remains unattainable. | This review, which included searches of databases from January 1990 through March 31, 2014, found 58 community coalition-driven studies, which addressed a wide array of health outcomes and risk behaviors. Only studies of community coalitions with at least one racial or ethnic minority group representing the target population and at least two community-based public or private organizations were included. This review examined the effects of four types of strategies or interventions used by community coalitions. Community system-level change strategies (such as initiatives targeting physical environments like housing, green spaces, neighborhood safety, or regulatory processes and policies) have produced small inconsistent effects; broad health and social care system-level strategies (such as programs targeting behavior of staff in a health or social care system, accessibility of services, or policies, procedures, and technologies designed to improve quality of care) have had consistently positive small effects; interventions that used lay community health outreach workers or group-based health education led by professional staff have produced fairly consistent positive effects; and group-based health education led by peers has had inconsistent effects. This review shows that interventions led by community coalitions may connect health and human service providers with ethnic and racial minority communities in ways that benefit individual health outcomes and behaviors, as well as care delivery systems. However, to achieve the same levels of health across communities, regardless of race or ethnicity, we need to know specifically how a program does or does not work. This will require better information on how some programs described in this review brought about beneficial change and theresources needed, so they can be replicated. Furthermore, we need better scientific tools to improve our ability to identify effects of programs on whole community systems and to understand the leverage points that, when employed appropriately, shift the distribution of health toward equity. |
We included 15 studies. The total number of participants included in the analyses was 3520. Most studies were small with fewer than 120 participants, although two larger studies with 2012 and 671 participants were included. There was considerable variation in many of the study characteristics, including the anaesthetics used. The concentrations of nitrous oxide varied between 50% and 70%, and half of the studies used clinical signs and haemodynamic changes to monitor depth of anaesthesia. As it was not possible to blind the anaesthetist to the anaesthetic used, we rated all studies at high risk of performance bias and we therefore downgraded the quality of evidence by one level for risk of bias using the GRADE approach. Other types of bias were generally low, or were rated unclear due to missing information. No studies were designed to measure AAGA as the primary outcome, and were therefore statistically underpowered to answer this review question. Despite the inclusion of 3520 participants, only three awareness events were reported by two studies. In one study the event was due to technical failure. Due to the rarity of the events, we did not consider it appropriate to pool the data, and we therefore downgraded the quality of evidence by a further level for imprecision using GRADE. It is not possible to draw any conclusions from this review. The included studies were mainly small (fewer than 120 participants) and there were limited estimates of effect, with only two studies reporting any events. We cannot therefore determine whether the use of nitrous oxide in general anaesthesia increases, decreases or has no effect on the risk of accidental awareness. | We included 15 studies. The studies covered 3520 people. Although most studies were small with fewer than 120 participants, there were two larger studies with 2012 and 671 participants included. There was a great variation in many of the important elements among the studies, including the type of anaesthetics used and the levels of nitrous oxide used. No study was designed to measure accidental awareness, but rather they measured it as a secondary outcome. Although there were 3520 participants included in the studies, there were only three reports of a participant becoming aware. These were reported in two studies, and one was thought to be due to an error in the anaesthetic procedure. Nine studies reported where the funds for the research were obtained. Two were funded by pharmaceutical companies, suggesting a potential bias, whereas five were funded through Universities or Government health research grants or a charity, limiting the risk of bias. The remaining two studies reported that there was no conflict of interest, also reducing the risk of bias in these studies. Due to safety issues, all of the anaesthetists had to know what anaesthesia was being used. However, this means that the study results may have been biased. Other indicators suggested a low risk of bias, or an unclear risk because of missing information. The quality of the evidence is also low due to the lack of reports of a participant becoming aware. It is not possible to draw any conclusions from this review. The included studies were mainly too small, and only two studies reported any events. The review question is inadequately supported by the lack of strong evidence. The effect of nitrous oxide is hardly observed due to the small sample size. |
When compared to placebo, misoprostol (400-600 µg given vaginally or sublingually), gemeprost, mifepristone (200 or 600 mg), prostaglandin E and F2α (2.5 mg administered intracervically) demonstrated larger cervical preparation effects. When misoprostol was compared to gemeprost, misoprostol was more effective in preparing the cervix and was associated with fewer gastrointestinal side-effects. For vaginal administration, administration 2 hours prior was less effective than administration 3 hours prior to the abortion. Compared to oral misoprostol administration, the vaginal route was associated with significantly greater initial cervical dilation and lower rates of side-effects; however, sublingual administration 2-3 hours prior to the procedure demonstrated cervical effects superior to vaginal administration. When misoprostol (600 µg oral or 800 µg vaginal) was compared to mifepristone (200 mg administered 24 hours prior to procedure), misoprostol had inferior cervical preparatory effects. Compared to day-prior laminaria tents, 200 or 400 µg vaginal misoprostol showed no differences in the need for further mechanical dilation or length of the procedure; similarly, the osmotic dilators Lamicel and Dilapan showed no differences in cervical ripening when compared to gemeprost, although gemeprost had cervical effects which were superior to laminaria tents. Older prostaglandin regimens (sulprostone, prostaglandin E2 and F2α) were associated with high rates of gastrointestinal side-effects and unplanned pregnancy expulsions. Few studies reported women's satisfaction with cervical preparatory techniques. Modern methods of cervical ripening are generally safe, although efficacy and side-effects between methods vary. Reports of adverse events such as cervical laceration or uterine perforation are uncommon overall in this body of evidence and no published study has investigated whether cervical preparation impacts these rare outcomes. Cervical preparation decreases the length of the abortion procedure; this may become increasingly important with increasing gestational age, as mechanical dilation at later gestational ages takes longer and becomes more difficult. These data do not suggest a gestational age where the benefits of cervical dilation outweigh the side-effects, including pain, that women experience with cervical ripening procedures or the prolongation of the time interval before procedure completion. Mifepristone 200 mg, osmotic dilators and misoprostol, 400µg administered either vaginally or sublingually, are the most effective methods of cervical preparation. | This review found that cervical preparation decreased the length of time necessary for an abortion procedure, but did not seem to decrease rates of uncommon abortion complications. The medication called misoprostol worked better with less side-effects than other similar medications. Misoprostol is most effective with the least side-effects when placed in the vagina, but when placed under the tongue it is equally effective. Another drug called mifepristone worked better than misoprostol; however, it is more expensive to use. All methods of preparation take at least 2-3 hours or more to work. The review could not determine whether women preferred one method best. |
We included three trials in this review, involving 134 patients who were 60 years of age or younger. The time window for the intervention was 30 hours from stroke onset in two studies and 96 hours in one study. All trials were stopped early. Surgical decompression reduced the risk of death at the end of follow-up (OR 0.19, 95% CI 0.09 to 0.37) and the risk of death or disability defined as mRS > 4 at 12 months (OR 0.26, 95% CI 0.13 to 0.51). Death or disability defined as mRS > 3 at the end of follow-up was no different between the treatment arms (OR 0.56, 95% CI 0.27 to 1.15). Surgical decompression lowers the risk of death and death or severe disability defined as mRS > 4 in selected patients 60 years of age or younger with a massive hemispheric infarction and oedema. Optimum criteria for patient selection and for timing of decompressive surgery are yet to be defined. Since survival may be at the expense of substantial disability, surgery should be the treatment of choice only when it can be assumed, based on their preferences, that it is in the best interest of patients. Since all the trials were stopped early, an overestimation of the effect size cannot be excluded. | Results from recent clinical trials showed that surgery reduced the risk of death. However, survivors were left with moderate to severe disability requiring help in their daily life activities. These results only apply to people 60 years of age or younger. |
We identified three trials with high risk of bias which compared veno-venous bypass (n = 65) versus no veno-venous bypass (n = 66). None of the trials reported patient or graft survival. There were no significant differences regarding renal failure or blood transfusion requirements between the two groups. None of the trials reported on the morbidity related to veno-venous bypass or the requirement of veno-venous bypass in the control group. We identified one trial with high risk of bias which compared percutaneous (n = 20) versus open technique (n =19) of veno-venous bypass. The patient or graft survival was not reported. There was no difference in veno-venous bypass related morbidity between the two groups. The operating time was significantly shorter in the percutaneous technique group (MD -59 minutes; 95% CI -102 to -16). There is no evidence to support or refute the use of veno-venous bypass in liver transplantation. There is no evidence to prefer any particular technique of veno-venous bypass in liver transplantation. | We systematically searched various medical databases to determine whether veno-venous bypass is required routinely during liver transplantation. We identified a total of three randomised clinical trials with high risk of systematic error and high risk of random errors which compared veno-venous bypass (n = 65) with no veno-venous bypass (n = 66). None of the trials reported patient or graft survival. There were no differences regarding kidney failure or blood transfusion requirements between the two groups. None of the trials reported on the complications related to veno-venous bypass or the requirement of veno-venous bypass in the control group. We also identified one trial with high risk of systematic error and high risk of random errors which compared needle technique (percutaneous approach) (n = 20) with open technique (n =19) of veno-venous bypass. The patient or graft survival was not reported in this trial. There was no difference in veno-venous bypass related complications between the two groups. The operating time was shorter in the percutaneous technique group. There is currently no evidence to support the routine use of veno-venous bypass in liver transplantation. |
We included 13 articles reporting on nine studies with nine interventions. Four studies with 407 participants evaluated post-treatment programmes and five studies with 1113 participants evaluated exercise as a treatment modality. Four studies had a low risk of bias, one study a high risk and the remainder an unclear risk of bias. We found moderate quality evidence that post-treatment exercises were more effective than no intervention for reducing the rate of recurrences at one year (Rate Ratio 0.50; 95% Confidence Interval 0.34 to 0.73). There was moderate quality evidence that the number of recurrences was significantly reduced in two studies (Mean Difference -0.35; 95% CI -0.60 to -0.10) at one-half to two years follow-up. There was very low quality evidence that the days on sick leave were reduced by post-treatment exercises (Mean Difference -4.37; 95% CI -7.74 to -0.99) at one-half to two years follow-up. We found conflicting evidence for the effectiveness of exercise treatment in reducing the number of recurrences or the recurrence rate. There is moderate quality evidence that post-treatment exercise programmes can prevent recurrences of back pain but conflicting evidence was found for treatment exercise. Studies into the validity of measurement of recurrences and the effectiveness of post-treatment exercise are needed. | There were nine studies with 1520 participants. There was moderate quality evidence that post-treatment exercises can reduce both the rate and the number of recurrences of back pain. However, the results of exercise treatment studies were conflicting. Adverse (side) effects of exercising were not mentioned in any of the studies. Limitations of this review include the difference in exercises across studies, thus making it difficult to specify the content of such a programme to prevent back pain recurrences. |
Five RCTs involving a total of 687 participants with a range of clinical indications were included. No new studies were included in this update. In one three-pronged study, vessel patency was greater with intra-arterial recombinant tissue plasminogen activator (rt-PA) than with intra-arterial streptokinase (P < 0.04) or intravenous rt-PA (P < 0.01). In participants with peripheral arterial occlusion there was no statistically significant difference in limb salvage at 30 days with either urokinase or rt-PA, though this may reflect the small numbers in the studies. Incidences of haemorrhagic complications varied with fibrinolytic regime but there was no statistically significant difference between intra-arterial urokinase and intra-arterial rt-PA. In the three-pronged study intravenous rt-PA and intra-arterial streptokinase were associated with a significantly higher risk of haemorrhagic complications than with intra-arterial rt-PA (P < 0.05). There is some evidence to suggest that intra-arterial rt-PA is more effective than intra-arterial streptokinase or intravenous rt-PA in improving vessel patency in people with peripheral arterial occlusion. There was no evidence that rt-PA was more effective than urokinase for patients with peripheral arterial occlusion and some evidence that initial lysis may be more rapid with rt-PA, depending on the regime. Incidences of haemorrhagic complications were not statistically significantly greater with rt-PA than with other regimes. However, all of the findings come from small studies and a general paucity of results means that it is not possible to draw clear conclusions. | This review found some evidence from five randomized controlled trials, involving a total of 687 patients that suggested local infusion of a drug into the affected artery is more effective than infusion into a vein, and is also associated with a lower risk of unwanted bleeding. No particular drug was more effective in preventing limb loss or death than another. The drugs investigated were streptokinase, urokinase, recombinant tissue plasminogen activator and pro-urokinase. More research is needed to confirm these findings. All of the findings of this review came from small studies that involved people with peripheral arterial ischaemia of differing severity. |
We included three multifaceted and six monofaceted intervention studies (3271 children). Physician diagnosed asthma in children less than five years, and asthma as defined by respiratory symptoms and lung function criteria in children aged five years and older, both favoured treatment with a multifaceted intervention compared to usual care (< 5 years: odds ratio (OR) 0.72, 95% confidence interval (CI) 0.54 to 0.96, and > 5 years: OR 0.52, 95% CI 0.32 to 0.85). However, there was no significant difference in outcome between monofaceted intervention and control interventions (< 5 years: OR 1.12, 95% CI 0.76 to 1.64, and > 5 years: OR 0.83, 95% CI 0.59 to 1.16). Indirect comparison between these treatments did not demonstrate a significant difference between multiple interventions and mono-interventions in reducing the frequency of asthma diagnosis in children under five years (relative OR 0.64 (95% CI 0.40 to 1.04, P = 0.07) or five years and older (relative OR 0.63, 95% CI 0.35 to 1.13, P = 0.12). There was also no significant difference between either mono- and multifaceted intervention and control in reducing the likelihood of symptoms of nocturnal coughing at follow up. Wheezing, however, showed a significant difference between multifaceted and mono-interventions (relative OR 0.59, 95% CI 0.35 to 0.99, P = 0.04), but the significance was lost when data on treatment only was analysed. The available evidence suggests that the reduction of exposure to multiple allergens compared to usual care reduces the likelihood of a current diagnosis of asthma in children (at ages < 5 years and 5 years and older). Mono-intervention studies have not produced effects which are statistically significant compared with control. In children who are at risk of developing childhood asthma, multifaceted interventions, characterised by dietary allergen reduction and environmental remediation, reduce the odds of a physician diagnosis of asthma later in childhood by half. This translates to a number needed to treat (NNT) of 17. The effect of multi-faceted interventions on parent reported wheeze was inconsistent and had no significant impact on nocturnal coughing or dyspnoea. Data from monofaceted intervention exposed children studies were not significantly different from those of control groups for all outcomes. There remains uncertainty as to whether multiple interventions are more effective than mono-component interventions. The comparisons made were indirect, making the conclusions drawn uncertain. To our knowledge there are no ongoing studies in which both intervention strategies are randomly compared. The findings, however, warrant further direct comparison between multiple- and monofaceted interventions aimed at reducing the prevalence of asthma in children. | This review asks whether the risk of developing asthma, which is a disease caused by many factors, can be decreased by reducing single allergen levels in children with genetic susceptibility, or whether the reduction of more than one type of allergen exposure simultaneously will lead to a better outcome. As a direct comparison could not be made using current research we made indirect comparisons using trials that had compared single or multiple interventions with a control. In children who are at risk of developing childhood asthma 'multifaceted' interventions, which involve both dietary allergen reduction and environmental change to reduce exposure to inhaled allergens, reduce the odds of a doctor diagnosing asthma later in childhood by half. However, the effect of these multifaceted interventions on wheeze reported by parents was inconsistent and there was no beneficial effect on night-time coughing or breathlessness. Single ('monofaceted') interventions were not significantly more effective than controls in the reduction of all outcomes, but there remains uncertainty as to whether multiple interventions are more effective than single component interventions. |
There were 15 trials with 11 included in the meta-analysis. Five trials showed relaxation reduced self-reported depression compared to wait-list, no treatment, or minimal treatment post intervention (SMD -0.59 (95% CI -0.94 to -0.24)). For clinician-rated depression, two trials showed a non-significant difference in the same direction (SMD -1.35 (95% CI -3.06 to 0.37)). Nine trials showed relaxation produced less effect than psychological (mainly cognitive-behavioural) treatment on self-reported depression (SMD = 0.38 (95% CI 0.14 to 0.62)). Three trials showed no significant difference between relaxation and psychological treatment on clinician-rated depression at post intervention (SMD 0.29 (95% CI -0.18 to 0.75)). Inconsistent effects were found when comparing relaxation training to medication and there were few data available comparing relaxation with complementary and lifestyle treatments. Relaxation techniques were more effective at reducing self-rated depressive symptoms than no or minimal treatment. However, they were not as effective as psychological treatment. Data on clinician-rated depressive symptoms were less conclusive. Further research is required to investigate the possibility of relaxation being used as a first-line treatment in a stepped care approach to managing depression, especially in younger populations and populations with subthreshold or first episodes of depression. | The review of 15 trials found that it was better than no treatment or minimal treatment, but not as effective as psychological therapies like cognitive-behaviour therapy. Relaxation techniques have potential as a simple first-line psychological treatment for depression. Those who do not respond within a set time could be offered more complex psychological treatment such as cognitive-behaviour therapy. |
We included 16 studies with a total of 1146 participants in the meta-analysis. Only one study including 52 participants had a low risk of bias and low applicability concern in the patient selection domain. The median pre-test probability of unresectable disease after CT scanning across studies was 41.4% (that is 41 out of 100 participants who had resectable cancer after CT scan were found to have unresectable disease on laparotomy). The summary sensitivity of diagnostic laparoscopy was 64.4% (95% confidence interval (CI) 50.1% to 76.6%). Assuming a pre-test probability of 41.4%, the post-test probability of unresectable disease for participants with a negative test result was 0.20 (95% CI 0.15 to 0.27). This indicates that if a person is said to have resectable disease after diagnostic laparoscopy and CT scan, there is a 20% probability that their cancer will be unresectable compared to a 41% probability for those receiving CT alone. A subgroup analysis of people with pancreatic cancer gave a summary sensitivity of 67.9% (95% CI 41.1% to 86.5%). The post-test probability of unresectable disease after being considered resectable on both CT and diagnostic laparoscopy was 18% compared to 40.0% for those receiving CT alone. Diagnostic laparoscopy may decrease the rate of unnecessary laparotomy in people with pancreatic and periampullary cancer found to have resectable disease on CT scan. On average, using diagnostic laparoscopy with biopsy and histopathological confirmation of suspicious lesions prior to laparotomy would avoid 21 unnecessary laparotomies in 100 people in whom resection of cancer with curative intent is planned. | We performed a thorough literature search to identify studies published up to 15 May 2016. We identified 16 studies reporting information on 1146 people with pancreatic or periampullary cancers which were considered to be eligible for potentially curative surgery based on CT scan staging. These studies evaluated diagnostic laparoscopy and compared results of the procedure with the eventual diagnosis by the surgeon that the cancer was not resectable during major abdominal operation or examination under microscope. All of the studies were of unclear or low methodological quality in one or more aspects, which may undermine the validity of our findings. Of those people with what CT suggests seems to be a potentially surgically curable cancer, the percentage in whom more extensive cancer was found on further staging with diagnostic laparoscopy or laparotomy ranged between 17% and 82% across studies. The median percentage of people in whom cancer spread was not detected by CT scan was 41%. Adding staging laparoscopy to CT scan might decrease the number of people with unremovable disease undergoing unnecessary major operations to 20% compared to those who undergo unnecessary major operation after CT scan alone (41%). This means that using diagnostic laparoscopy could halve the rate of unnecessary major open operations in people undergoing major surgery for potentially surgically curable pancreatic cancer. |
