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cochrane-simplification-train-1000

cochrane-simplification-train-1000

This review included six randomised controlled trials that enrolled a total of 564 adults undergoing elective midline laparotomy for colorectal resection comparing continuous wound infusion of a local anaesthetic to a normal saline placebo. Due to 23 post-randomisation exclusions, a total of 541 participants contributed data to the analysis of at least one outcome (local anaesthetic 268; control 273). Most participants were aged 55 to 65 years, with normal body mass index and low to moderate anaesthetic risk (American Society of Anesthesiologists class I-III). Random sequence generation, allocation concealment, and blinding were appropriately carried out in most trials. However, we had to downgrade the certainty of the evidence for most outcomes due to serious study limitations (risk of bias), inconsistency, indirectness, imprecision and reporting bias. Primary outcomes On postoperative day 1, pain at rest (mean difference (MD) −0.59 (from 3.1), 95% confidence interval (CI) −1.12 to −0.07; 5 studies, 511 participants; high-certainty evidence), pain on movement (MD −1.1 (from 6.1), 95% CI −2.3 to −0.01; 3 studies, 407 participants; low-certainty evidence) and opioid consumption via PCA (MD −12 mg (from 41 mg), 95% CI −20 to −4; 6 studies, 528 participants; moderate-certainty evidence) were reduced in the local anaesthetic group compared to the control group. Secondary outcomes There was a reduction in the time to first bowel movement (MD −0.67 from 4.4 days, 95% CI −1.17 to −0.17; 4 studies, 197 participants; moderate-certainty evidence) and the length of hospital stay (MD −1.2 from 7.4 days, 95% CI −2.0 to −0.3; 4 studies, 456 participants; high-certainty evidence) in the local anaesthetic group compared to the control group. There was no evidence of a difference in any serious postoperative adverse events until hospital discharge (RR 1.04, 95% CI 0.68 to 1.58; 6 studies, 541 participants; low-certainty evidence) between the two study groups. After elective midline laparotomy for colorectal resection, continuous wound infusion of a local anaesthetic compared to a normal saline placebo reduces postoperative pain at rest and the length of hospital stay, on the basis of high-certainty evidence. This means we are very confident that the effect estimates for these outcomes lie close to the true effects. There is moderate-certainty evidence to indicate that the intervention probably reduces opioid consumption via PCA and the time to first bowel movement. This means we are moderately confident that effect estimates for these outcomes are likely to be close to the true effects, but there is a possibility that they are substantially different. The intervention may reduce postoperative pain on movement, however, this conclusion is based on low-certainty evidence. This means our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect. There is low-certainty evidence to indicate that the intervention may have little or no effect on the rates of any serious postoperative adverse events until hospital discharge. High-quality randomised controlled trials to evaluate the intervention with a focus on important clinical and patient-centred outcomes are needed.

We searched for clinical trials to January 2019 looking at the benefits and harms of continuous injection of a local anaesthetic after surgery to remove the bowel through a vertical cut in the abdomen. We looked for trials comparing local anaesthetic to an inactive substance (placebo) such as salty water (normal saline). We found six clinical trials including 541 participants. Most participants were aged 55 to 65 years, of varying health status from fit and healthy to having a severe systemic disease (a disease that affects the whole body). In people who received a local anaesthetic, pain at rest, pain on movement, and requirement for morphine-like pain killers were reduced on the first day after surgery compared to people who received an inactive substance. People who received a local anaesthetic also opened their bowels about half a day earlier and were discharged from hospital about a day earlier compared to people who received an inactive substance. We did not find a difference between people who received a local anaesthetic and those who received an inactive substance in the rates of any serious complications after surgery until hospital discharge. We rated the certainty of the evidence from studies using four levels: high, moderate, low, very low. Reasons for downgrading the certainty of the evidence included limitations problems with the design of the studies, missing data, differences between trials and how the outcomes were measured, and the small number of participants. We need more high-quality trials to evaluate this treatment, especially its effects on recovery after surgery, side effects and complications. We rated the certainty of the evidence for pain after surgery at rest and the length of hospital stay as high, meaning that we are very confident in the findings about the effects of the treatment on these outcomes. We rated the certainty of the evidence for the requirement for morphine-like pain killers and the time until the first bowel movement as moderate. This means that we are moderately confident in the findings about the effects of the treatment on these outcomes. We rated the certainty of the evidence for pain after surgery on movement and the rates of any serious complications after surgery until hospital discharge as low, meaning that we have limited confidence in the findings about the effects of the treatment on these outcomes.