There are now 30 studies involving 6334 participants (6339 fractures) included in this review, which was published in 2011. There was considerable variation in the quality of trial methodology and generally inadequate reporting of methods and trial findings. Allocation concealment was confirmed in one trial only. The main outcome measures reported were fracture healing complications, re-operations and mortality. The reporting of functional outcomes was particularly poor. Few trials tested the same comparison. Most of the results for the 25 separate comparisons, frequently tested within one trial only, showed no statistically significant differences between the two implants under test. It was noted that the more rare findings of favourable results were often for implants developed within the same institutions as the trial. There was a consistent finding of less avascular necrosis with the sliding hip screw in comparison with five different types of cancellous screws but there was no significant difference found for re-operations. Additionally, the sliding hip screw was found to take longer to insert and to have an increased operative blood loss compared with multiple screws or pins. No clear conclusions can be made on the choice of implant for internal fixation of intracapsular fractures from the available evidence within randomised trials. | This review of randomised controlled trials included 30 studies involving more than 6000 participants. Most of the trials were poorly reported and had flaws in their methods that could have affected their results. Few trials tested the same comparison. Most of the results for the 25 separate comparisons, frequently tested within one trial only, failed to show that one implant was better than the other under comparison. There was a consistent finding of one serious complication (avascular necrosis) with the sliding hip screw in comparison with five different types of cancellous screws. However, this was not reflected in a decrease in re-operations for this group. Additionally, the sliding hip screw was found to take longer to insert and to have an increased operative blood loss compared with multiple screws or pins. This review found no evidence from trials undertaken so far that there were any major differences between different implants in patient survival or complications related to the operation. |
One study fulfilled inclusion criteria involving 113 children randomised to an asthma education programme involving an IHW, compared to a similar education programme without an IHW. Eighty eight of these children completed the trial. Parents' asthma knowledge score (mean difference (MD) (7.49; 95% CI 5.52 to 9.46), parents' asthma skill score (MD 0.98; 95% CI 0.52 to 1.44) and days absent from school (100% school-aged children in the intervention group missed <7 days, 21% of controls missed 7-14 days, difference = 21%, 95% CI 5-36%) were significantly better in the intervention group compared to controls. There was no significant difference in mean number of exacerbations (per year) between groups. There was no difference in quality of life or children's asthma skill score; both were limited to one study only and the direction favoured IHW group. There were no studies in adults. The involvement of IHW in asthma programs targeted for their own ethnic group in one small trial was beneficial in improving most, but not all asthma outcomes in children with asthma. It is very likely that involvement of an IHW is beneficial. However as exacerbation frequency was not significantly different between groups, we cannot be confident of the results in all settings. Nevertheless, given the complexity of health outcomes and culture as well as the importance of self-determination for indigenous peoples, the practice of including IHW in asthma education programs for indigenous children and adults with asthma is justified, but should be subject to further randomised controlled trials. | In this review, we examined if involvement of an indigenous healthcare worker (IHW) (when compared to absence of an IHW) in asthma education programs improves asthma related outcomes in Indigenous children and adults with asthma. There was only one study involving 113 people eligible for inclusion in this review. The participants showed improvement in the patient's asthma knowledge score, the parent's asthma skill score and a reduction in the number of days missed from school in children who were cared for by an indigenous healthcare worker. However as exacerbation frequency was not reduced and there was only a single, small study, we cannot be confident of the results although we think it is likely that the involvement of IHW is beneficial. Nevertheless, given the complexity of health outcomes and culture as well as the importance of self-determination for indigenous peoples, the practice of including IHW in asthma education programs for indigenous children and adults with asthma is justified, but should be subject to further randomised controlled trials |
We included one trial reporting outcome at follow-up times ranging between two and 47 months for 81 participants with Mason type 1 and 2 radial head fractures. This poorly-reported trial was at particular high risk of detection and reporting biases. The trial found no significant differences between early and delayed mobilisation in the numbers of participants with pain or limitations in their range of elbow motion. All participants were reported as being able to use their arms for full activities of daily living and none had changed their occupation or lifestyle. There was no mention of fracture complications. There is a lack of robust evidence to inform on the timing of mobilisation, and specifically on the use of early mobilisation, after non-surgical or surgical treatment for adults with elbow fractures. There is a need for high quality, well-reported, adequately powered, randomised controlled trials that compare early versus delayed mobilisation in people with commonly-occurring elbow fractures, treated with or without surgery. Trials should use validated upper limb function scales, and assessment should be both short-term (to monitor recovery and early complications) and long-term (at least one year). | We searched for randomised controlled trials that compared early movement with delayed movement of the elbow after elbow fracture. We included one trial reporting results at times ranging from two to 47 months for 81 people who had had an elbow fracture that involved the head of the radius. The evidence from this trial is of very low quality. The trial found no important differences between early and delayed mobilisation in the numbers of participants with pain or limitations in their range of elbow motion. All participants were reported as being able to use their arms for full activities of daily living and none had changed their occupation or lifestyle. There was no mention of fracture complications. We concluded that there was a lack of reliable evidence to answer the question of whether early mobilisation improved function without increasing complications in adults with elbow fractures. |
We included 27 trials, involving 10,187 participants, testing urokinase, streptokinase, rt-PA, recombinant pro-urokinase or desmoteplase. Four trials used intra-arterial administration, while the rest used the intravenous route. Most data come from trials that started treatment up to six hours after stroke. About 44% of the trials (about 70% of the participants) were testing intravenous rt-PA. In earlier studies very few of the participants (0.5%) were aged over 80 years; in this update, 16% of participants are over 80 years of age due to the inclusion of IST-3 (53% of participants in this trial were aged over 80 years). Trials published more recently utilised computerised randomisation, so there are less likely to be baseline imbalances than in previous versions of the review. More than 50% of trials fulfilled criteria for high-grade concealment; there were few losses to follow-up for the main outcomes. Thrombolytic therapy, mostly administered up to six hours after ischaemic stroke, significantly reduced the proportion of participants who were dead or dependent (modified Rankin 3 to 6) at three to six months after stroke (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.78 to 0.93). Thrombolytic therapy increased the risk of symptomatic intracranial haemorrhage (OR 3.75, 95% CI 3.11 to 4.51), early death (OR 1.69, 95% CI 1.44 to 1.98; 13 trials, 7458 participants) and death by three to six months after stroke (OR 1.18, 95% CI 1.06 to 1.30). Early death after thrombolysis was mostly attributable to intracranial haemorrhage. Treatment within three hours of stroke was more effective in reducing death or dependency (OR 0.66, 95% CI 0.56 to 0.79) without any increase in death (OR 0.99, 95% CI 0.82 to 1.21; 11 trials, 2187 participants). There was heterogeneity between the trials. Contemporaneous antithrombotic drugs increased the risk of death. Trials testing rt-PA showed a significant reduction in death or dependency with treatment up to six hours (OR 0.84, 95% CI 0.77 to 0.93, P = 0.0006; 8 trials, 6729 participants) with significant heterogeneity; treatment within three hours was more beneficial (OR 0.65, 95% CI 0.54 to 0.80, P < 0.0001; 6 trials, 1779 participants) without heterogeneity. Participants aged over 80 years benefited equally to those aged under 80 years, particularly if treated within three hours of stroke. Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people. Those treated within the first three hours derive substantially more benefit than with later treatment. This overall benefit was apparent despite an increase in symptomatic intracranial haemorrhage, deaths at seven to 10 days, and deaths at final follow-up (except for trials testing rt-PA, which had no effect on death at final follow-up). Further trials are needed to identify the latest time window, whether people with mild stroke benefit from thrombolysis, to find ways of reducing symptomatic intracranial haemorrhage and deaths, and to identify the environment in which thrombolysis may best be given in routine practice. | We identified 27 trials with a total of 10,187 participants in searches conducted up to November 2013. Most data come from trials testing one drug (recombinant tissue Plasminogen Activator, rt-PA) given into a vein up to six hours after acute ischaemic stroke, but several other drugs were also tested and at different times to treatment after stroke and given into an artery in the brain rather than into a vein in the arm. All trials compared a clot-dissolving drug with a placebo (control) group. Most trials included participants with moderate to severe stroke. All trials took place in hospitals that were used to treating people with stroke. Differences between trials mean that not all trials contribute information to all outcomes, but we have used all available data. Most trials included participants after a computed tomography (CT) brain scan had excluded a brain haemorrhage as the cause of symptoms (a few trials used magnetic resonance brain scanning instead). There is general agreement between the earlier trials and the one recent trial added in this update (IST-3) for all main outcomes, and between the 12 trials that tested rt-PA and the 15 trials that tested other clot-dissolving drugs. The main difference between IST-3 and earlier trials was that IST-3 had many participants above 80 years. Clot-dissolving treatment can reduce the risk of long-term dependency on others for daily activities, in spite of there being an increased risk of bleeding in the brain which also increased the risk of early death. Once the early bleeding risk had passed, at three or six months after stroke, people given clot-dissolving drugs were more likely to have recovered from their stroke and to be independent, especially if they had been treated within the first three hours after stroke. Older people benefited as much as younger people. Giving aspirin at the same time as clot-busting drugs increased the risk of bleeding and should be avoided. Further analyses of individual patient data factors such as findings on brain scanning before treatment, and of different ways of giving the treatment, may give more information than the summary data that we used here. Meantime, people who think that they are experiencing a stroke should get to hospital quickly, be assessed by a stroke doctor, have a brain scan and receive clot-dissolving treatment as fast as possible. They should not hesitate by thinking that they will be 'too old' for treatment. The treatment is very effective if started within three hours of stroke and definitely improves outcome if given up to 4.5 hours after stroke, but later than that the effects are less clear and are still being tested in trials. More information is needed from trials in people with mild stroke to see if the benefit of clot-dissolving drugs outweighs the risk of haemorrhage. The evidence comes mostly from well-conducted randomised trials run by stroke experts. Some trials (8/27) were run by companies that make the clot-dissolving drugs, but most trials (19/27, including most participants) were funded by Government or charity sources independently of drug companies. These results apply to a wide range of people with a wide range of severities of stroke and other medical conditions. |
We only found studies (47 studies, 3581 participants) for 18 of the 29 eligible TCHMs as defined by our inclusion criteria. All were superiority trials conducted in China between 1997 and 2013, with most employing a two-arm parallel design with sample sizes ranging from 26 to 240 and a median treatment duration of 12 weeks (range: 2 to 24 weeks). We found that reporting and trial methodology were generally poor; in particular, there was a lack of information on randomisation, an absence of blinding of participants and outcome assessors and incomplete reporting of adverse events (AEs). None of the 30 trials published from 2007 onwards adopted the CONSORT recommendations for reporting RCTs of herbal interventions. We found seven TCHMs which each had potentially large benefits in studies estimating the TCHM versus 'no treatment' effect and in studies estimating the TCHM versus the WM effect. Two TCHMs (NaoXinTong and TongXinLuo) were common to both groups. Three of these TCHMs – Nao XinTong, NaoMaiTai and TongXinLuo – had the strongest evidence to justify further research. Two TCHMs (NaoMaiTai and TongXinLuo) had a 5% or more increased risk of AEs compared to the 'no Treatment' control, but the quality of this evidence was poor. We found moderate- to very low-quality evidence of benefit and harm of TCHMs for VaD. Methodological inadequacies need to be addressed by better conducted and reported trials. We identified NaoMaiTai, NaoXinTong and TongXinLuo as warranting special research priority. | We included 47 trials with 3581 participants of 18 TCHMs in this review. All were conducted in mainland China between 1997 and 2013 with participant numbers ranging from 26 to 240 and an average study duration of 12 weeks. There were significant problems with the methods in many of the trials, particularly with how participants were allocated to treatments, how outcomes were measured and how thoroughly harmful effects were monitored. For these and other reasons, we rated the overall quality of the evidence as variable, ranging from moderate to very low. This means that we are uncertain, and often very uncertain, about the accuracy of the results. Despite these reservations, we found seven TCHMs which each had potentially large benefits in studies comparing TCHMs to no treatment or Western Medicine. Three of these – Nao XinTong, NaoMaiTai and TongXinLuo – had the strongest evidence to justify further research. We found that the risk of harmful effects was at least 5% higher than the risk for participants in the control group for NaoMaiTai and TongXinLuo, but the quality of this evidence was poor. We think further research of some TCHMs for vascular dementia is justified, but it is important that the quality of trial conduct and reporting be improved by adhering to published best-practice standards. |
In this review update, an additional three studies and 220 participants were added. A total of seven RCTs (two in adults, four in children, one in both children and adults) with 837 participants (aged from one to 63 years) with asthma from ethnic minority groups were eligible for inclusion in this review. The methodological quality of studies ranged from very low to low. For our primary outcome (asthma exacerbations during follow-up), the quality of evidence was low for all outcomes. In adults, use of a culture-specific programme, compared to generic programmes or usual care did not significantly reduce the number of participants from two studies with 294 participants for: exacerbations with one or more exacerbations during follow-up (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.50 to 1.26), hospitalisations over 12 months (OR 0.83, 95% CI 0.31 to 2.22) and exacerbations requiring oral corticosteroids (OR 0.97, 95% CI 0.55 to 1.73). However, use of a culture-specific programme, improved asthma quality of life scores in 280 adults from two studies (mean difference (MD) 0.26, 95% CI 0.17 to 0.36) (although the MD was less then the minimal important difference for the score). In children, use of a culture-specific programme was superior to generic programmes or usual care in reducing severe asthma exacerbations requiring hospitalisation in two studies with 305 children (rate ratio 0.48, 95% CI 0.24 to 0.95), asthma control in one study with 62 children and QoL in three studies with 213 children, but not for the number of exacerbations during follow-up (OR 1.55, 95% CI 0.66 to 3.66) or the number of exacerbations (MD 0.18, 95% CI -0.25 to 0.62) among 100 children from two studies. The available evidence showed that culture-specific education programmes for adults and children from minority groups are likely effective in improving asthma-related outcomes. This review was limited by few studies and evidence of very low to low quality. Not all asthma-related outcomes improved with culture-specific programs for both adults and children. Nevertheless, while modified culture-specific education programs are usually more time intensive, the findings of this review suggest using culture-specific asthma education programmes for children and adults from minority groups. However, more robust RCTs are needed to further strengthen the quality of evidence and determine the cost-effectiveness of culture-specific programs. | Seven studies with 837 participants, aged from one to 63 years old were included in this review update. This review was limited by few studies and the quality of evidence was very low to low. In adults, we found that culture-specific programmes did not improve any of our primary outcomes, but were better in improving quality of life (although the mean difference was less that the minimum important difference for the score) (secondary outcome). In children however, when data were combined from studies, culture-specific programmes reduced severe exacerbations requiring hospitalisation (primary outcome), while single studies showed improved asthma control, asthma knowledge and adherence outcomes for our secondary outcomes. The available evidence showed that culture-specific education programmes for adults and children from minority groups are likely effective in improving asthma-related outcomes. Although more robust evidence is required, asthma education programmes should be as culturally specific as possible in the context of chronic disease management and the complexity of health outcomes and culture, In the absence of any economic data, cost-effectiveness studies are also required The quality of the evidence was very low to low for all outcomes. |
Nine trials with 882 participants were included in the review. In five trials the outcome assessors were blind to the participants' intervention condition and in the remainder of trials it was unclear. In the majority of trials, participants were either not blind to their intervention condition, or it was unclear whether they were or not. Allocation concealment was also unclear in the majority of trials. Although all trials treated participants in an outpatient setting, the designs implemented in trials was diverse, which limits the generalisability of the results. Three trials indicated participants treated with antidepressant medication had lower relapse-recurrence rates (40.9%) compared to those treated with placebo (66.6%) during a relapse prevention phase (odds ratio (OR) 0.34; 95% confidence interval (CI) 0.18 to 0.64, P = 0.02). One trial that compared a combination of psychological therapy and medication to medication alone favoured a combination approach over medication alone, however this result did not reach statistical significance (OR 0.26; 95% CI 0.06 to 1.15). The majority of trials that involved antidepressant medication reported adverse events including suicide-related behaviours. However, there were not enough data to show which treatment approach results in the most favourable adverse event profile. Currently, there is little evidence to conclude which type of treatment approach is most effective in preventing relapse or recurrence of depressive episodes in children and adolescents. Limited trials found that antidepressant medication reduces the chance of relapse-recurrence in the future, however, there is considerable diversity in the design of trials, making it difficult to compare outcomes across studies. Some of the research involving psychological therapies is encouraging, however at present more trials with larger sample sizes need to be conducted in order to explore this treatment approach further. | This review aimed to determine the efficacy of early interventions, including psychological, social and pharmacological interventions to prevent relapse or recurrence of depressive disorders in children and adolescents.The review included nine studies that assessed the efficacy of antidepressant medication and psychological therapies in reducing the risk of a future depressive episode in children and adolescents. Trials varied in their quality and methodological design, limiting conclusions that could be drawn from the result. Overall, the review found that antidepressant medication reduces the chance that children and adolescents will experience another episode of depression, compared with a pill placebo. Psychological therapies also look promising as a treatment to prevent future depressive episodes, however given the aforementioned issues concerning trial quality and design, along with the small number of trials included in the review, it is unclear how effective these therapies are at present. |
We excluded nine studies because they were non-randomised trials or were withdrawn before enrolment. We included one study, which was conducted in two phases. During the first phase of the study, 77 children with ASD were randomly assigned to receive seven days of glutathione lotion or placebo lotion, followed by three days of oral dimercaptosuccinic acid (DMSA). Forty-nine children who were found to be high excreters of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off, with the cycle repeated up to six times. The second phase thus assessed the effectiveness of multiple doses of oral DMSA compared with placebo in children who were high excreters of heavy metals and who received a three-day course of oral DMSA. Overall, no evidence suggests that multiple rounds of oral DMSA had an effect on ASD symptoms. This review included data from only one study, which had methodological limitations. As such, no clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD. Given prior reports of serious adverse events, such as hypocalcaemia, renal impairment and reported death, the risks of using chelation for ASD currently outweigh proven benefits. Before further trials are conducted, evidence that supports a causal link between heavy metals and autism and methods that ensure the safety of participants are needed. | We searched multiple databases to find studies that examined pharmaceutical chelating agents as treatment for ASD symptoms. We found only one randomised controlled trial that evaluated oral dimercaptosuccinic acid (DMSA) for ASD, but this trial did not use ideal methods for answering our question. The evidence is current to November 2014. The trial that we found was conducted in two phases. During the first phase, 77 children with ASD were assigned randomly to receive seven days of glutathione lotion or placebo lotion, followed by three days of oral DMSA. Forty-nine children who excreted high levels of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off, with the cycle repeated up to six times. Results from the included study show that multiple rounds of oral DMSA did not have an effect on any of the ASD symptoms measured in children found to be high excreters who had already received three doses of a pharmaceutical chelating agent. Currently no clinical trial evidence suggests that pharmaceutical chelation is an effective intervention for ASD. Given prior reports of serious adverse events, such as changes to calcium levels in blood, kidney impairment and reported death, risks of using pharmaceutical chelating agents for ASD currently outweigh proven benefits. The quality of the evidence is poor, with only one study, which had methodological shortcomings, included in this review. These factors, when combined, preclude confidence in the findings. However, before further trials are conducted, more evidence is needed to show that heavy metals cause or worsen the severity of autism, and the safety of pharmaceutical chelating agents for participants must be established. |
The electronic literature search identified 1 original study that met the eligibility criteria. One unpublished study was also identified through manual searches. Therefore two randomized controlled trials met the inclusion criteria: Tscheikuna 2002 (via electronic searches) and Ruiz 1994 (via manual searches). Tscheikuna 2002, a double-blind RCT performed in Thailand, evaluated the effectiveness of tranexamic acid (TXA, an antifibrinolytic agent) administered orally in 46 hospital in- and outpatients with haemoptysis of various etiologies. Ruiz 1994, a double-blind RCT performed in Peru, evaluated the effectiveness of intravenous TXA in 24 hospitalised patients presenting with haemoptysis secondary to tuberculosis. Pooled together, results demonstrated a significant reduction in bleeding time between patients receiving TXA and patients receiving placebo with a weighted mean difference (WMD) of -19.47 (95% CI -26.90 to -12.03 hours), but with high heterogeneity (I² = 52%). TXA did not affect remission of haemoptysis evaluated at seven days after the start of treatment. Adverse effects caused by the drug's mechanism of action were not reported. There was no significant difference in the incidence of mild side effects between active and placebo groups (OR 3.13, 95% CI 0.80 to 12.24). There is insufficient evidence to judge whether antifibrinolytics should be used to treat haemoptysis from any cause, though limited evidence suggests they may reduce the duration of bleeding. | We identified two trials up to the 19th September 2016. Both of them evaluated the use of tranexamic acid, one for haemoptysis caused by tuberculosis and the other for haemoptysis from a variety of causes. Tranexamic acid significantly reduced the bleeding time, but it did not make any difference to the number of patients who were still suffering from haemoptysis when it was evaluated at seven days after the start of treatment. Severe adverse effects were not reported and mild side effects were not different between patients receiving tranexamic acid and those not receiving tranexamic acid. There is too little evidence to judge whether any antifibrinolytics should be used to treat haemoptysis. |
We included two studies, both comparing the effects of adding aspirin to standard antipsychotic treatment with adding placebo to standard antipsychotic treatment. We were hoping to find high-quality data for seven main outcomes of importance: clinically important change in global state, mental state, cognitive functioning and quality of life, numbers leaving the study early, incidence of gastrointestinal adverse events and hospital admission. Clinically important change data were not reported. Global state data were reported by one study as 'unspecified problem necessitating change in dose or type of antipsychotics'; there was no clear difference between treatment groups for this outcome (RR 0.75, 95% CI 0.30 to 1.88; studies = 1; participants = 70; very low-quality evidence). Both trials measured mental state using the Positive and Negative Symptom Scale (PANSS), and mean total PANSS endpoint scores favoured the adjunct aspirin group in the medium term (MD –6.56, 95% CI –12.04 to –1.08; studies = 2; participants = 130; very low-quality evidence). Less than 10% of each group's participants left the studies early (for any reason) and by around three months there was no clear difference between numbers leaving early from the aspirin group compared to numbers leaving early from the placebo group suggesting aspirin is acceptable (RR 1.12, 95% CI 0.40 to 3.14; studies = 2; participants = 130; very low-quality evidence). There was some gastric upset in both groups but rates were not clearly different between the treatment groups (RR 1.03, 95% CI 0.55 to 1.94; studies = 1; participants = 70; very low-quality evidence). We are unclear if 'change in hospital status' is an unfavourable outcome or not as one study reported equivocal data (RR 0.56, 95% CI 0.05 to 5.90; studies = 1; participants = 70; very low-quality evidence). It should be noted that all the above results were based on data of very low-quality and were difficult to interpret for clinicians or patients, and that the two studies, completed in the last decade, failed to report any usable outcomes on cognitive functioning or quality of life. We highlighted the evidence that some pioneering researchers feel this question is important enough to merit testing in randomised trials. However, we also highlighted that the evidence produced from these trials was weak and inconclusive. It was impossible to draw clear conclusions on the therapeutic value of aspirin for schizophrenia from these short, small and limited trials. | After searching Cochrane Schizophrenia's database in March 2018 and assessing the search results, we included one randomised controlled trial (clinical studies where people are randomly put into one of two or more treatment groups) from the Netherlands (70 participants) and one from Iran (60 participants). Both trials used aspirin as an add-on treatment to standard antipsychotic medication and compared it with placebo (a dummy treatment), also as an add-on to standard treatment. Participants receiving aspirin had slightly better results for their mental state, which was measured with the Positive and Negative Symptom Scale (PANSS). For side effects related to stomach problems, there seemed to be no clear difference between the groups. The same applied to changes in hospital status and leaving the study early. However, all these results were based on analyses of very poor data and graded as very low-quality evidence. No trial gave usable information on cognitive functioning or quality of life. This review was based on results from only two small trials, which made it impossible to say whether aspirin would be a good treatment option for people with schizophrenia. More information from the trials that are underway could strengthen the results of this analysis. |
We included six trials with 520 patients comparing pre-operative biliary drainage (265 patients) versus no pre-operative biliary drainage (255 patients). Four trials used percutaneous transhepatic biliary drainage and two trials used endoscopic sphincterotomy and stenting as the method of pre-operative biliary drainage. The risk of bias was high in all trials. The proportion of patients with malignant obstruction varied between 60% and 100%. There was no significant difference in mortality (40/265, weighted proportion 14.9%) in the pre-operative biliary drainage group versus the direct surgery group (34/255, 13.3%) (RR 1.12; 95% CI 0.73 to 1.71; P = 0.60). The overall serious morbidity was higher in the pre-operative biliary drainage group (60 per 100 patients in the pre-operative biliary drainage group versus 26 per 100 patients in the direct surgery group) (RaR 1.66; 95% CI 1.28 to 2.16; P = 0.0002). The proportion of patients who developed serious morbidity was significantly higher in the pre-operative biliary drainage group (75/102, 73.5%) in the pre-operative biliary drainage group versus the direct surgery group (37/94, 37.4%) (P < 0.001). Quality of life was not reported in any of the trials. There was no significant difference in the length of hospital stay (2 trials, 271 patients; MD 4.87 days; 95% CI -1.28 to 11.02; P = 0.12) between the two groups. Trial sequential analysis showed that for mortality only a small proportion of the required information size had been obtained. There seemed to be no significant differences in the subgroup of trials assessing percutaneous compared to endoscopic drainage. There is currently not sufficient evidence to support or refute routine pre-operative biliary drainage for patients with obstructive jaundice. Pre-operative biliary drainage may increase the rate of serious adverse events. So, the safety of routine pre-operative biliary drainage has not been established. Pre-operative biliary drainage should not be used in patients undergoing surgery for obstructive jaundice outside randomised clinical trials. | We included six trials involving 510 patients for this review. The number of patients included in the trials varied from 40 to 202. All trials had a high risk of bias, that is, the trials may overestimate benefits and underestimate harms. There was no significant difference in risk of death between the two groups. The rate of serious complications was higher in the patients who underwent biliary drainage prior to operation compared with those who underwent surgery directly. The quality of life was not reported in any trial. There was no significant difference in the length of hospital stay between the two groups. The costs were not reported in any of the trials. Based on the currently available best evidence, there is no justification for the use of routine drainage of bile before a major operation in patients with obstruction to the flow of bile. Routine biliary drainage should not be funded and may result in litigations. Furthermore, well designed trials with low risk of systematic errors and low risk of random errors (low risk of play of chance) may be necessary. |
One of 17 studies retrieved for full-text assessment for eligibility was included in the final analysis. This study included a total of 186 participants and investigated the effect of LMWH to prevent CVC-related thrombosis compared to standard care. The risk of bias of the study was assessed to be low, except for the unclear risk of selection bias (allocation concealment not reported) and detection bias since it was an open-label study. Nonetheless, outcome adjudication was blinded. However, overall the quality of the evidence was low due to the fact that the study was underpowered. The CIs for the risk of CVC-related thrombosis (symptomatic and asymptomatic events) were compatible with benefits of either LMWH (reviparin) or the control (RR for symptomatic thrombosis 1.03, 95% CI 0.21 to 4.93; RR for asymptomatic thrombosis 1.17, 95% CI 0.45 to 3.08). Similarly, only one patient in the standard care group suffered a major bleeding event, while minor bleeding was found in 53.3% of patients in the reviparin arm and in 44.7% of patients in the standard care arm (major bleeding RR 0.34, 95% CI 0.01 to 8.26; minor bleeding RR 1.20, 95% CI 0.91 to 1.58). Lastly, there were two deaths within the study and neither were the result of a venous thrombotic event (VTE), occurring in the standard care arm. No additional adverse effects were reported. Other pre-specified outcomes for this review were not reported. A single study reported imprecise effects for the risk of CVC-related thrombosis in children on a CVC anticoagulant prophylaxis regimen. The quality of the evidence was low due to the fact that the included study was clearly underpowered, hampering any conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombi in children. Further prospective randomised studies are highly encouraged. | Therefore, we looked at all the research in children with central lines who received, or not, LMWH and only found one study with a total of 186 participants. This study did not have enough participants to show if this medication protects children with central lines from getting blood clots. The study also did not show that children on LMWH, at the doses given, experience too much bleeding because of its use. The included study did not report any additional adverse events. There were two deaths within the study in the standard care arm, and neither were due to a blood clot. Future studies looking at the role of this medication (LMWH) and if it protects children with central venous lines from getting blood clots are needed. |
This review included 10 studies with a total number of 686 participants featuring in 20 different outcomes of interest. Overall, there was significant clinical improvement in clinical global state at medium term amongst people receiving trifluoperazine (3 RCTs, n = 417, RR 4.61, CI 1.54 to 13.84, low quality evidence) and significantly fewer people receiving trifluoperazine left the studies early due to relapse or worsening at medium term (2 RCTs, n = 381, RR 0.34, CI 0.23 to 0.49, low quality evidence). However, results were equivocal for leaving the study early at medium term for any reason (2 RCTs, n = 391, RR 0.80, CI 0.17 to 3.81, very low quality evidence) and due to severe adverse effects (2 RCTs, n = 391, RR 1.54, CI 0.56 to 4.24, very low quality evidence). Equivocal data were also found for intensified symptoms at medium term (2 RCTs, n = 80, RR 1.05, CI 0.54 to 2.05, very low quality evidence) and rates of agitation or distress again at medium term (1 RCT, n = 52, RR 2.00, CI 0.19 to 20.72, very low quality evidence). Comparison between low and high-dose trifluoperazine with placebo from a single study provided equivocal evidence of effects. For economic outcomes, we valued outcomes in GBP terms and presented them in additional tables; there was an estimated saving of £3488.3 in favour of trifluoperazine. However, numerous assumptions were made and these savings need to be interpreted in light of those assumptions. Our results agree with existing evidence that compared to placebo, trifluoperazine is an effective antipsychotic for people with schizophrenia. Furthermore, our review provides supportive evidence that trifluoperazine increases the risk of extrapyramidal adverse effects. Although the effect sizes against placebo are similar to those observed with other agents, they are based on data from many small, pre-CONSORT trials with generally either a low or very low GRADE evidence that has limited implication for clinical practice. Large, independent trials are needed that adhere to the CONSORT statement to compare trifluoperazine with placebo used in the treatment of schizophrenia and schizophrenia-like illnesses. | This review is based on a search for trials carried out in July 2012, and includes 10 studies with 686 participants. The aim was to determine the effects of trifluoperazine for schizophrenia when compared with placebo (a ‘dummy’ treatment). As expected, people given trifluoperazine showed a significant improvement compared to placebo in both the short and medium term, reinforcing the use of this well-established typical antipsychotic for people with schizophrenia. However, trifluoperazine can cause side effects such as confusion, agitation, having a dry mouth and blurred vision, but causes less sedation and dizzy spells, so is generally well tolerated by people with schizophrenia. The authors of the review conclude that trifluoperazine has similar effectiveness to other common antipsychotic drugs, although it may cause more side effects. Evidence used in the review was also graded as low or very low quality. In the light of this, use of other antipsychotic drugs should be considered before starting on trifluoperazine. Most of the included studies were conducted roughly 40 years ago so new, large, comprehensive and independent research trials are needed. This plain language summary has been written by a consumer Ben Gray from RETHINK. |
We included 8 trials involving 263 people with PD in the review. Risk of bias was unclear or high for all but one of the included studies. Study sample sizes were small, and there was a large amount of heterogeneity between trials with regard to study design and the outcome measures used. As a result, we graded the quality of the evidence as low or very low. Most of the studies intended to improve motor function using commercially available devices, which were compared with physiotherapy. The interventions lasted for between 4 and 12 weeks. In comparison to physiotherapy, VR may lead to a moderate improvement in step and stride length (standardised mean difference (SMD) 0.69, 95% confidence interval (CI) 0.30 to 1.08; 3 studies; 106 participants; low-quality evidence). VR and physiotherapy interventions may have similar effects on gait (SMD 0.20, 95% CI -0.14 to 0.55; 4 studies; 129 participants; low-quality evidence), balance (SMD 0.34, 95% CI -0.04 to 0.71; 5 studies; 155 participants; low-quality evidence), and quality of life (mean difference 3.73 units, 95% CI -2.16 to 9.61; 4 studies; 106 participants). VR interventions did not lead to any reported adverse events, and exercise adherence did not differ between VR and other intervention arms. The evidence available comparing VR exercise with a passive control was more limited. The evidence for the main outcomes of interest was of very low quality due to the very small sample sizes of the two studies available for this comparison. We found low-quality evidence of a positive effect of short-term VR exercise on step and stride length. VR and physiotherapy may have similar effects on gait, balance, and quality of life. The evidence available comparing VR with passive control interventions was more limited. Additional high-quality, large-scale studies are needed to confirm these findings. | We conducted the literature search up until 26 November 2016. We identified 8 studies involving a total of 263 participants with PD. All trials aimed to improve either gait or balance function. Most of the studies compared VR with physiotherapy. VR interventions may lead to greater improvements in step and stride length compared with physiotherapy interventions. We found limited evidence that improvements in gait, balance, and quality of life were similar to those found in active control interventions. No adverse events were reported. Fewer studies compared VR with passive control interventions, and evidence was insufficient to determine how VR compares with no active intervention. At present, only a few studies have been done, making generalisation of the findings difficult. Further study is needed to confirm and expand the evidence base for VR in PD. In general, the quality of the evidence was low or very low. This was the result of small sample sizes and a large amount of heterogeneity between trials with regard to study design and outcome measures used. |
Thirteen studies were identified as possibly eligible for inclusion. The majority of studies were excluded as they did not separate data for early and late onset infection. Two studies are still awaiting assessment. Only one small study, in 24 neonates, was included in this review. It compared beta-lactam therapy with a combination of beta lactam plus aminoglycoside. The study did not meet our prespecified criteria for good methodological quality. In babies with suspected infection there was no significant difference in mortality (RR 0.17, 95% CI 0.01 to 3.23) or treatment failure (RR 0.17, 95% CI 0.01 to 3.23). Antibiotic resistance was assessed and there were no cases in either group. There is inadequate evidence from randomised trials in favour of any particular antibiotic regimen for the treatment of suspected late onset neonatal sepsis. The available evidence is not of high quality. Although suspected sepsis and antibiotic use is common, quality research is required to specifically address both narrow and broad spectrum antibiotic use for late onset neonatal sepsis. Future research also needs to assess cost effectiveness and the impact of antibiotics in different settings such as developed or developing countries and lower gestational age groups. | This Cochrane review examined which antibiotics are best for treating late onset neonatal sepsis, in terms of effectiveness and side effects. The authors searched the medical literature and found only one study that met all the criteria the authors were looking for. This study, from 1988, enrolled 28 newborn infants. Some of the newborns received a beta lactam antibiotic by itself while others got the beta lactam plus another antibiotic, an aminoglycoside. There were no significant differences between the two kinds of antibiotic treatment in this study. The Cochrane review authors concluded that there is not enough research to recommend one kind of antibiotic treatment over another for late onset neonatal sepsis. |
We included 32 trials (1836 participants). No trial compared a combination of manual therapy and exercise versus placebo or no intervention. Seven trials compared a combination of manual therapy and exercise versus other interventions but were clinically heterogeneous, so opportunities for meta-analysis were limited. The overall impression gained from these trials is that the few outcome differences between interventions that were clinically important were detected only up to seven weeks. Evidence of moderate quality shows that a combination of manual therapy and exercise for six weeks probably results in less improvement at seven weeks but a similar number of adverse events compared with glucocorticoid injection. The mean change in pain with glucocorticoid injection was 58 points on a 100-point scale, and 32 points with manual therapy and exercise (mean difference (MD) 26 points, 95% confidence interval (CI) 15 points to 37 points; one RCT, 107 participants), for an absolute difference of 26% (15% to 37%). Mean change in function with glucocorticoid injection was 39 points on a 100-point scale, and 14 points with manual therapy and exercise (MD 25 points, 95% CI 35 points to 15 points; one RCT, 107 participants), for an absolute difference of 25% (15% to 35%). Forty-six per cent (26/56) of participants reported treatment success with manual therapy and exercise compared with 77% (40/52) of participants receiving glucocorticoid injection (risk ratio (RR) 0.6, 95% CI 0.44 to 0.83; one RCT, 108 participants), with an absolute risk difference of 30% (13% to 48%). The number reporting adverse events did not differ between groups: 56% (32/57) reported events with manual therapy and exercise, and 53% (30/57) with glucocorticoid injection (RR 1.07, 95% CI 0.76 to 1.49; one RCT, 114 participants), with an absolute risk difference of 4% (-15% to 22%). Group differences in improvement in overall pain and function at six months and 12 months were not clinically important. We are uncertain of the effect of other combinations of manual therapy and exercise, as most evidence is of low quality. Meta-analysis of two trials (86 participants) suggested no clinically important differences between a combination of manual therapy, exercise, and electrotherapy for four weeks and placebo injection compared with glucocorticoid injection alone or placebo injection alone in terms of overall pain, function, active range of motion and quality of life at six weeks, six months and 12 months (though the 95% CI suggested function may be better with glucocorticoid injection at six weeks). The same two trials found that adding a combination of manual therapy, exercise and electrotherapy for four weeks to glucocorticoid injection did not confer clinically important benefits over glucocorticoid injection alone at each time point. Based on one high quality trial (148 participants), following arthrographic joint distension with glucocorticoid and saline, a combination of manual therapy and supervised exercise for six weeks conferred similar effects to those of sham ultrasound in terms of overall pain, function and quality of life at six weeks and at six months, but provided greater patient-reported treatment success and active shoulder abduction at six weeks. One trial (119 participants) found that a combination of manual therapy, exercise, electrotherapy and oral non-steroidal anti-inflammatory drug (NSAID) for three weeks did not confer clinically important benefits over oral NSAID alone in terms of function and patient-reported treatment success at three weeks. On the basis of 25 clinically heterogeneous trials, we are uncertain of the effect of manual therapy or exercise when not delivered together, or one type of manual therapy or exercise versus another, as most reported differences between groups were not clinically or statistically significant, and the evidence is mostly of low quality. The best available data show that a combination of manual therapy and exercise may not be as effective as glucocorticoid injection in the short-term. It is unclear whether a combination of manual therapy, exercise and electrotherapy is an effective adjunct to glucocorticoid injection or oral NSAID. Following arthrographic joint distension with glucocorticoid and saline, manual therapy and exercise may confer effects similar to those of sham ultrasound in terms of overall pain, function and quality of life, but may provide greater patient-reported treatment success and active range of motion. High-quality RCTs are needed to establish the benefits and harms of manual therapy and exercise interventions that reflect actual practice, compared with placebo, no intervention and active interventions with evidence of benefit (e.g. glucocorticoid injection). | This summary of an updated Cochrane review presents what we know from research about the benefits and harms of manual therapy and exercise in people with frozen shoulder. After searching for all relevant studies published up to May 2013, we included 32 trials (1836 participants). Among the included participants, 54% were women, average age was 55 years and average duration of the condition was six months. The average duration of manual therapy and exercise interventions was four weeks. —manual therapy and exercise compared with glucocorticoid (a steroid that reduces inflammation) injection into the shoulder Pain (higher scores mean worse pain) People who had manual therapy and exercise for six weeks did not improve as much as people who had glucocorticoid injection—improvement in pain was 26 points less (ranging from 15 to 37 points less) at seven weeks (26% absolute less improvement). • People who had manual therapy and exercise rated their change in pain score as 32 points on a scale of 0 to 100 points. • People who had glucocorticoid injection rated their change in pain score as 58 points on a scale of 0 to 100 points. Function (lower scores mean better function) People who had manual therapy and exercise for six weeks did not improve as much as people who had glucocorticoid injection—improvement in function was 25 points less (ranging from 15 to 35 points less) at seven weeks (25% absolute less improvement). • People who had manual therapy and exercise rated their change in function as 14 points on a scale of 0 to 100 points. • People who had glucocorticoid injection rated their change in function as 39 points on a scale of 0 to 100 points. Treatment success 31 fewer people out of 100 rated their treatment as successful with manual therapy and exercise for six weeks compared with glucocorticoid injection—31% absolute less improvement (ranging from 13% to 48% less improvement). • 46 out of 100 people reported treatment success with manual therapy and exercise. • 77 out of 100 people reported treatment success with glucocorticoid injection. Side effects Out of 100 people, three had minor side effects such as temporary pain after treatment with manual therapy and exercise for six weeks compared with glucocorticoid injection. • 56 out of 100 people reported side effects with manual therapy and exercise. • 53 out of 100 people reported side effects with glucocorticoid injection. Evidence of moderate quality shows that the combination of manual therapy and exercise probably improves pain and function less than glucocorticoid injection up to seven weeks, and probably does not result in more adverse events. Further research may change the estimate. Low-quality evidence suggests that (1) the combination of manual therapy, exercise and electrotherapy (such as therapeutic ultrasound) may not improve pain or function more than glucocorticoid injection or placebo injection into the shoulder, (2) the combination of manual therapy, exercise, electrotherapy and glucocorticoid injection may not improve pain or function more than glucocorticoid injection alone and (3) the combination of manual therapy, exercise, electrotherapy and oral non-steroidal anti-inflammatory drug (NSAID) may not improve function more than oral NSAID alone. Further research is likely to change the estimate. High-quality evidence shows that following arthrographic joint distension, the combination of manual therapy and exercise does not improve pain or function more than sham ultrasound, but may provide greater patient-reported treatment success and active range of motion. Further research is very unlikely to change our confidence in the estimate of effect. No trial compared the combination of manual therapy and exercise versus placebo or no intervention. |
We included two trials that compared surgical with non-surgical treatment for patients with thoracolumbar burst fractures without neurological deficit. These recruited a total of 87 participants and reported outcomes for 79 participants at follow-up of two years or more. Both trials were judged at unclear risk of selection bias and at high risk of performance and detection biases, resulting from lack of blinding. The two trials reported contrasting results for pain and function-related outcomes at final follow-up, and numbers returning to work. One trial found less pain (mean difference (MD) -15.09 mm, 95% CI -27.81 to -2.37; 100 mm visual analogue scale), and better function based on the Roland and Morris disability questionnaire results (MD -5.87, 95% CI -10.10 to -1.64; 24 points = maximum disability) in the surgical group. Based on the same outcome measures, the other trial found the surgical group had more pain (MD 13.60 mm, 95% CI -0.31 to 27.51) and worse function (MD 4.31, 95% CI 0.54 to 8.08). Neither trial reported a statistically significant difference in return to work. There were greater numbers of participants with complications in the surgical group of both trials (21/41 versus 6/38; RR 2.85, 95% CI 0.83 to 9.75; 2 trials), and only participants of this group had subsequent surgery, involving implant removal either for complications or as a matter of course. One trial reported that surgery was over four times more costly than non-surgical treatment. The contradictory evidence provided by two small and potentially biased randomised controlled trials is insufficient to conclude whether surgical or non-surgical treatment yields superior pain and functional outcomes for people with thoracolumbar burst fractures without neurological deficit. It is likely, however, that surgery is associated with more early complications and the need for subsequent surgery, as well as greater initial healthcare costs. | We included data from two trials, which included 87 participants. The trials compared surgical with non-surgical treatment for these fractures in the thoracolumbar region of the spine. Both trials had limitations in their methods that could reduce the reliability of their results. They reported contrasting results for patient pain and function at a minimum of two years after treatment. One study found patients had less pain and better function after surgery compared with patients who did not have surgery. The other trial found the opposite. Both trials found there were more early complications in the surgical group and only participants of this group had subsequent additional surgery. This involved the removal of the implant either to resolve a complication or routinely. One trial reported that surgery was over four times more costly than non-surgical treatment. Our review concluded that the weak evidence from these two trials was insufficient to say whether surgery or non-surgical treatment was better for these fractures. However, surgery is likely to be associated with more early complications and the need for subsequent surgery, as well as greater initial healthcare costs. |
We included eight studies with 957 participants. The mean age of participants in the studies ranged from 78 to 88 years and in seven studies the mean MMSE score was 12 or lower. Seven studies were randomised controlled trials (three individually randomised, parallel group studies, one individually randomised cross-over study and three cluster-randomised trials) and one study was a non-randomised clinical trial. Five studies included a control group receiving usual care, two studies an active control intervention (activities which were not personally tailored) and one study included both an active control and usual care. Personally tailored activities were mainly delivered directly to the participants; in one study the nursing staff were trained to deliver the activities. The selection of activities was based on different theoretical models but the activities did not vary substantially. We found low-quality evidence indicating that personally tailored activities may slightly improve challenging behaviour (standardised mean difference (SMD) −0.21, 95% confidence interval (CI) −0.49 to 0.08; I² = 50%; 6 studies; 439 participants). We also found low-quality evidence from one study that was not included in the meta-analysis, indicating that personally tailored activities may make little or no difference to general restlessness, aggression, uncooperative behaviour, very negative and negative verbal behaviour (180 participants). There was very little evidence related to our other primary outcome of quality of life, which was assessed in only one study. From this study, we found that quality of life rated by proxies was slightly worse in the group receiving personally tailored activities (moderate-quality evidence, mean difference (MD) −1.93, 95% CI −3.63 to −0.23; 139 participants). Self-rated quality of life was only available for a small number of participants, and there was little or no difference between personally tailored activities and usual care on this outcome (low-quality evidence, MD 0.26, 95% CI −3.04 to 3.56; 42 participants). We found low-quality evidence that personally tailored activities may make little or no difference to negative affect (SMD −0.02, 95% CI −0.19 to 0.14; I² = 0%; 6 studies; 589 participants). We found very low quality evidence and are therefore very uncertain whether personally tailored activities have any effect on positive affect (SMD 0.88, 95% CI 0.43 to 1.32; I² = 80%; 6 studies; 498 participants); or mood (SMD −0.02, 95% CI −0.27 to 0.23; I² = 0%; 3 studies; 247 participants). We were not able to undertake a meta-analysis for engagement and the sleep-related outcomes. We found very low quality evidence and are therefore very uncertain whether personally tailored activities improve engagement or sleep-related outcomes (176 and 139 participants, respectively). Two studies that investigated the duration of the effects of personally tailored activities indicated that the intervention effects persisted only during the delivery of the activities. Two studies reported information about adverse effects and no adverse effects were observed. Offering personally tailored activities to people with dementia in long-term care may slightly improve challenging behaviour. Evidence from one study suggested that it was probably associated with a slight reduction in the quality of life rated by proxies, but may have little or no effect on self-rated quality of life. We acknowledge concerns about the validity of proxy ratings of quality of life in severe dementia. Personally tailored activities may have little or no effect on negative affect and we are uncertain whether they improve positive affect or mood. There was no evidence that interventions were more likely to be effective if based on one specific theoretical model rather than another. Our findings leave us unable to make recommendations about specific activities or the frequency and duration of delivery. Further research should focus on methods for selecting appropriate and meaningful activities for people in different stages of dementia. | Offering personally tailored activities to people with dementia living in care homes may slightly improve challenging behaviour when compared with usual care, although we did not find evidence that it was any better than offering activities which were not personally tailored. In one study, staff members reported that people in the group receiving personally tailored activities had a slightly worse quality of life than the control group. Personally tailored activities may have little or no effect on the negative emotions expressed by the participants. Because the quality of some of the evidence was very low, we could not draw any conclusions about effects on the participants' positive emotions, mood, engagement (being involved in what is happening around them) or quality of sleep. Only two studies mentioned looking for harmful effects; none were reported. None of the studies measured effects on the amount of medication participants were given, or effects on carers. We concluded that offering activity sessions to people with moderate or severe dementia living in care homes may help to manage challenging behaviour. However, we did not find any evidence to support the idea that activities were more effective if they were tailored to people's individual interests. More research of better quality is needed before we can be certain about the effects of personally tailored activities. |
We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction. For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to ameliorate opioid withdrawal, without clinically significant adverse effects. The meta-analyses that were possible support a conclusion of no difference between buprenorphine and methadone in terms of average treatment duration (mean difference (MD) 1.30 days, 95% confidence interval (CI) −8.11 to 10.72; N = 82; studies = 2; low quality) or treatment completion rates (risk ratio (RR) 1.04, 95% CI 0.91 to 1.20; N = 457; studies = 5; moderate quality). Relative to clonidine or lofexidine, buprenorphine was associated with a lower average withdrawal score (indicating less severe withdrawal) during the treatment episode, with an effect size that is considered to be small to moderate (standardised mean difference (SMD) −0.43, 95% CI −0.58 to −0.28; N = 902; studies = 7; moderate quality). Patients receiving buprenorphine stayed in treatment for longer, with an effect size that is considered to be large (SMD 0.92, 95% CI 0.57 to 1.27; N = 558; studies = 5; moderate quality) and were more likely to complete withdrawal treatment (RR 1.59, 95% CI 1.23 to 2.06; N = 1264; studies = 12; moderate quality). At the same time there was no significant difference in the incidence of adverse effects, but dropout due to adverse effects may be more likely with clonidine (RR 0.20, 95% CI 0.04 to 1.15; N = 134; studies = 3; low quality). The difference in treatment completion rates translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 6), indicating that for every four people treated with buprenorphine, we can expect that one additional person will complete treatment than with clonidine or lofexidine. For studies comparing different rates of reduction of the buprenorphine dose, meta-analysis was possible only for treatment completion, with separate analyses for inpatient and outpatient settings. The results were diverse, and we assessed the quality of evidence as being very low. It remains very uncertain what effect the rate of dose taper has on treatment outcome. Buprenorphine is more effective than clonidine or lofexidine for managing opioid withdrawal in terms of severity of withdrawal, duration of withdrawal treatment, and the likelihood of treatment completion. Buprenorphine and methadone appear to be equally effective, but data are limited. It remains possible that the pattern of withdrawal experienced may differ and that withdrawal symptoms may resolve more quickly with buprenorphine. It is not possible to draw any conclusions from the available evidence on the relative effectiveness of different rates of tapering the buprenorphine dose. The divergent findings of studies included in this review suggest that there may be multiple factors affecting the response to the rate of dose taper. One such factor could be whether or not the initial treatment plan includes a transition to subsequent relapse prevention treatment with naltrexone. Indeed, the use of buprenorphine to support transition to naltrexone treatment is an aspect worthy of further research. Most participants in the studies included in this review were male. None of the studies reported outcomes on the basis of sex, preventing any exploration of differences related to this variable. Consideration of sex as a factor influencing response to withdrawal treatment would be relevant research for selecting the most appropriate type of intervention for each individual. | We identified 27 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups), involving 3048 opioid-dependent participants. For 21 studies the average age of participants was in the range 25 to 40 years − in one study the average age was 47 years, while in two studies involving adolescents, the average age of participants was in the range 17 to 20 years (3 studies did not report the average age of participants). In four studies, all or nearly all participants were male, while in three studies less than half the participants were male. In most studies males comprised between one half and three-quarters of participants, a balance that is typical of the population of people who are opioid dependent. Fourteen of the studies took place in the USA, while the remaining studies were in eight other countries. The studies compared buprenorphine with methadone (6 studies), clonidine or lofexidine (14 studies), or different rates of buprenorphine dose reduction (7 studies). Fourteen studies reported funding from sources other than industry; in seven studies funding or medications were provided by a pharmaceutical company. The funding source was unclear for seven studies. Compared to clonidine or lofexidine, people receiving buprenorphine for opioid withdrawal will have less severe signs and symptoms, be likely to stay in treatment longer, experience fewer side effects, and be more likely to complete the scheduled period of treatment. The effectiveness of buprenorphine is probably similar to tapered doses of methadone, but we are uncertain whether withdrawal symptoms resolve more quickly with buprenorphine. We are also uncertain whether rapid reduction in the dose of buprenorphine is more effective than slow reduction and whether this depends on the context of withdrawal. We assessed the quality of the evidence to be very low to moderate for the comparison of buprenorphine versus clonidine or lofexidine, low to moderate for the comparison of buprenorphine versus methadone, and very low to low for the comparison of different rates of dose reduction. Further evidence could change the findings, particularly for buprenorphine compared to methadone and for different rates of reduction of buprenorphine dose. |
We have included nine studies in this review. All were part of the original systematic review; no new trials meeting eligibility criteria were identified through our updated searches. The studies were conducted in eight different states of the USA, during the years 1967 to 1992. Nearly 1000 (946) juveniles or young adults of different races participated, almost all males. The average age of the participants in each study ranged from 15 to 17 years. Meta-analyses of seven studies show the intervention to be more harmful than doing nothing. The OR (fixed-effect) for effects on first post-treatment effect on officially measured criminal behavior indicated a negative program effect (OR 1.68, 95% confidence interval (CI) 1.20 to 2.36) and nearly identical regardless of the meta-analytic strategy (random-effects OR 1.72, 95% CI 1.13 to 2.62). Sensitivity analyses (random-effects) showed the findings were robust even when removing one study with an inadequate randomization strategy (OR 1.47, 95% CI 1.03 to 2.11), or when removing one study with high attrition (OR 1.96, 95% CI 1.25 to 3.08), or both (OR 1.68, 95% CI 1.10 to 2.58). We conclude that programs such as 'Scared Straight' increase delinquency relative to doing nothing at all to similar youths. Given these results, we cannot recommend this program as a crime prevention strategy. Agencies that permit such programs, therefore, must rigorously evaluate them, to ensure that they do not cause more harm than good to the very citizens they pledge to protect. | This review, which is an update of one published in 2002, includes nine studies that involved 946 teenagers, almost all males. The studies were conducted in different parts of the USA and involved young people of different races whose average age ranged from 15 to 17 years. Results indicate that not only do these programs fail to deter crime, but they actually lead to more offending behavior. The intervention increases the odds of offending by between 1.6 to 1 and 1.7 to 1. Government officials permitting this program need to adopt rigorous evaluation efforts to ensure that they are not causing more harm to the very citizens they pledge to protect. |
We were able to include two trials involving 321 people with severe mental illnesses. There was no significant difference in hospital admission (n=160, 1 RCT, RR 0.69 0.5 to 1.0), or number of psychiatric outpatient attendances between participants given advanced treatment directives or usual care. Similarly, no significant differences were found for compliance with treatment, self harm or number of arrests. Participants given advanced treatment directives needed less use of social workers time (n=160, 1 RCT, WMD -106.00 CI -156.2 to -55.8) than the usual care group, and violent acts were also lower in the advanced directives group (n=160, 1 RCT, RR 0.27 CI 0.1 to 0.9, NNT 8 CI 6 to 92). The number of people leaving the study early were not different between groups (n=321, 2 RCTs, RR 0.92 CI 0.6 to 1.6). The addition of 11 studies to awaiting classification section of the review may alter the conclusions of the review once assessed. There are too few data available to make definitive recommendations. More intensive forms of advance directive appear to show promise, but currently practice must be guided by evidence other than that derived from randomised trials. More trials are indicated to determine whether higher intensity interventions, such as joint crisis planning, have an effect on outcomes of clinical relevance. | This review looks at whether having an advance statement leads to less hospitalisation (either voluntary or involuntary), less contact with mental health services and whether there is an improvement in general functioning. Two studies were found, involving 321 people. Both took place in England. One trial involved the person concerned making a joint crisis plan in collaboration with the psychiatrist, care coordinator and project worker (high intensity), while the other required filling in a booklet called ‘preferences for care’ (low intensity). Both studies were compared to the usual care in the area concerned. Since the interventions were quite different, and not all outcomes were measured by both studies, it is quite difficult to compare the trials. Those who filled in the booklet showed no decrease in admission to hospital (voluntary or involuntary) or contact with out-patient services, when compared to usual care. The high intensity group showed no differences in voluntary admissions compared to those in usual care, but were less likely to be hospitalised involuntarily, or assessed under the Mental Health Act. They were also less likely to be violent. There was no difference in use of psychiatric out-patient services by those in the intervention groups. These are small studies and more research is needed, but it is suggested that using an advance treatment directive could be an alternative to community treatment orders. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org) |
Thirty-five trials (3573 women) with 15 comparisons were included. Women allocated calcium channel blockers were less likely to have persistent high blood pressure compared to those allocated hydralazine (six trials, 313 women; 8% versus 22%; risk ratio (RR) 0.37, 95% confidence interval (CI) 0.21 to 0.66). Ketanserin was associated with more persistent high blood pressure than hydralazine (three trials, 180 women; 27% versus 6%; RR 4.79, 95% CI 1.95 to 11.73), but fewer side-effects (three trials, 120 women; RR 0.32, 95% CI 0.19 to 0.53) and a lower risk of HELLP (haemolysis, elevated liver enzymes and lowered platelets) syndrome (one trial, 44 women; RR 0.20, 95% CI 0.05 to 0.81). Labetalol was associated with a lower risk of hypotension compared to diazoxide (one trial 90 women; RR 0.06, 95% CI 0.00 to 0.99) and a lower risk of caesarean section (RR 0.43, 95% CI 0.18 to 1.02), although both were borderline for statistical significance. Both nimodipine and magnesium sulphate were associated with a high incidence of persistent high blood pressure, but this risk was lower for nimodipine compared to magnesium sulphate (one trial, 1650 women; 47% versus 65%; RR 0.84, 95% CI 0.76 to 0.93). Nimodipine was associated with a lower risk of respiratory difficulties (RR 0.28, 95% CI 0.08 to 0.99), fewer side-effects (RR 0.68, 95% CI 0.55 to 0.85) and less postpartum haemorrhage (RR 0.41, 95% CI 0.18 to 0.92) than magnesium sulphate. Stillbirths and neonatal deaths were not reported. There are insufficient data for reliable conclusions about the comparative effects of any other drugs. Until better evidence is available the choice of antihypertensive should depend on the clinician's experience and familiarity with a particular drug; on what is known about adverse effects; and on women's preferences. Exceptions are nimodipine, magnesium sulphate (although this is indicated for women who require an anticonvulsant for prevention or treatment of eclampsia), diazoxide and ketanserin, which are probably best avoided. | During pregnancy, a woman's blood pressure falls in the first few weeks then rises again slowly from around the middle of pregnancy, reaching pre-pregnancy levels at term. Pregnant women with very high blood pressure (systolic over 160 mmHg, diastolic 110 mmHg or more) are at risk of developing pre-eclampsia with associated kidney failure and premature delivery, or of having a stroke. The review of 35 randomised controlled trials including 3573 women (in the mid to late stages of pregnancy, where stated) found that while antihypertensive drugs are effective in lowering blood pressure, there is not enough evidence to show which drug is the most effective. Fifteen different comparisons of antihypertensive treatments were included in these 35 trials, which meant that some comparisons were made by single trials. Only one trial had a large number of participants. This trial compared nimodipine with magnesium sulphate and showed that high blood pressure persisted in 47% and 65% of women, respectively. Calcium channel blockers were associated with less persistent hypertension than with hydralazine and possibly less side-effects compared to labetalol. There is some evidence that diazoxide may result in a woman's blood pressure falling too quickly, and that ketanserin may not be as effective as hydralazine. Further research into the effects of antihypertensive drugs during pregnancy is needed. |
Only two trials (60 participants) investigating the effect of metformin added to insulin therapy for three months in adolescents with poorly controlled type 1 diabetes could be included. Meta-analysis was not possible due to the clinical and methodological heterogeneity of data. Both studies suggested that metformin treatment lowered glycosylated haemoglobin A1c (HbA1c) in adolescents with type 1 diabetes and poor metabolic control. Improvements in insulin sensitivity, body composition or serum lipids were not documented in either study, however, one study showed a decrease in insulin dosage by 10%. Adverse effects were mainly gastrointestinal in both studies and hypoglycaemia in one study. No data on health-related quality of life, all-cause mortality or morbidity are currently available. There is some evidence suggesting improvement of metabolic control in poorly controlled adolescents with type 1 diabetes, on addition of metformin to insulin therapy. Stronger evidence is required from larger studies, carried out over longer time periods to document the long-term effects on metabolic control, health-related quality of life as well as morbidity and mortality in those patients. | Only two trials (60 participants, three months treatment) could be included. Both studies suggested that metformin plus insulin treatment lowered HbA1c somewhat more than placebo plus insulin. Improvement in insulin sensitivity, body weight or serum lipids were not seen in either study. However, one study showed a small decrease in insulin dosage by 10%. Side effects were mainly gastrointestinal upset in both studies and hypoglycaemia (low blood sugar) in one study. There was no information on health-related quality of life, costs, morbidity or mortality in either study. |
A total of 3239 citations were identified through the searches. Only one RCT, with 15-year follow-up met the inclusion criteria (n = 13 clusters: 191,873 participants). There was no statistically significant difference in the oral cancer mortality rates for the screened group (15.4/100,000 person-years) and the control group (17.1/100,000 person-years), with a RR of 0.88 (95% CI 0.69 to 1.12). A 24% reduction in mortality was reported between the screening group (30/100,000 person-years) and the control group (39.0/100,000) for high-risk individuals who used tobacco or alcohol or both, which was statistically significant (RR 0.76; 95% CI 0.60 to 0.97). No statistically significant differences were found for incidence rates. A statistically significant reduction in the number of individuals diagnosed with stage III or worse oral cancer was found for those in the screening group (RR 0.81; 95% CI 0.70 to 0.93). No harms were reported. The study was assessed as at high risk of bias. There is evidence that a visual examination as part of a population-based screening programme reduces the mortality rate of oral cancer in high-risk individuals. In addition, there is a stage shift and improvement in survival rates across the population as a whole. However, the evidence is limited to one study, which has a high risk of bias and did not account for the effect of cluster randomisation in the analysis. There was no evidence to support the use of adjunctive technologies like toluidine blue, brush biopsy or fluorescence imaging as a screening tool to reduce oral cancer mortality. Further RCTs are recommended to assess the efficacy and cost-effectiveness of a visual examination as part of a population-based screening programme in low, middle and high-income countries. | The evidence on which this review is based is up to date as of 22 July 2013. The only study included was based in rural areas of the city of Trivandrum in Kerala, India. The study included 191,873 apparently healthy adults aged 35 years or older living in 13 clusters with an average of 14,759 participants in each cluster. Screening took place in seven clusters (96,517 participants) and six clusters acted as a control (95,356 participants). Participants were excluded if they were bedridden, if they had open tuberculosis, other debilitating diseases or were already suffering from oral cancer. Healthcare workers trained in the detection of oral lesions undertook the screening of participants and the social history of participants including use of paan, tobacco, alcohol and dietary supplements was recorded. The review found that overall there is not enough evidence to decide whether screening by visual inspection reduces the death rate for oral cancer and there is no evidence for other screening methods. However, there is some evidence that it might help reduce death rates in patients who use tobacco and alcohol although the only included study may be affected by bias. The evidence presented is of low quality and limited to one study assessed as at high risk of bias. |
We identified three eligible trials involving a total of 222 participants with 333 groin wounds. Suction drainage was compared with no drainage in all studies. Two studies were parallel-group, randomized controlled trials, and one was a split-body, randomized controlled trial. Trial settings were not clearly described. Patients undergoing bypass and endarterectomy procedures were included, but none of the studies provided details on the severity of the underlying arterial disease. We deemed all of the studies to be at a high risk of bias in three or more domains of the 'Risk of bias' assessment and overall the evidence was of very low quality. Two out of three studies had unit of analysis errors (with multiple wounds within patients analysed as independent) and it was not possible to judge the appropriateness of the analysis of the third. Meta-analysis was not appropriate, firstly because of clinical heterogeneity, and secondly because we were not able to adjust for the analysis errors in the individual trials. One trial yielded data on surgical site infections (SSI; the primary outcome of the review): there was no clear difference between drained and non-drained wounds for SSI (risk ratio 1.33; 95% confidence interval 0.30 to 5.94; 50 participants with bilateral groin wounds; very low quality evidence). It was not possible to evaluate any other outcomes from this trial. The results from the other two studies are unreliable because of analysis errors and reporting omissions. The data upon which to base practice in this area are limited and prone to biases. Complete uncertainty remains regarding the potential benefits and harms associated with the use of wound drains in lower limb arterial surgery due to the small number of completed studies and weaknesses in their design and conduct. Higher quality evidence is needed to inform clinical decision making. To our knowledge, no trials on this topic are currently active. | In June 2016 we searched for randomised controlled trials (RCTs) involving the use of drains after leg artery surgery. We identified three eligible trials involving 333 wounds in 222 patients, mainly aged over 65, who had leg artery surgery. Both men and women were included and all of the wounds were in the groin area as part of bypass and endarterectomy operations to improve blood flow. The studies involved small numbers of patients and were not clearly described. All three studies had serious weaknesses in the way they were designed and performed. The results of the individual studies do not provide reliable information because of weaknesses in study design. It is unclear whether wound drains are beneficial or harmful because we did not find any useful information. None of the studies gave information on whether drains shortened or lengthened the number of days that patients had to spend in hospital. None of the studies gave information about how drains affect patients' quality of life. Overall, we found that the quality of the evidence about the effects of drains after leg artery surgery was very low and we were not able to tell whether drains lead to benefits or harms for patients. Better quality research is needed if patients and healthcare providers think that this is an important topic. This plain language summary is up to date as of 8 June 2016. |
We included 11 studies (674 participants). The risk of bias was high or unclear in all of the included studies. All studies compared needle aspiration to incision and drainage. All but one of the 11 studies reported on the primary outcome of recurrence. When we pooled data from the 10 studies the recurrence rate was higher in the needle aspiration group compared with incision and drainage: risk ratio (RR) 3.74 (95% confidence interval (CI) 1.63 to 8.59; 612 participants). We detected moderate heterogeneity in this analysis (I2 = 48%). In interpreting the pooled result it is important to note that the evidence for this outcome was of very low quality. None of the other outcomes (adverse effects of the intervention, time to resumption of normal diet, complications of the disease process and symptom scores) were consistently measured across all studies. Only three studies reported on adverse effects/events associated with the intervention and only one such event in a single patient was reported (post-procedure bleeding following incision and drainage: 1/28, 3.6%) (very low-quality evidence). Time to resumption of normal diet was compared in two studies; neither found an obvious difference between needle aspiration and incision and drainage (very low-quality evidence). Only three studies stated that they would report complications of the disease process. In these three studies, the only complication reported was admission to hospital for dehydration in two patients who underwent incision and drainage (2/13, 6.7%). Symptom scores were measured in four studies; three evaluated pain using different scales and one other symptoms. The data could not be pooled in a meta-analysis. Two studies evaluating procedural pain reported this to be lower in the needle aspiration groups. One study found comparable rates of pain resolution at five days post-intervention between groups. The quality of the evidence for symptom scores was very low. Although a number of studies have sought to evaluate whether or not needle aspiration or incision and drainage is more effective in patients with peritonsillar abscess, there is no high-quality evidence to allow a firm conclusion to be drawn and the answer remains uncertain. Very low-quality evidence suggests that incision and drainage may be associated with a lower chance of recurrence than needle aspiration. There is some very low-quality evidence to suggest that needle aspiration is less painful. | We included 11 studies with a total of 674 participants. The participants in the studies were aged from 8 to 79. The studies were conducted in a number of countries (six from Pakistan, two from the USA, one from Taiwan and two from South Africa). All but one of the 11 studies reported the difference in recurrence rate between needle aspiration and incision and drainage. Four studies compared symptom scores associated with the procedure and two studies compared time to resumption of normal diet. Three studies reported adverse effects/events associated with the intervention. Two studies reported complications of the disease process itself. The evidence is current to August 2016. Ten studies reported on the recurrence of peritonsillar abscess (our main outcome). Most of them did not clearly define 'recurrence' and they varied in the timing of its assessment, however we were able to combine (pool) the data from these studies. When we pooled the data the recurrence rate was higher in the needle aspiration group compared with incision and drainage. It is important to note that the evidence for this outcome was of very low quality. Some studies found that patients had more pain when they had incision and drainage. We identified problems or potential problems in all of the included studies. The most important of these was that the studies did not all assess recurrence in the same way, at the same time, using the same criteria. The quality of the evidence for all of the outcomes that we looked at was very low. |
We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ-5D-5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low-quality evidence). Investigators reported similar rates of clinically relevant non-major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate-quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ-5D-5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low-quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low-quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high-intensity warfarin treatment compared to the standard-intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low-quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high-intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high-intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. | The evidence is current to February 2017. We looked for studies that randomly allocated people with APS to different treatments, including anticoagulants, antiplatelets, or both. We identified five studies involving 419 participants. The average age of the participants was between 41 and 50 years, and the studies included people with previous stroke or previous blood clots in large veins or arteries. Studies took place in eight different countries and had a variety of funding sources. One trial compared a novel anticoagulant (rivaroxaban) with the standard anticoagulant (warfarin). Two studies compared a high dose versus standard dose of warfarin , and two studies compared combinations of antiplatelets, anticoagulants, or both. Interventions lasted from 180 days to an average of 3.9 years (SD 2.0). In one study with an anticoagulant (rivaroxaban), participants had no episodes of blood clotting, and there was no difference in the risk of bleeding (moderate-quality evidence). In the two studies comparing higher and lower doses of anticoagulant (warfarin), similar proportions of participants had blood clotting and major bleeding problems (low-quality evidence), but the higher dose warfarin group had a greater risk of minor bleeding problems and any bleeding problems (low-quality evidence). The two studies comparing combinations of antiplatelets and anticoagulants were both small, not well reported, and their results were inconclusive (very low-quality evidence). One study was well designed, and we judged it to be at low risk of bias; we judged a second study to be at low risk of bias for the main results. We considered all other studies to be at unclear or high risk of bias because of concerns about their methods or reporting of results. All the results were imprecise and did not clearly indicate benefit or harm. We did not find enough evidence in our review to judge the benefit or harm of using anticoagulant (rivaroxaban) versus anticoagulant (warfarin) for preventing blood clots or stroke in people with APS. Treatment with high doses of the anticoagulant warfarin was associated with a higher risk of minor and any bleeding than treatment with standard doses, but we found no difference in terms of benefit. There was not enough evidence to show benefit or harm of any combination of anticoagulants and/or antiplatelets. Five ongoing studies will likely provide additional evidence in the near future. |
We included six randomised clinical trials with 173 participants. All participants had Child-Pugh stage A or B cirrhosis. The intervention groups participated in eight to 14 weeks of physical exercise (aerobic: three trials; resistance: one trial; or aerobic plus resistance training: two trials). Control groups underwent sham exercise (supervised relaxation: one trial) or no intervention (five trials). None of the 89 participants allocated to exercise versus two of 84 participants in the control group died (RR 0.19, 95% CI 0.01 to 3.73; moderate-quality evidence). The cause of death was acute-on-chronic liver disease for both participants. Nine participants in the exercise group and 13 in the control group experienced serious adverse events (RR 0.61, 95% CI 0.19 to 1.94; low-quality evidence). Physical exercise showed no beneficial or detrimental effect on health-related quality of life assessed by the Chronic Liver Disease Questionnaire (MD 0.11, 95% CI –0.44 to 0.67; low-quality evidence). Likewise, physical exercise had no clear effect on physical fitness measured by peak exercise oxygen uptake (MD 0.3 mL/kg/minute, 95 % CI –2.74 to 3.35; low-quality evidence) and Six-Minute Walk Test (MD 56.06 min, 95% CI –9.14 to 121.26; very low-quality evidence). Physical exercise showed no clear effect on mid-thigh circumference (MD 1.76 cm, 95% CI –0.26 to 3.77; low-quality evidence), but showed an increase in mid-arm circumference (MD 2.61 cm, 95% CI 0.36 to 4.85; low-quality evidence). We found no clear beneficial or harmful effect of physical exercise on mortality, morbidity, or health-related quality of life. Further evidence is needed to evaluate the beneficial and harmful effects of physical exercise on clinical outcomes. | We included six randomised clinical trials (where people are randomly allocated to one of two groups) with 173 participants. All participants had cirrhosis. Interventions consisted of different types of exercise including bicycling, treadmill walking, and weight lifting. Programmes were home-based or supervised and lasted between eight and 14 weeks. Physical exercise did not seem to affect mortality (death), side effects or quality of life. Overall, the evidence for the effect of physical exercise was of low or very low quality. Factors that downgraded the quality of the evidence included lack of trials with a low risk of bias, small trials, and not similar results across trials. |
We included four RCTs with a total of 453 participants and determined that none of these trials had overall low risk of bias. We found six ongoing trials from which we were unable to retrieve further data. Three trials provided data on mortality. Meta-analysis showed no statistical effect on overall mortality (RR 0.93, 95% CI 0.37 to 2.33; very low quality of evidence). We were unable to associate use of PCC with the number of complications probably related to the intervention (RR 0.92, 95% CI 0.78 to 1.09; very low quality of evidence). Lack of transfusion data and apparent differences in study design prevented review authors from finding a beneficial effect of PCC in reducing the volume of fresh frozen plasma (FFP) transfused to reverse the effect of vitamin K antagonist treatment. The number of new occurrences of transfusion of red blood cells (RBCs) did not seem to be associated with the use of PCC (RR 1.08, 95% CI 0.82 to 1.43; very low quality of evidence). Still, the included studies demonstrate the possibility of equally reversing vitamin K-induced coagulopathy using PCC without the need for transfusion of FFP. No effect on other predefined outcomes was observed. In the four included RCTs, use of prothrombin complex concentrate does not appear to reduce mortality or transfusion requirements but demonstrates the possibility of reversing vitamin K-induced coagulopathy without the need for transfusion of fresh frozen plasma. All included trials have high risk of bias and are underpowered to detect mortality, benefit or harm. Clinical and statistical heterogeneity is high, and definitions of clinically important outcomes such as adverse events are highly dissimilar between trials. Only weak observational evidence currently supports the use of PCC in vitamin K antagonist-treated bleeding and non-bleeding patients, and the current systematic review of RCTs does not support the routine use of PCC over FFP. Additional high-quality research is urgently needed. | In the present Cochrane systematic review, we assessed the benefits and harms of prothrombin complex concentrate in vitamin K antagonist-treated bleeding and non-bleeding patients who are undertaking acute surgical intervention. We searched the databases until 1 May 2013. We identified four randomized trials (453 participants) involving neurological and cardiac surgical settings, as well as medical reversal of vitamin K-intoxication among participants. We found six ongoing trials but were unable to retrieve these data. We reran the search in October 2014 and found one new study of potential interest. We added this study to a list of ‘Studies awaiting classification', and we will incorporate this study into the formal review findings at the time of the review update. We could not identify any beneficial effects of prothrombin complex concentrate on death. In our predefined outcomes, we identified a decreased volume of fresh frozen plasma transfused for reversal of vitamin K antagonist treatment. We could not identify statistical differences in reduced blood loss, harm or numbers of adverse events in the group treated with PCC. However, all trials were of low quality and small, and all were characterized by a high level of heterogeneity. Therefore, evidence in support of PCC in vitamin K antagonist-treated bleeding and non-bleeding patients receiving acute surgical intervention remains weak. |
We included 32 studies that involved a total of 2601 participants. Acupuncture was either manually stimulated (24 studies) or electrically stimulated (8 studies). The aetiology of gastroparesis was diabetes (31 studies) or surgery (1 study). All studies provided data on the proportion of people with symptoms 'improved', although the definition or categorisation of improvement varied among the studies. Most measured only short-term outcomes (28 studies), and only one study employed validated instruments to assess subjective changes in symptoms or reported data on quality of life or the use of medication. Reporting of harm was incomplete; minor adverse events were reported in only seven trials. Most studies had unclear risk of bias in terms of allocation concealment (29/32), outcome assessor blinding (31/32) and selective reporting (31/32), as well as high risk of bias in terms of participant/personnel blinding (31/32). Acupuncture was compared with sham acupuncture (needling on non-acupuncture points), three different types of gastrokinetic drugs (domperidone, mosapride, cisapride), and a histamine H₂ receptor antagonist (cimetidine). There was low-certainty evidence that symptom scores of participants receiving acupuncture did not differ from those of participants receiving sham acupuncture at three months when measured by a validated scale. There was very low-certainty evidence that a greater proportion of participants receiving acupuncture had 'improved' symptoms in the short term compared to participants who received gastrokinetic medication (4 to 12 weeks) (12 studies; 963 participants; risk ratio (RR) 1.25; 95% confidence interval (CI) 1.17 to 1.33, I² = 8%). Short-term improvement in overall symptom scores favouring acupuncture was also reported in five studies with considerable heterogeneity. Acupuncture in combination with other treatments, including gastrokinetics, non-gastrokinetics and routine care, was compared with the same treatment alone. There was very low-certainty evidence in favour of acupuncture for the proportion of participants with 'improved' symptoms in the short term (4 to 12 weeks) (17 studies; 1404 participants; RR 1.22; 95% CI 1.16 to 1.28; I² = 0%). Short-term improvement in overall symptom scores, favouring acupuncture, were also reported (two studies, 132 participants; MD -1.96, 95% CI -2.42 to -1.50; I² = 0%). Seven studies described adverse events, including minor bleeding and hematoma, dizziness, xerostomia, loose stool, diarrhoea, abdominal pain, skin rash and fatigue. The rest of the trials did not report whether adverse events occurred. Subgroup analyses revealed that short-term benefits in terms of the proportion of people with 'improved' symptoms did not differ according to the type of acupuncture stimulation (i.e. manual or electrical). The sensitivity analysis revealed that use of a valid method of random sequence generation, and the use of objective measurements of gastric emptying, did not alter the overall effect estimate in terms of the proportion of people with 'improved' symptoms. The asymmetric funnel plot suggests small study effects and publication bias towards positive reporting. There is very low-certainty evidence for a short-term benefit with acupuncture alone or acupuncture combined with gastrokinetic drugs compared with the drug alone, in terms of the proportion of people who experienced improvement in diabetic gastroparesis. There is evidence of publication bias and a positive bias of small study effects. The reported benefits should be interpreted with great caution because of the unclear overall risk of bias, unvalidated measurements of change in subjective symptoms, publication bias and small study reporting bias, and lack of data on long-term outcomes; the effects reported in this review may therefore differ significantly from the true effect. One sham-controlled trial provided low-certainty evidence of no difference between real and sham acupuncture in terms of short-term symptom improvement in diabetic gastroparesis, when measured by a validated scale. No studies reported changes in quality of life or the use of medication. Due to the absence of data, no conclusion can be made regarding effects of acupuncture on gastroparesis of other aetiologies. Reports of harm have remained largely incomplete, precluding assessments of the safety of acupuncture in this population. Future research should focus on reducing the sources of bias in the trial design as well as transparent reporting. Harms of interventions should be explicitly reported. | We analysed 32 studies that involved a total of 2601 participants. Most trials involved people with diabetic gastroparesis, who received short-term treatment (often four weeks). Non-profit funding bodies (the Chinese government and a university) funded six out of the 32 studies and the others did not report the funding source. One study compared real acupuncture with sham acupuncture (needling on non-acupuncture points). Twenty-eight trials compared acupuncture to a drug, or acupuncture with a drug or to the drug alone. A small number of trials compared acupuncture plus a non-drug treatment to the same treatment alone. The drugs in the trials were mostly gastrokinetic agents (such as domperidone, mosapride, and cisapride), which promote stomach emptying. Despite there being a small reported effect, we are uncertain about any benefit of acupuncture for symptomatic gastroparesis in the short term, when used alone or added to other treatments for gastroparesis (gastrokinetics, other medicines, or 'routine care'), due to the evidence being of very low certainty. There is no information to help understand any long-term benefits of acupuncture. The effects of acupuncture on symptoms of gastroparesis are probably little different from those of sham acupuncture in the short term. It is unclear whether acupuncture helps in gastroparesis after surgery or when the cause of gastroparesis is unknown, because there is not enough information. No trial studied the effects of acupuncture on quality of life or delayed emptying of the stomach. We do not know whether acupuncture is safe for people with diabetes who have delayed emptying of the stomach, because safety was incompletely reported in most trials. Overall, the certainty of evidence is very low. Most studies had design issues. We suspected the existence of unpublished studies and it was not possible to be sure whether those we identified fully reported their findings. There was no consistent definition of improvement across studies. Any reported benefit may not be accurate and should be interpreted with caution. Future trials should focus on valid measures of treatment effects reported directly by patients, and assessment of stomach emptying. Trials should meet quality standards for design and transparent reporting. The evidence is current to March 2018. |
We included 12 RCTs (743 people). Among these RCTs, flexibility exercise training was compared to an untreated control group, land-based aerobic training, resistance training, or other interventions (i.e. Tai Chi, Pilates, aquatic biodanza, friction massage, medications). Studies were at risk of selection, performance, and detection bias (due to lack of adequate randomization and allocation concealment, lack of participant or personnel blinding, and lack of blinding for self-reported outcomes). With the exception of withdrawals and adverse events, major outcomes were self-reported and were expressed on a 0-to-100 scale (lower values are best, negative mean differences (MDs) indicate improvement). We prioritized the findings of flexibility exercise training compared to land-based aerobic training and present them fully here. Very low-certainty evidence showed that compared with land-based aerobic training, flexibility exercise training (five trials with 266 participants) provides no clinically important benefits with regard to HRQoL, pain intensity, fatigue, stiffness, and physical function. Low-certainty evidence showed no difference between these groups for withdrawals at completion of the intervention (8 to 20 weeks). Mean HRQoL assessed on the Fibromyalgia Impact Questionnaire (FIQ) Total scale (0 to 100, higher scores indicating worse HRQoL) was 46 mm and 42 mm in the flexibility and aerobic groups, respectively (2 studies, 193 participants); absolute change was 4% worse (6% better to 14% worse), and relative change was 7.5% worse (10.5% better to 25.5% worse) in the flexibility group. Mean pain was 57 mm and 52 mm in the flexibility and aerobic groups, respectively (5 studies, 266 participants); absolute change was 5% worse (1% better to 11% worse), and relative change was 6.7% worse (2% better to 15.4% worse). Mean fatigue was 67 mm and 71 mm in the aerobic and flexibility groups, respectively (2 studies, 75 participants); absolute change was 4% better (13% better to 5% worse), and relative change was 6% better (19.4% better to 7.4% worse). Mean physical function was 23 points and 17 points in the flexibility and aerobic groups, respectively (1 study, 60 participants); absolute change was 6% worse (4% better to 16% worse), and relative change was 14% worse (9.1% better to 37.1% worse). We found very low-certainty evidence of an effect for stiffness. Mean stiffness was 49 mm to 79 mm in the flexibility and aerobic groups, respectively (1 study, 15 participants); absolute change was 30% better (8% better to 51% better), and relative change was 39% better (10% better to 68% better). We found no evidence of an effect in all-cause withdrawal between the flexibility and aerobic groups (5 studies, 301 participants). Absolute change was 1% fewer withdrawals in the flexibility group (8% fewer to 21% more), and relative change in the flexibility group compared to the aerobic training intervention group was 3% fewer (39% fewer to 55% more). It is uncertain whether flexibility leads to long-term effects (36 weeks after a 12-week intervention), as the evidence was of low certainty and was derived from a single trial. Very low-certainty evidence indicates uncertainty in the risk of adverse events for flexibility exercise training. One adverse effect was described among the 132 participants allocated to flexibility training. One participant had tendinitis of the Achilles tendon (McCain 1988), but it is unclear if the tendinitis was a pre-existing condition. When compared with aerobic training, it is uncertain whether flexibility improves outcomes such as HRQoL, pain intensity, fatigue, stiffness, and physical function, as the certainty of the evidence is very low. Flexibility exercise training may lead to little or no difference for all-cause withdrawals. It is also uncertain whether flexibility exercise training has long-term effects due to the very low certainty of the evidence. We downgraded the evidence owing to the small number of trials and participants across trials, as well as due to issues related to unclear and high risk of bias (selection, performance, and detection biases). While flexibility exercise training appears to be well tolerated (similar withdrawal rates across groups), evidence on adverse events was scarce, therefore its safety is uncertain. | We searched the literature up to December 2017 and found 12 studies (743 individuals) that met our inclusion criteria. Flexibility interventions were compared with control (treatment as usual), aerobic training interventions (e.g. treadmill walking), resistance-training interventions (e.g. using weight machines that provide resistance to movement), and other interventions (e.g. Pilates). The average age of participants was 48.6 years. Trials were conducted in seven countries, and most studies (58.3%) included only female participants. Exercise trials ranged from 4 to 20 weeks. The stretching exercise programs ranged from 40 to 60 minutes, 1 to 3 times a day. The intensity of the stretches (e.g. how far the stretch was taken in the available range of motion) was not reported in most cases. The time each stretch was held ranged from 6 to 60 seconds. The targeted muscles were usually of both the upper and lower extremities, neck, and back. The flexibility training was either supervised or done at home. Our main comparison was flexibility exercise versus land-based aerobic training. Key results at the end of treatment for our main comparison Compared with land-based aerobic exercise training, flexibility exercise resulted in little benefit at 8 to 20 weeks' follow-up. Each measure below was measured on a scale from 0 to 100, with lower scores better. Health-related quality of life: People who received flexibility exercise training were 4% worse (ranging from 6% better to 14% worse). • People who had flexibility training rated their quality of life as 46 points. • People who had aerobic training rated their quality of life as 42 points. Pain intensity: People who received flexibility exercise training were 5% worse (ranging from 1% better to 11% worse). • People who had flexibility training rated their pain as 57 points. • People who had aerobic training rated their pain as 52 points. Fatigue: People who received flexibility exercise training were 4% better (ranging from 13% better to 5% worse). • People who had flexibility training rated their fatigue as 67 points. • People who had aerobic training rated their fatigue as 71 points. Stiffness: People who received flexibility exercise training were 30% better (ranging from 8% better to 51% better). • People who had flexibility training rated their stiffness as 49 points. • People who had aerobic training rated their stiffness as 79 points. Physical function: People who received flexibility exercise training were 6% worse (ranging from 4% better to 16% worse). • People who had flexibility training rated their physical function as 23 points. • People who had aerobic training rated their physical function as 17 points. Withdrawal from treatment A total of 18 per 100 people dropped out of the flexibility exercise training group for any reason compared to 19 per 100 people from the aerobic training group. Harms We found no clear information on harms. One study reported that one participant had swelling (tendinitis) of an ankle tendon (Achilles), but it is unclear if this was related to participation in the flexibility exercise. Quality of evidence The evidence does not show that flexibility exercise significantly improves health-related quality of life, pain, fatigue, or physical function. The number of people dropping out from each group was similar. Although the evidence suggests that flexibility exercise improves stiffness, caution is advised in interpretation of these results, as this improvement was seen in only one study with very few participants. We considered the overall certainty of the evidence to be low to very low due to study design issues, the small number of participants, and low certainty of results. |
We identified three trials (κ = 1.00) involving 1272 participants. Comparing the capnography group to the standard monitoring group, there were no differences in the rates of oxygen desaturation (RR 0.89, 95% CI 0.48 to 1.63; n = 1272, 3 trials; moderate quality evidence) and hypotension (RR 2.36, 95% CI 0.98 to 5.69; n = 986, 1 trial; moderate quality evidence). There was only one episode of emesis recorded without significant difference between the groups (RR 3.10, 95% CI 0.13 to 75.88, n = 986, 1 trial; moderate quality evidence). The quality of evidence for the primary outcomes was moderate with downgrades primarily due to heterogeneity and reporting bias. There were no differences in the rate of airway interventions performed (RR 1.26, 95% CI 0.94 to 1.69; n = 1272, 3 trials; moderate quality evidence). In the subgroup analysis, we found a higher rate of airway interventions for adults in the capnography group (RR 1.44, 95% CI 1.16 to 1.79; n = 1118, 2 trials; moderate quality evidence) with a number needed to treat for an additional harmful outcome of 12. Although statistical heterogeneity was reduced, there was moderate quality of evidence due to outcome definition heterogeneity and limited reporting bias. None of the studies reported recovery time. There is a lack of convincing evidence that the addition of capnography to standard monitoring in ED PSA reduces the rate of clinically significant adverse events. Evidence was deemed to be of moderate quality due to population and outcome definition heterogeneity and limited reporting bias. Our review was limited by the small number of clinical trials in this setting. | We searched for studies using multiple research databases, conference research abstracts, and by contacting experts in the field. The evidence is current to August 2016. We only considered studies with participants being sedated for procedures in the emergency department. We only included studies that compared capnography and standard monitoring to standard monitoring only. The main outcomes involved events of low blood oxygen content, low blood pressure, and vomiting. We also recorded how many times the healthcare providers had to help the patient breathe easier. This could mean simple actions such as opening of the mouth to more serious manoeuvres such as mechanically breathing for the patient. Three studies with 1272 people, containing moderate evidence, were included in our study. There was no difference in heart, lung, or airway complications with the addition of capnography. When only adults were studied, healthcare providers performed more manoeuvres to help the patient breathe when capnography was used. This could be due to false alarms. The level of evidence was determined to be moderate. |
We included 38 RCTs. Twenty-two had a split-mouth design, and 16 had a parallel design. The overall evaluated data included 1402 defects. Two studies were at unclear overall risk of bias, while the remaining 36 studies had a high overall risk of bias. 1. APC + OFD versus OFD alone Twelve studies were included in this comparison, with a total of 510 infrabony defects. There is evidence of an advantage in using APC globally from split-mouth and parallel studies for all three primary outcomes: PD (mean difference (MD) 1.29 mm, 95% confidence interval (CI) 1.00 to 1.58 mm; P < 0.001; 12 studies; 510 defects; very low-quality evidence); CAL (MD 1.47 mm, 95% CI 1.11 to 1.82 mm; P < 0.001; 12 studies; 510 defects; very low-quality evidence); and RBF (MD 34.26%, 95% CI 30.07% to 38.46%; P < 0.001; 9 studies; 401 defects; very low-quality evidence). 2. APC + OFD + BG versus OFD + BG Seventeen studies were included in this comparison, with a total of 569 infrabony defects. Considering all follow-ups, as well as 3 to 6 months and 9 to 12 months, there is evidence of an advantage in using APC from both split-mouth and parallel studies for all three primary outcomes: PD (MD 0.54 mm, 95% CI 0.33 to 0.75 mm; P < 0.001; 17 studies; 569 defects; very low-quality evidence); CAL (MD 0.72 mm, 95% CI 0.43 to 1.00 mm; P < 0.001; 17 studies; 569 defects; very low-quality evidence); and RBF (MD 8.10%, 95% CI 5.26% to 10.94%; P < 0.001; 11 studies; 420 defects; very low-quality evidence). 3. APC + GTR versus GTR alone Seven studies were included in this comparison, with a total of 248 infrabony defects. Considering all follow-ups, there is probably a benefit for APC for both PD (MD 0.92 mm, 95% CI -0.02 to 1.86 mm; P = 0.05; very low-quality evidence) and CAL (MD 0.42 mm, 95% CI -0.02 to 0.86 mm; P = 0.06; very low-quality evidence). However, given the wide confidence intervals, there might be a possibility of a slight benefit for the control. When considering a 3 to 6 months and a 9 to 12 months follow-up there were no benefits evidenced, except for CAL at 3 to 6 months (MD 0.54 mm, 95% CI 0.18 to 0.89 mm; P = 0.003; 3 studies; 134 defects). No RBF data were available. 4. APC + EMD versus EMD Two studies were included in this comparison, with a total of 75 infrabony defects. There is insufficient evidence of an overall advantage of using APC for all three primary outcomes: PD (MD 0.13 mm, 95% CI -0.05 to 0.30 mm; P = 0.16; 2 studies; 75 defects; very low-quality evidence), CAL (MD 0.10 mm, 95% CI -0.13 to 0.32 mm; P = 0.40; 2 studies; 75 defects; very low-quality evidence), and RBF (MD -0.60%, 95% CI -6.21% to 5.01%; P = 0.83; 1 study; 49 defects; very low-quality evidence). All studies in all groups reported a survival rate of 100% for the treated teeth. No complete pocket closure was reported. No quantitative analysis regarding patients' quality of life was possible. There is very low-quality evidence that the adjunct of APC to OFD or OFD + BG when treating infrabony defects may improve probing pocket depth, clinical attachment level, and radiographic bone defect filling. For GTR or EMD, insufficient evidence of an advantage in using APC was observed. | Authors from Cochrane Oral Health carried out this review and the evidence is up to date to 27 February 2018. We included 38 studies and a total of 1042 infrabony defects. We considered four different types of surgical treatments and compared each technique with the same one when APC was added. Overall we considered these comparisons: open flap debridement with APC versus without APC; open flap debridement and bone graft with APC versus without APC; guided tissue regeneration with APC versus without APC; and enamel matrix derivative with APC versus without APC. There is very low-quality evidence that the addition of APC to two types of treatment: open flap debridement and open flap debridement with bone graft, may bring some advantages in the treatment of infrabony defects. However, for the other two types of treatment, guided tissue regeneration and enamel matrix derivative, there is insufficient evidence of a benefit. We judged the quality of the evidence to be very low due to problems with the design of the studies. |
Five RCTs with 202 participants met the inclusion criteria. The women participants were typically in their 50s, and the majority of them (about 82%) received reconstructive surgery following breast cancer, while the others had reconstructive surgery after prophylactic mastectomy. The studies were heterogenous in terms of implant comparisons, which prevented us from pooling the data. The studies were judged as being at an unclear risk of bias for most risk of bias items owing to poor quality of reporting in the trial publications. Three of the five RCTs were judged to be at high risk of attrition bias, and one at high risk of detection bias. Textured silicone versus smooth silicone implants: textured implants were associated with worse outcomes when compared to smooth implants (capsular contracture: risk ratio (RR) 0.82, 95% CI 0.14 to 4.71; 1 study, 20 participants; very low quality evidence; reintervention: RR 0.82, 95% CI 0.14 to 4.71; 1 study, 20 participants; very low quality evidence). No results in this comparison were statistically significant. Silicone versus saline implants: saline-filled implants performed better than silicone-filled implants for some outcomes; specifically, they produced less severe capsular contracture (RR 3.25, 95% CI 1.24 to 8.51; 1 study, 60 participants; very low quality evidence) and increased patient satisfaction (RR 0.60, 95% CI 0.41 to 0.88; 1 study, 58 participants; very low quality evidence). However reintervention was significantly more frequent in the saline-filled implant group than in the silicone-filled group (OR 0.08, 95% CI 0.01 to 0.43; 1 study, 60 participants; very low quality evidence). Poly(N-vinyl-2-pyrrolidone) hydrogel-filled (PVP-hydrogel) versus saline-filled implants: PVP-hydrogel-filled implants were associated with worse outcomes when compared to saline-filled implants (capsular contracture: RR 3.50, 95% CI 0.83 to 14.83; 1 study, 40 participants; very low quality evidence; short-term complications: RR 2.10, 95% CI 0.21 to 21.39; 1 study, 41 participants; very low quality evidence). Anatomical versus round implants: anatomical implants were associated with worse outcomes than round implants (capsular contracture: RR 2.00, 95% CI 0.20 to 20.15; 1 study, 36 participants; very low quality evidence; short-term complications: RR 2.00, 95% CI 0.42 to 9.58; 1 study, 36 participants; very low quality evidence; reintervention: RR 1.50, 95% CI 0.51 to 4.43; 1 study, 36 participants; very low quality evidence). No results in this comparison were statistically significant. Variable-volume versus fixed-volume implants: data about one-stage reconstruction using variable-volume implants were compared with data about fixed-volume implants positioned during the second surgical procedure of two-stage reconstructions. Fixed-volume implant reconstructions were possibly associated with a greater number of women reporting that their reconstruction corresponded with expected results (RR 0.25, 95% CI 0.10 to 0.62; 1 study, 40 participants; very low quality evidence) and fewer reinterventions (RR 7.00, 95% CI 1.82 to 26.89; 1 study, 40 participants; very low quality evidence) when compared to variable-volume implants. A higher patient satisfaction level (rated from 1 to 6, with 1 being very bad and 6 being very good) was found with the fixed-volume implants for overall aesthetic result (mean difference (MD) -1.10, 95% CI -1.59 to -0.61; 1 study, 40 participants; very low quality evidence). There were no studies that examined the effects of recent (fifth) generation silicone implants versus previous generations or different implant manufacturing companies. Despite the central role of breast reconstruction in women with breast cancer, the best implants to use in reconstructive surgery have been studied rarely in the context of RCTs. Furthermore the quality of these studies and the overall evidence they provide is largely unsatisfactory. Some of our results can be interpreted as early evidence of potentially large differences between different surgical approaches, which should be confirmed in new high-quality RCTs that include a larger number of women. These days - even after a few million women have had breasts reconstructed - surgeons cannot inform women about the risks and complications of different implant-based breast reconstructive options on the basis of results derived from RCTs. | The evidence is current to July 2015. We conducted a review to compare short- and long-term surgical complications (such as scar tissue forming around the implant and squeezing it - referred to as 'capsular contracture', and 'implant rupture'), cosmetic outcomes, women's postoperative quality of life and satisfaction with different types of breast implants used in breast reconstruction. We found five randomised studies involving 202 women that provided data for five different comparisons: rough versus smooth surface, implant filler materials compared to each other (silicone versus saline, and hydrogel versus saline), anatomical versus round shape, and variable- versus fixed-volume. Four studies included women who received a mastectomy for breast cancer and one study included women who had bilateral mastectomies for preventive purposes. The authors of two studies reported that they did not have competing interests; the authors of three studies did not report this information. Three studies reported that their studies received financial support from research foundations; the other studies did not report any information regarding the source of their funding. Only two studies reported differences between types of implants for some of the outcomes we considered. One study on 65 women compared silicone-filled implants with saline-filled implants and showed that saline implants resulted in fewer cases of capsular contracture and a higher number of women who were satisfied with the reconstructed breast. However more women in the saline-filled implant group required further operations on the reconstructed breast than in the silicone-filled implant group. Another study on 40 women compared variable-volume implants (inserted in a single surgical procedure) with fixed-volume implants (inserted in the second of two separate surgical procedures) and showed that there were significantly higher satisfaction levels and significantly lower reoperation rates with the fixed-volume implants. The remaining three studies reported on the following comparisons: rough versus smooth silicone-filled implants (20 women), PVP-hydrogel versus saline-filled implants (41 women) and anatomically shaped versus round implants (36 women). These studies reported no differences between implant types for outcomes such as capsular contracture, other short-term complications or reoperation rates. There were no studies that compared recent generation silicone implants with earlier versions or implants from different manufacturing companies. The evidence we found was limited: only a negligible, tiny fraction of women who undergo breast reconstruction have been studied in randomised controlled trials. The quality of evidence is very low, as the studies we identified suffered from major methodological limitations. Despite the fact that several million women have had their breasts reconstructed over the last 20 years, the small number of studies and the low numbers of women included in these studies does not allow us to draw any definitive conclusions about the which is the best type of breast implant. This lack of evidence should be discussed when informing women about the risks and complications of different implant-based breast reconstruction options. There is a need for further studies, which include a larger number of women and compare different types of implants, to free women from decisions made on the basis of surgical opinion alone. |
Ten trials (9 RCTs and 1 CCT) (954 participants and 73 caregivers) met the inclusion criteria. Eight RCTs scored well; while one RCT and one CCT scored poorly on the methodological quality assessment. Despite no change in the level of impairment, there was ’strong evidence’ to support inpatient MD rehabilitation in producing short-term gains at the levels of activity (disability) and participation in patients with MS. There is ‘moderate evidence’ to support inpatient or outpatient rehabilitation programmes (compared with control wait-list groups) in improving disability; and bladder related activity and participation outcomes up to 12 months following MD rehabilitation intervention. For outpatient and home-based rehabilitation programmes there was 'limited evidence' for short-term improvements in symptoms and disability with high intensity programmes, which translated into improvement in participation and quality of life. For low intensity programmes conducted over a longer period there was 'strong evidence' for longer-term gains in quality of life; and also 'limited evidence' for benefits to carers. Although some studies reported potential for cost-savings, there is no convincing evidence regarding the long-term cost-effectiveness of these programmes. It was not possible to suggest best 'dose' of therapy or supremacy of one therapy over another. This review highlights the limitations of RCTs in rehabilitation settings and need for better designed randomized and multiple centre trials. MD rehabilitation programmes do not change the level of impairment, but can improve the experience of people with MS in terms of activity and participation. Regular evaluation and assessment of these persons for rehabilitation is recommended. Further research into appropriate outcome measures, optimal intensity, frequency, cost and effectiveness of rehabilitation therapy over a longer time period is needed. Future research in rehabilitation should focus on improving methodological and scientific rigour of clinical trials. | This review looked for evidence of MD rehabilitation in adults with multiple sclerosis. The authors concluded there was strong evidence that inpatient or outpatient rehabilitation can lead to improvement in activity (disability) and in overall ability to participate in society, even though there is no reduction in actual impairment. There was limited evidence for short-term improvements in symptoms and disability, and in participation and quality of life with the high intensity outpatient and home-based rehabilitation programmes. For low intensity programmes conducted over a longer period there were longer term gains in quality of life; and for benefits to carers in terms of general health and engagement in social activities. The evidence available for other aspects of MD rehabilitation, including outpatient and home based therapy is not yet sufficient to allow many conclusions to be drawn. |
The search retrieved 16 studies (from 17 reports). Ten studies were excluded and one study is awaiting assessment. We included five studies involving 1065 women (1090 recruited). The five included studies were at moderate risk of bias. Data relating to one of our primary outcomes (UTI) was reported in four studies but did not meet our definition of UTI (as prespecified in our protocol). The included studies did not report on our other primary outcome – intraoperative bladder injury (this outcome was not prespecified in our protocol). Two secondary outcomes were not reported in the included studies: need for postoperative analgesia and women’s satisfaction. The included studies did provide limited data relating to this review’s secondary outcomes. Indwelling bladder catheter versus no catheter - three studies (840 women) Indwelling bladder catheterisation was associated with a reduced incidence of bladder distension (non-prespecified outcome) at the end of the operation (risk ratio (RR) 0.02, 95% confidence interval (CI) 0.00 to 0.35; one study, 420 women) and fewer cases of retention of urine (RR 0.06, 95% CI 0.01 to 0.47; two studies, 420 women) or need for catheterisation (RR 0.03, 95% CI 0.01 to 0.16; three studies 840 participants). In contrast, indwelling bladder catheterisation was associated with a longer time to first voiding (mean difference (MD) 16.81 hours, 95% CI 16.32 to 17.30; one study, 420 women) and more pain or discomfort due to catheterisation (and/or at first voiding) (average RR 10.47, 95% CI 4.71 to 23.25, two studies, 420 women) although high levels of heterogeneity were observed. Similarly, compared to women in the ‘no catheter’ group, indwelling bladder catheterisation was associated with a longer time to ambulation (MD 4.34 hours, 95% CI 1.37 to 7.31, three studies, 840 women) and a longer stay in hospital (MD 0.62 days, 95% CI 0.15 to 1.10, three studies, 840 women). However, high levels of heterogeneity were observed for these two outcomes and the results should be interpreted with caution. There was no difference in postpartum haemorrhage (PPH) due to uterine atony. There was also no difference in the incidence of UTI (as defined by trialists) between the indwelling bladder catheterisation and no catheterisation groups (two studies, 570 women). However, high levels of heterogeneity were observed for this non-prespecified outcome and results should be considered in this context. Indwelling bladder catheter versus bladder drainage – two studies (225 women) Two studies (225 women) compared the use of an indwelling bladder catheter versus bladder drainage. There was no difference between groups in terms of retention of urine following CS, length of hospital stay or the non-prespecified outcome of UTI (as defined by the trialist). There is some evidence (from one small study involving 50 women), that the need for catheterisation was reduced in the group of women with an indwelling bladder catheter (RR 0.04, 95% CI 0.00 to 0.70) compared to women in the bladder drainage group. Evidence from another small study (involving 175 women) suggests that women who had an indwelling bladder catheter had a longer time to ambulation (MD 0.90, 95% CI 0.25 to 1.55) compared to women who received bladder drainage. This review includes limited evidence from five RCTs of moderate quality. The review's primary outcomes (bladder injury during operation and UTI), were either not reported or reported in a way not suitable for our analysis. The evidence in this review is based on some secondary outcomes, with heterogeneity present in some of the analyses. There is insufficient evidence to assess the routine use of indwelling bladder catheters in women undergoing CS. There is a need for more rigorous RCTs, with adequate sample sizes, standardised criteria for the diagnosis of UTI and other common outcomes. | This review is based on five studies involving 1065 women undergoing CS. The studies were of moderate quality. The included studies did not use this review's criteria for diagnosis for UTI, so there are no data for this primary outcome. When considering UTI, as defined by the trial authors, there were no clear differences between groups. There were no data relating to bladder injury during the CS (the review's other primary outcome). Our analysis showed that the use of urinary catheter was associated with less retention of urine after CS. On the other hand, pain/discomfort due to catheterisation or at first voiding after CS, time to ambulate and hospital stay favoured non-use of urinary catheter. There was no difference in the incidence of uterine bleeding due to uterine atony (relaxation of the uterus) after the delivery. The limited evidence in this review is based five trials of moderate quality and results should be considered in this context. There is not enough evidence to assess the routine use of indwelling bladder catheters in women undergoing CS. There is a need for more rigorous research on this topic and future trials should use a standardised criteria for the diagnosis of UTI and other common outcomes. |
We included 50 trials involving 6510 women. Investigators compared oral antioxidants, including combinations of antioxidants, N-acetyl-cysteine, melatonin, L-arginine, myo-inositol, D-chiro-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, pentoxifylline and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant. Very low-quality evidence suggests that antioxidants may be associated with an increased live birth rate compared with placebo or no treatment/standard treatment (OR 2.13, 95% CI 1.45 to 3.12, P > 0.001, 8 RCTs, 651 women, I2 = 47%). This suggests that among subfertile women with an expected live birth rate of 20%, the rate among women using antioxidants would be between 26% and 43%. Very low-quality evidence suggests that antioxidants may be associated with an increased clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.52, 95% CI 1.31 to 1.76, P < 0.001, 26 RCTs, 4271 women, I2 = 66%). This suggests that among subfertile women with an expected clinical pregnancy rate of 22%, the rate among women using antioxidants would be between 27% and 33%. Heterogeneity was moderately high. There was insufficient evidence to determine whether there was a difference between the groups in rates of miscarriage (OR 0.79, 95% CI 0.58 to 1.08, P = 0.14, 18 RCTs, 2834 women, I2 = 23%, very low quality evidence). This suggests that, among subfertile women with an expected miscarriage rate of 7%, use of antioxidants would be expected to result in a miscarriage rate of between 4% and 7%. There was also insufficient evidence to determine whether there was a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.73 to 1.38, P = 0.98, 8 RCTs, 2163 women, I2 = 4%, very low quality evidence). This suggests that among subfertile women with an expected multiple pregnancy rate of 8%, use of antioxidants would be expected to result in a multiple pregnancy rate between 6% and 11%. Likewise, there was insufficient evidence to determine whether there was a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10, P = 0.47, 3 RCTs, 343 women, I2 = 0%, very low quality evidence). This suggests that among subfertile women with an expected gastrointestinal disturbance rate of 2%, use of antioxidants would be expected to result in a rate between 1% and 11%. Overall adverse events were reported by 35 trials in the meta-analysis, but there was insufficient evidence to draw any conclusions. Only one trial reported on live birth, clinical pregnancy or adverse effects in the antioxidant versus antioxidant comparison, and no conclusions could be drawn. Very low-quality evidence suggests that pentoxifylline may be associated with an increased clinical pregnancy rate compared with placebo or no treatment (OR 2.07, 95% CI 1.20 to 3.56, P = 0.009, 3 RCTs, 276 women, I2 = 0%). This suggests that among subfertile women with an expected clinical pregnancy rate of 25%, the rate among women using pentoxifylline would be between 28% and 53%. There was insufficient evidence to determine whether there was a difference between the groups in rates of miscarriage (OR 1.34, 95% CI 0.46 to 3.90, P = 0.58, 3 RCTs, 276 women, I2 = 0%) or multiple pregnancy (OR 0.78, 95% CI 0.20 to 3.09, one RCT, 112 women, very low quality evidence). This suggests that among subfertile women with an expected miscarriage rate of 4%, the rate among women using pentoxifylline would be between 2% and 15%. For multiple pregnancy, the data suggest that among subfertile women with an expected multiple pregnancy rate of 9%, the rate among women using pentoxifylline would be between 2% and 23%. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency. In this review, there was very low-quality evidence to show that taking an antioxidant may provide benefit for subfertile women, but insufficient evidence to draw any conclusions about adverse events. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women. | The review includes 50 randomised controlled trials that compare antioxidants with placebo or with no treatment/standard treatment, or with another antioxidant, in a total of 6510 women. Funding sources were reported by only 14 of the 50 included trials. Very low-quality evidence suggests that antioxidants may be associated with an increased live birth and clinical pregnancy rate. Based on these results, we would expect that out of 100 subfertile women not taking antioxidants, 20 would have a baby, compared with between 26 and 43 women per 100 who would have a baby if taking antioxidants. There was insufficient evidence to draw any conclusions about the adverse effects of miscarriage, multiple births or gastrointestinal effects. Very low-quality evidence suggests that pentoxifylline may also be associated with increased rates of clinical pregnancy, but there were only three trials in this analysis. In this case we would expect that out of 100 subfertile women not taking pentoxifylline, 25 would become pregnant, compared with between 28 and 53 women per 100 who would become pregnant if taking pentoxifylline to improve their chances of getting pregnant. There was also insufficient evidence to draw any conclusions about the adverse effects of pentoxifylline. Only one trial measured one antioxidant against another,so there was no evidence available to draw any conclusion from this comparison. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency. |
No RCTs meeting the selection criteria were identified. Since it is unlikely, for ethical and practical reasons that an RCT of SCUs will be conducted, a systematic review of non-RCTs using the same protocol and criteria was conducted. There were eight non-RCTs that fulfilled the criteria for inclusion. Only four studies had data which could be extracted for pooling in meta-analysis. Differences between comparator groups in these nonRCTs ? for example in severity of dementia - were not adequately adjusted for and were common in the trial which accounted for almost all of the positive outcomes of SCUs (Nobili, 2006) All of the results of the outcomes came only from single studies except for "physical restraint use" at 6 months, which included data from two studies. A small improvement in total Neuropsychiatric Inventory scores, favouring SCU was noted in one study at 6, 12 and 18 months. The use of physical restraints was less common in SCUs at 6 and 12 months (OR= 0.46 (95% CI 0.27 to 0.80), p=0.006; and OR=0.49 (0.27 to 0.88), p=0.02 respectively). Patients in SCUs were less depressed at 3 months than those in traditional nursing home (WMD -6.30 (-7.88 to -4.72) Cornell points, p<0.00001). There was only one observation that favoured the control group: a small but significant effect favouring traditional nursing home care was observed at 6 months in the mean number of psychotropic medications used (WMD 0.20, CI 0.00 to 0.40, z=1.96, P=0.05). There are no identified RCTs investigating the effects of SCUs on behavioural symptoms in dementia, and no strong evidence of benefit from the available non-RCTs. It is probably more important to implement best practice than to provide a specialized care environment. The routine collection of data on behaviour, restraint and psychotropic drug use across multiple nursing home settings offers the best modality for formal evaluation of the benefit or otherwise of SCUs. | No randomized controlled trials (RCTs) can be found comparing the effect of SCUs against traditional nursing units in managing agitated behaviours in people suffering from dementia. This review has examined the results of non-RCTs. The findings about the outcomes of this review arise just from one study except for the outcome of "physical restraint use" at 6 months, which includes data from two studies. Selection bias is a major problem in non-RCTs, and confounds the limited evidence that favoured SCU care with regard to a decrease in agitated behaviour and in the use of physical restraints. A convincing case for the benefits of SCU care cannot be made and further studies are necessary. |
Nine safety and efficacy trials, and two safety trials, with over 3000 participants were included. In semi-immune children, RTS,S vaccine reduced clinical episodes of malaria by 26% (95% CI 13% to 37%) and severe malaria by 58% (95% CI 15% to 79%) for up to 18 months. Prevalence of parasitaemia was also reduced by 26% (95% CI 11% to 38%) at six months after immunization. RTS,S also reduced clinical malaria episodes by 63% (95% CI 18% to 83%) in semi-immune adult men in the second year of follow up after a booster dose. No severe adverse events were judged to be related to RTS,S vaccine, although the frequencies of injection site pain, swelling, arm motion limitation, headache, and malaise were increased in the vaccine groups. There was no evidence for effect of the CS-NANP vaccines (307 participants, 3 trials), CS102 peptide vaccine (14 participants, 1 trial), or the ME-TRAP vaccine (372 participants, 1 trial). RTS,S vaccine was effective in preventing a significant number of clinical malaria episodes, including good protection against severe malaria in children for 18 months. No severe adverse events were attributable to the vaccine. Progression of this vaccine towards licensing is justified while efforts to increase its efficacy continue. The other vaccines do not look promising and further research is a priority. | This review looks at vaccines targeted at the 'pre-erythrocytic' phase of the parasite's life, the phase before the parasites first enter the bloodstream from the liver. Trials of four types of vaccine against P. falciparum, the most important human malaria species, were available for this review. One of these (the RTS,S vaccine) significantly reduced the number of episodes of clinical malaria and severe malaria in children, while the other three vaccines were not effective under the conditions of the trials. No severe adverse events observed following the RTS,S vaccination were judged to be related to vaccination, though minor adverse events like headache, swelling, and malaise were. |
We included data from 67,688 participants randomised into 13 RCTs. The included trials directly compared dose-adjusted warfarin with either apixaban, betrixaban, darexaban, edoxaban, idraparinux, idrabiotaparinux, or rivaroxaban. The majority of the included data (approximately 90%) was from apixaban, edoxaban, and rivaroxaban. The composite primary efficacy endpoint of all strokes (both ischaemic and haemorrhagic) and non-central nervous systemic embolic events was reported in all of the included studies. Treatment with a factor Xa inhibitor significantly decreased the number of strokes and systemic embolic events compared with dose-adjusted warfarin in participants with AF (OR 0.89, 95% CI 0.82 to 0.97; 13 studies; 67,477 participants; high-quality evidence). Treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.78, 95% CI 0.73 to 0.84; 13 studies; 67,396 participants; moderate-quality evidence). There was, however, statistically significant and high heterogeneity (I2 = 83%). When we repeated this analysis using a random-effects model, it did not show a statistically significant decrease in the number of major bleedings (OR 0.88, 95% CI 0.66 to 1.17). A pre-specified sensitivity analysis excluding all open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.75, 95% CI 0.69 to 0.81), but high heterogeneity was also observed in this analysis (I2 = 72%). The same sensitivity analysis using a random-effects model also showed a statistically significant decrease in the number of major bleedings in participants treated with factor Xa inhibitors (OR 0.76, 95% CI 0.60 to 0.96). Treatment with a factor Xa inhibitor significantly reduced the risk of intracranial haemorrhages (ICHs) compared with warfarin (OR 0.50, 95% CI 0.42 to 0.59; 12 studies; 66,259 participants; high-quality evidence). We observed moderate, but statistically significant heterogeneity (I2 = 55%). The pre-specified sensitivity analysis excluding open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of ICHs compared with warfarin (OR 0.47, 95% CI 0.40 to 0.56), with low, non-statistically significant heterogeneity (I2 = 27%). Treatment with a factor Xa inhibitor also significantly reduced the number of all-cause deaths compared with warfarin (OR 0.89, 95% 0.83 to 0.95; 10 studies; 65,624 participants; moderate-quality evidence). Treatment with factor Xa inhibitors significantly reduced the number of strokes and systemic embolic events compared with warfarin in people with AF. The absolute effect of factor Xa inhibitors compared with warfarin treatment was, however, rather small. Factor Xa inhibitors also reduced the number of ICHs, all-cause deaths and major bleedings compared with warfarin, although the evidence for a reduction in the latter is less robust. | We searched various sources up to 29 August 2017 and included 13 studies that involved 67,688 people with atrial fibrillation who received either a factor Xa inhibitor or a vitamin K antagonist. All included people were adults and on average aged between 65 and 74 years. Approximately one-third were women. We found that factor Xa inhibitors when compared with warfarin, which was used as comparator in all trials, reduced the number of strokes in people with atrial fibrillation. This reduction was, however, rather small. Factor Xa inhibitors also appeared to reduce the number of serious bleedings (including those into the brain) and the number of people dying from any cause compared with warfarin. We considered the quality of evidence in our review as moderate to high. The studies that we included were generally large to very large. We found that the results from the larger studies were generally similar and this strengthened our findings. Finally, we are confident that we included all relevant studies in our review and did not miss any important studies. |
Only one study evaluating lamotrigine in secondary progressive MS was eligible. One hundred and twenty people were included, 61 randomly assigned to lamotrigine treatment and 59 to placebo treatment. The average age of participants in the two groups was 51.9 years and 50.1 years, respectively. The proportion of male participants was 27.5%. The period of follow-up was 2 years. No data were found on disability progression and people who experienced relapses. No significant differences were found for serious adverse events between the two groups. Treatment with lamotrigine was associated with more rashes (20% vs 5%, P value 0.03) and transient, dose-related deterioration of mobility (66% vs 34%, P value 0.001) than placebo. Furthermore, no significant difference between the two groups was found in the magnetic resonance imaging (MRI) measurements of cerebral atrophy, Expanded Disability Status Score changes, Multiple Sclerosis Functional Composite score changes. This study was judged to be at high risk of bias. This review will be updated when the three ongoing studies we identified are completed. The quality of evidence was judged to be very low due to the low number of available studies and included participants. There is a lack of evidence to address the review question on the efficacy of sodium channel blockers for people with MS. Assessment of the three ongoing trials might change this conclusion. Further high-quality large scale studies are needed. | We searched for randomised controlled trials (RCTs), in which participants were randomly assigned to a treatment group or a control group. In most settings these studies provide the highest quality evidence. We were interested in studies that compared a sodium channel blocker with placebo, or used it as an add-on to any approved treatments for MS. We found only one study including a total of 120 participants. No data were found on disability progression and people who experienced relapses. No significant difference between two groups was found in measurements of cerebral atrophy, expanded disability score changes, or MS functional composite score changes. Treatment with lamotrigine was associated with more rashes (20% versus 5%) and transient, dose-related deterioration of mobility. There is a lack of evidence to address the review question on the efficacy of sodium channel blockers for people with MS. This review will be updated when the three ongoing studies we identified are completed. The quality of evidence was judged as very low due to the low number of available studies and included population. There is a lack of evidence to address the review question on the efficacy of sodium channel blockers for people with MS. Assessment of the three ongoing trials might change this conclusion. Further high-quality large-scale studies are needed. |
The review included 27 studies reported in 30 articles. The studies had 73,557 participants with 12 studies from the US; four from China; two from each of Australia, Canada, the Netherlands and the UK; and one from each of Israel, Greece and Brazil. Thirteen studies were RCTs, six were non-RCTs and eight were CBAs. Of the included studies, 18 provided some element of the intervention in children aged four to 11 years, 17 studies included children aged 11 to 14 years and nine studies included children aged 14 to 18 years. The overall quality of the results was poor, with the all studies assessed as being at high or unclear risks of bias across multiple domains, and varied interventions and data collection methods employed. Interventions comprised information-giving, peer education or were multi-component. Seven studies reported the primary outcome of injury occurrence and only three of these were similar enough to combine in a meta-analysis, with a pooled incidence rate ratio of 0.73 (95% confidence interval (CI) 0.49 to 1.08; 2073 children) and substantial statistical heterogeneity (I2 = 63%). However, this body of evidence was low certainty, due to concerns over this heterogeneity (inconsistency) and imprecision. This heterogeneity may be explained by the non-RCT study design of one of the studies, as a sensitivity analysis with this study removed found stronger evidence of an effect and no heterogeneity (I2 = 0%). Two studies report an improvement in safety skills in the intervention group. Likewise, the four studies measuring observed safety behaviour reported an improvement in the intervention group relative to the control. Thirteen out of 19 studies describing self-reported behaviour and safety practices showed improvements, and of the 21 studies assessing changes in safety knowledge, 19 reported an improvement in at least one question domain in the intervention compared to the control group. However, we were unable to pool data for our secondary outcomes, so our conclusions were limited, as they were drawn from highly diverse single studies and the body of evidence was low (safety skills) or very low (behaviour, safety knowledge) certainty. Only one study reported intervention costs but did not undertake a full economic evaluation (very low certainty evidence). There is insufficient evidence to determine whether school-based educational programmes can prevent unintentional injuries. More high-quality studies are needed to evaluate the impact of educational programmes on injury occurrence. There is some weak evidence that such programmes improve safety skills, behaviour/practices and knowledge, although the evidence was of low or very low quality certainty. We found insufficient economic studies to assess cost-effectiveness. | The evidence is current to June 2015. It includes the results from 27 studies of 73,557 children. It included boys and girls aged four to 18. The studies compared injury prevention education with either the usual curriculum or an alternative programme unrelated to injuries. The studies we included were aimed at preventing a range of injuries. We excluded programmes that focused on just one cause of injury. The review measured the effects of the educational programmes on the occurrence of injuries in children, their safety skills, behaviour and knowledge. The review also looked at whether school-based approaches are good value for money. Only a few studies reported the effect on injury occurrence in children and so these effects were inconclusive. This does not mean that school-based programmes are ineffective but rather that more evidence is needed. The review did find evidence that school-based injury prevention education programmes can improve children's safety skills, safety behaviours and safety knowledge. However, the evidence was inconsistent, with some studies showing a positive effect and others showing no effect. Only one study reported on how cost-effective school-based programmes were and so again it is difficult to draw conclusions from this evidence alone. The studies were generally of poor quality for all the measurements of effectiveness of the programmes but particularly for behaviour and knowledge. This is because information about how the study was conducted was not usually reported very clearly in the study reports or there were major flaws in the way that the studies were undertaken. More research is needed that is of higher quality. |
We included 35 RCTs analysing 3102 participants. Thirteen studies were at low risk of bias, 12 studies were at unclear risk of bias, and 10 studies were at high risk of bias. Our main findings were regarding keratinocyte growth factor (KGF) and are summarised as follows. There might be a reduction in the risk of moderate to severe oral mucositis in adults receiving bone marrow/stem cell transplantation after conditioning therapy for haematological cancers (RR 0.89, 95% CI 0.80 to 0.99; 6 studies; 852 participants; low-quality evidence). We would need to treat 11 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 6 to 112). There might be a reduction in the risk of severe oral mucositis in this population, but there is also some possibility of an increase in risk (RR 0.85, 95% CI 0.65 to 1.11; 6 studies; 852 participants; low-quality evidence). We would need to treat 10 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 5 to prevent the outcome to 14 to cause the outcome). There is probably a reduction in the risk of moderate to severe oral mucositis in adults receiving radiotherapy to the head and neck with cisplatin or fluorouracil (RR 0.91, 95% CI 0.83 to 1.00; 3 studies; 471 participants; moderate-quality evidence). We would need to treat 12 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 7 to infinity). It is very likely that there is a reduction in the risk of severe oral mucositis in this population (RR 0.79, 95% CI 0.69 to 0.90; 3 studies; 471 participants; high-quality evidence). We would need to treat 7 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 5 to 15). It is likely that there is a reduction in the risk of moderate to severe oral mucositis in adults receiving chemotherapy alone for mixed solid and haematological cancers (RR 0.56, 95% CI 0.45 to 0.70; 4 studies; 344 participants; moderate-quality evidence). We would need to treat 4 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 3 to 6). There might be a reduction in the risk of severe oral mucositis in this population (RR 0.30, 95% CI 0.14 to 0.65; 3 studies; 263 participants; low -quality evidence). We would need to treat 10 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 8 to 19). Due to the low volume of evidence, single-study comparisons and insufficient sample sizes, we found no compelling evidence of a benefit for any other cytokines or growth factors and there was no evidence on children. There did not appear to be any serious adverse effects of any of the interventions assessed in this review. We are confident that KGF is beneficial in the prevention of oral mucositis in adults who are receiving: a) radiotherapy to the head and neck with cisplatin or fluorouracil; or b) chemotherapy alone for mixed solid and haematological cancers. We are less confident about a benefit for KGF in adults receiving bone marrow/stem cell transplant after conditioning therapy for haematological cancers because of multiple factors involved in that population, such as whether or not they received total body irradiation (TBI) and whether the transplant was autologous (the patients' own cells) or allogeneic (cells from a donor). KGF appears to be a relatively safe intervention. Due to limited research, we are not confident that there are any beneficial effects of other cytokines and growth factors. There is currently insufficient evidence to draw any conclusions about the use of cytokines and growth factors in children. | Authors from Cochrane Oral Health carried out this review of existing studies and the evidence is current up to 10 May 2017. It includes 35 studies (published between 1993 and 2017) with 3102 participants, all patients being treated for cancer, aged from 1 to 87 years old. Review authors included studies comparing cytokines and growth factors for the prevention of oral mucositis. The studies were carried out all over the world and often featured multiple sites, although most took place in high-income countries. The main findings were regarding keratinocyte growth factor (KGF). KGF is likely to reduce the risk of oral mucositis in adults who are receiving either radiotherapy to the head and neck with chemotherapy (cisplatin or fluorouracil), or chemotherapy alone for mixed solid and blood cancers. KGF may also reduce the risk of oral mucositis in adults receiving bone marrow/stem cell transplant after conditioning therapy for blood cancers, but these results are less clear because of multiple complicating factors. KGF appears to be a relatively safe intervention. There did not appear to be any serious adverse effects of any of the interventions assessed in this review. Due to limited research, review authors are uncertain of any beneficial effects of other cytokines and growth factors. There is currently insufficient evidence to draw any conclusions about the use of cytokines and growth factors in children. For reducing oral mucositis in adults receiving radiotherapy to the head and neck with chemotherapy, review authors rated the evidence for KGF as moderate to high quality. For reducing oral mucositis in adults receiving chemotherapy alone for mixed solid and blood cancers, they rated the evidence for KGF as low to moderate quality. This evidence was downgraded due to there not being enough data and because some results have not yet been published. For reducing oral mucositis in adults receiving bone marrow/stem cell transplant after conditioning therapy for blood cancers, they rated the evidence for KGF as low quality because results were not similar across the studies and some results have not yet been published. Evidence on side effects of KGF was poorly reported and inconsistent. |
We included seven RCTs and five CBA studies. Six studies evaluated the effectiveness of educational materials alone, one study evaluated educational meetings, four studies evaluated a combination of the two, and one study evaluated a multifaceted educational campaign for increasing the reporting of occupational diseases by physicians. We judged all the included studies to have a high risk of bias. We did not find any studies evaluating the effectiveness of Internet-based interventions or interventions on procedures or techniques of reporting, or the use of financial incentives. Moreover, we did not find any studies evaluating large-scale interventions like the introduction of new laws, existing or new specific disease registries, newly established occupational health services, or surveillance systems. Educational materials We found moderate-quality evidence that the use of educational materials did not considerably increase the number of physicians reporting occupational diseases compared to no intervention (risk ratio of 1.11, 95% confidence interval (CI) 0.74 to 1.67). We also found moderate-quality evidence showing that sending a reminder message of a legal obligation to report increased the number of physicians reporting occupational diseases (risk ratio of 1.32, 95% CI 1.05 to 1.66) when compared to a reminder message about the benefits of reporting. We found low-quality evidence that the use of educational materials did not considerably increase the rate of reporting when compared to no intervention. Educational materials plus meetings We found moderate-quality evidence that the use of educational materials combined with meetings did not considerably increase the number of physicians reporting when compared to no intervention (risk ratio of 1.22, 95% CI 0.83 to 1.81). We found low-quality evidence that educational materials plus meetings did not considerably increase the rate of reporting when compared to no intervention (rate ratio of 0.77, 95% CI 0.42 to 1.41). Educational meetings We found very low-quality evidence showing that educational meetings increased the number of physicians reporting occupational diseases (risk ratio at baseline: 0.82, 95% CI 0.47 to 1.41 and at follow-up: 1.74, 95% CI 1.11 to 2.74) when compared to no intervention. We found very low-quality evidence that educational meetings did not considerably increase the rate of reporting occupational diseases when compared to no intervention (rate ratio at baseline: 1.57, 95% CI 1.22 to 2.02 and at follow-up: 1.92, 95% CI 1.48 to 2.47). Educational campaign We found very low-quality evidence showing that the use of an educational campaign increased the number of physicians reporting occupational diseases when compared to no intervention (risk ratio at baseline: 0.53, 95% CI 0.19 to 1.50 and at follow-up: 11.59, 95% CI 5.97 to 22.49). We found 12 studies to include in this review. They provide evidence ranging from very low to moderate quality showing that educational materials, educational meetings, or a combination of the two do not considerably increase the reporting of occupational diseases. The use of a reminder message on the legal obligation to report might provide some positive results. We need high-quality RCTs to corroborate these findings. Future studies should investigate the effects of large-scale interventions like legislation, existing or new disease-specific registries, newly established occupational health services, or surveillance systems. When randomisation or the identification of a control group is impractical, these large-scale interventions should be evaluated using an interrupted time-series design. We also need studies assessing online reporting and interventions aimed at simplifying procedures or techniques of reporting and the use of financial incentives. | We included 12 studies. Six studies evaluated the effectiveness of educational materials alone; one study evaluated the effectiveness of educational meetings; and four studies evaluated a combination of the two in increasing the reporting of occupational diseases by physicians. A further study evaluated the effectiveness of a complex educational campaign acting at society level. We searched for studies until January 2015. We found that the use of educational materials did not considerably increase the number of physicians reporting occupational diseases, but a legal obligation reminder message did. Furthermore, we found that the use of educational materials did not considerably increase the rate of reporting occupational diseases. Similarly, we found that the use of both educational materials and meetings did not considerably increase the number of physicians reporting occupational diseases or the rate of reporting. The same holds for the use of educational meetings alone. The use of an educational campaign appeared to increase the number of physicians reporting occupational diseases, although this was based on very low-quality evidence. We need high-quality studies to clarify the effectiveness of these interventions. This review was unable to determine the effectiveness of interventions other than education like the use of financial incentives, which could be an important form of motivation in changing physicians' behaviour. Such small-scale interventions could be investigated using larger randomised controlled trials, while the evaluation of large-scale interventions like legislation should use an interrupted time-series design. |
We included one randomised trial of 55 children aged between 16 months to 15 years. It compared anatomically-guided FICB versus systemic analgesia with intravenous morphine sulphate. The small sample size and the high risk of bias relating to lack of blinding resulted in a low quality rating for all outcomes. Overall, the trial provided low quality evidence for better pain management in the FICB group. Fewer children in the FICB group had analgesia failure at 30 minutes than in the morphine group (2/26 (8%) versus 8/28 (29%); risk ratio (RR) 0.33, 95% confidence interval (CI) 0.09 to 1.20; P value 0.09). The trial did not report on pain during procedures or transfers, or application of analgesia. The trial provided low quality evidence that FICB has a better safety profile than morphine, with only four (15%) reports of redness and pain at the injection site, and no reports of the type of adverse effects of systematic analgesia that occurred in the morphine group, such as respiratory depression (six cases (21%)) and vomiting (four cases (14%)). No long-term adverse events were reported for either intervention. Clinically significant pain relief was achieved in both groups at five minutes; with limited evidence of greater initial pain relief in the FICB group. Based on an inspection of graphically-presented data, at least 46% (12/26) of children in the FICB group had no supplementary medication (mainly analgesia) for the six hours of the study, while only 5% (1 or 2/28) of children in the intravenous morphine group went without additional analgesia. There was insufficient evidence to determine whether child or parental satisfaction with the method of analgesia favoured either method. Resource use was not measured. Low quality evidence from one small trial suggests that FICB provides better and longer lasting pain relief with fewer adverse events than intravenous opioids for femur fractures in children. Well conducted and reported randomised trials that compare nerve blocks (both FNB and FICB) with systemic analgesia and that use validated pain scores are needed. | We searched several medical databases and trial registries up to January 2013 and contacted researchers. We found one study that looked at the comparison we were interested in. This study was potentially biased, mainly because the care providers, parents and children were aware of the type of pain relief the children received. The study was small, involving 55 children aged 16 months to 15 years, and showed that the children who received one of the two main types of nerve block tended to have less pain after 30 minutes than those who received intravenous morphine for initial pain control. The nerve blocks led to some pain and redness at the injection site in a few cases, while intravenous morphine caused more serious problems such as depressed breathing (lack of oxygen), excessive sleepiness and vomiting in a small number of children. Moreover, children who had nerve blocks continued to have lower pain scores over a six-hour period with less need for additional pain relief. There was insufficient evidence to determine whether children or parents were more satisfied with one method of pain relief than the other. Use of resources (e.g. nursing time, cost of medications) was not measured. The quality of the study included in this review was low and so these conclusions are not certain. Further well designed studies investigating whether nerve blocks are more effective and safer than other means of pain relief are needed. |
We included 26 trials with 2084 participants analysed. Most of the studies were conducted in the United Kingdom (UK) and United States (US), and involved men and women experiencing their first episode of genital herpes, with the exception of three studies which included only women. We rated the majority of these studies as having an unclear risk of bias; largely due to lack of information supplied in the publications, and due to the age of the trials. This review found low quality evidence from two studies of oral acyclovir, when compared to placebo, reduced the duration of symptoms in individuals undergoing their first episode of genital herpes (mean difference (MD) -3.22, 95% confidence interval (CI) -5.91 to -0.54; I2 = 52%). In two studies (112 participants), intravenous acyclovir decreased the median number of days that patients with first-episode herpes suffered symptoms. Oral valaciclovir (converted to acyclovir) also showed a similar length of symptom duration when compared to acyclovir in two studies. There is currently no evidence that topical acyclovir reduces symptoms (MD -0.61 days, 95% CI -2.16 to 0.95; 3 RCTs, 195 participants, I2 statistic = 56%). There is also no current evidence that the topical treatments of cicloxolone cream, carbenoxolone sodium cream, adenosine arabinoside, idoxuridine in dimethyl sulfoxide, when compared to placebo reduced the duration of symptoms in people undergoing their first episode of herpes. Two studies reported no evidence of a reduction in the number of median days to recurrence following treatment with oral acyclovir versus placebo. Adverse events were generally poorly reported by all of the included studies and we were unable to quantitatively analyse this outcome. For those taking acyclovir, there were no serious adverse events; the most common adverse events reported for oral acyclovir were coryza, dizziness, tiredness, diarrhoea and renal colic. For intravenous acyclovir these were phlebitis, nausea and abnormal liver function tests and for topical acyclovir there was pain with the topical application.Those undergoing interferon treatment had significantly more adverse events compared to those taking placebo. There is low quality evidence from this review that oral acyclovir reduced the duration of symptoms for genital herpes. However, there is low quality evidence which did not show that topical antivirals reduced symptom duration for patients undergoing their first episode of genital herpes. This review was limited by the inclusion of skewed data, resulting in few trials that we were able to meta-analyse. | We included 26 randomised controlled trials (RCTs) trials with 2084 participants that looked at treatments for first-episode genital herpes versus placebo or another treatment. The trials all included people who were having their first episode of genital herpes and were conducted in various countries around the world. Three of the trials included only women, and in all the trials the participants had had symptoms for eight days or less. Fifteen of the 26 trials were funded by a pharmaceutical company.Key resultsThe evidence is current to April 2016. The evidence shows that oral and intravenous acyclovir may be effective in reducing the number of days of symptoms in someone with first-episode genital herpes. Oral valaciclovir showed a similar length of symptom duration as acyclovir. We did not find enough evidence to support the use of topical treatments. There was also no evidence that any of the treatments reduced the time between episodes for people with genital herpes. The evidence presented here is mostly of low quality. The studies included were mainly conducted in the 1980s and at this time the brief way studies were reported does not allow us to adequately judge the quality of the included studies.Quality of the evidenceThe evidence provided by this review is of low quality. Although there are 26 included studies, the meta-analyses created in this review at the most, had three included studies. This was mainly due to the low number of studies that looked at each different type of antiviral. It was also unclear as to how well the included studies were conducted, as the methods for each of the individual studies did not report enough detail to judge each study's quality, inconsistence and this also affected the overall quality of the review. |
We included nine randomised trials, published between 1998 and 2014, involving 662 participants. The population consisted of both children and adolescents in four trials, only adults in four trials, and both children/adolescents and adults in one trial. Four studies examined only permanent teeth, and five studies evaluated both deciduous and permanent teeth. Six trials used Er:YAG (erbium-doped yttrium aluminium garnet) lasers, two trials employed Er,Cr:YSGG (erbium, chromium: yttrium-scandium-gallium-garnet) lasers, and one trial used Nd:YAG (neodymium-doped yttrium aluminium garnet) laser. Overall, the trials had small sample sizes, and the majority were at unclear or high risk of bias. The primary outcomes were evaluated in a limited number of trials (removal of caries (four trials (but only two reported quantitative data)); episodes of pain (five studies)). There was insufficient evidence to suggest that either lasers or drill were better at caries removal (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.99 to 1.01; 2 studies; 256 treated caries; P = 0.75; I2 = 0%; low-quality evidence). The incidence of moderate or high pain was greater in the drill group compared to the laser group (RR 0.40, 95% CI 0.28 to 0.57; 2 studies; 143 participants; P < 0.001; I2 = 50%). Similarly, the need for anaesthesia was significantly higher in the drill group than in the laser group (RR 0.25, 95% CI 0.10 to 0.65; 3 studies; 217 children/adolescents; P = 0.004; I2 = 0%). In terms of marginal integrity of restoration, there was no evidence of a difference between laser and drill comparisons evaluated at 6 months (RR 1.00, 95% CI 0.21 to 4.78; 3 studies), 1 year (RR 1.59, 95% CI 0.34 to 7.38; 2 studies), or 2 years (RR 1.00, 95% CI 0.21 to 4.74; 1 study). There was no evidence of a difference for durability of restoration between laser therapy or drill at 6 months' follow-up (RR 2.40, 95% CI 0.65 to 8.77; 4 studies), at 1 year (RR 1.40, 95% CI 0.29 to 6.78; 2 studies) or at 2 years' follow-up (RR 0.50, 95% CI 0.02 to 14.60; 1 study). Only two trials investigated the recurrence of caries, but no events occurred during 6 months' follow-up. There was insufficient evidence of a difference between laser or drill in terms of pulpal inflammation or necrosis at 1 week (RR 1.51, 95% CI 0.26 to 8.75; 3 studies) and at 6 months (RR 0.99, 95% CI 0.10 to 9.41; 2 studies). Given the low quality of the body of evidence, we concluded that evidence was insufficient to support the use of laser as an alternative to traditional drill therapy for caries removal. We found some evidence in favour of laser therapy for pain control, need of anaesthesia and patient discomfort, but, again, the body of evidence was of low quality. Additional well-designed, randomised trials investigating the most relevant outcomes are needed. | Cochrane Oral Health provided the search strategies and carried out the search in several electronic databases. We selected nine randomised trials for inclusion in this review that were conducted between 1998 and 2014. The evidence in the review is up to date as of 22 June 2016. The trials involved a total of 662 participants, with 1498 teeth treated. Three studies were conducted in the USA, one in Taiwan, one in China, one in Bulgaria, one in Germany, one in Turkey and one in the UK. The population consisted of both children and adolescents in four trials, only adults in four trials, and both children/adolescents and adults in one trial. Despite the number of included studies, only a few trials adequately and completely reported information on the primary outcomes. Two trials reported on removal of decay, and there was not enough evidence to conclude that either lasers or drills were better at decay removal. Only five trials reported on episodes of pain, which was significantly reduced in people treated with lasers. There was no difference in terms of side effects, such as inflammation or death of dental pulp, between the two interventions. The overall quality of the evidence for the nine studies was low. Only one study adequately randomised participants, and none of the included studies was at low risk of bias. This review highlights the need for high-quality studies comparing laser therapy and mechanical drills in the treatment of dental decay. |
Three randomised controlled trials (340 patients) and 12 non-randomised studies (4081 patients) were included. There was significant statistical heterogeneity in the analysis of many of the outcomes. We found no significant difference between care pathway and control groups in terms of death or discharge destination. Patients managed with a care pathway were: (1) more dependent at discharge (P = 0.04); (2) less likely to suffer a urinary tract infection (Odds Ratio (OR) 0.51, 95% Confidence Interval (CI) 0.34 to 0.79); (3) less likely to be readmitted (OR 0.11, 95% CI 0.03 to 0.39); and (4) more likely to have neuroimaging (OR 2.42, 95% CI 1.12 to 5.25). Evidence from randomised trials suggested that patient satisfaction and quality of life were significantly lower in the care pathway group (P = 0.02 and P < 0.005 respectively). Use of stroke care pathways may be associated with positive and negative effects. Since most of the results have been derived from non-randomised studies, they are likely to be influenced by potential biases and confounding factors. There is currently insufficient supporting evidence to justify the routine implementation of care pathways for acute stroke management or stroke rehabilitation. | The review found that patients treated within a care pathway may be less likely to suffer some complications (e.g. urine infections), and more likely to have certain tests (e.g. brain scans). However, the use of care pathways may also reduce the patient's likelihood of functioning independently when discharged from hospital, their quality of life, and their satisfaction with hospital care. Currently, there is not enough evidence to justify introducing care pathways for the routine care of all patients with stroke. Further research is needed to find out if care pathways for stroke do more good than harm. |
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