10.1002/14651858.CD012310.pub2

cochrane-simplification-train-1001

cochrane-simplification-train-1001

Ten new studies were identified so a total of 34 studies (3033 total participants) were included in the 2015 review update. The risk of bias attributes were frequently poorly performed. Low risk of bias was reported in 18 studies for sequence generation, 16 studies for allocation concealment, seven for performance and detection bias, 15 for incomplete reporting and 16 for selective reporting. Three months or more of prednisone significantly reduced the risk of frequently relapsing nephrotic syndrome (FRNS) (6 studies, 582 children: RR 0.68, 95% CI 0.47 to 1.00) and of relapse by 12 to 24 months (8 studies, 741 children: RR 0.80, 95% CI 0.64 to 1.00) compared with two months. Five or six months of prednisone significantly reduced the risk of relapse (7 studies, 763 children: RR 0.62, 95% CI 0.45 to 0.85) but not FRNS (5 studies, 591 children: RR 0.78, 95% CI 0.50 to 1.22) compared with three months. However there was significant heterogeneity in the analyses. Subgroup analysis stratified by risk of bias for allocation concealment showed that the risk for FRNS did not differ significantly between two or three months of prednisone and three to six months among studies at low risk of bias but was significantly reduced in extended duration studies compared with two or three months in studies at high risk or unclear risk of bias. There were no significant differences in the risk of adverse effects between extended duration and two or three months of prednisone. Four studies found that in children with FRNS, daily prednisone during viral infections compared with alternate-day prednisone or no treatment significantly reduced the rate of relapse. In this 2015 update the addition of three well-designed studies has changed the conclusion of this review. Studies of long versus shorter duration of corticosteroids have heterogeneous treatment effects, with the older high risk of bias studies tending to over-estimate the effect of longer course therapy, compared with more recently published low risk of bias studies. Among studies at low risk of bias, there was no significant difference in the risk for FRNS between prednisone given for two or three months and longer durations or total dose of therapy indicating that there is no benefit of increasing the duration of prednisone beyond two or three months in the initial episode of SSNS. The risk of relapse in children with FRNS is reduced by the administration of daily prednisone at onset of an upper respiratory tract or viral infection. Three additional studies have increased the evidence supporting this conclusion. This management strategy may be considered for children with FRNS. A paucity of data on prednisone use in relapsing nephrotic syndrome remains. In particular there are no data from RCTs evaluating the efficacy and safety of prolonged courses of low dose alternate-day prednisone although this management strategy is recommended in current guidelines.

We looked at evidence from 34 studies enrolling 3033 children. Fourteen of 21 studies, in children with their first episode of nephrotic syndrome, evaluated prednisone for two or three months compared with longer durations. Thirteen studies evaluated different corticosteroid regimens in children with frequently relapsing disease (FRNS). Studies were of variable methodological quality with only about half of the studies at low risk of bias. Among studies of long versus shorter duration of prednisone, older studies at high or unclear risk of bias tended to over-estimate the effect of longer course therapy compared with new studies at low risk of bias. Studies at low risk of bias found no significant differences in the risk of relapse or the development of FRNS between prednisone given for three to six months compared with two or three months. Therefore there is no benefit of increasing the duration of prednisone beyond two or three months in the initial episode of SSNS. Based on four studies in children with frequently relapsing nephrotic syndrome, prednisone given for five to seven days at the onset of a viral infection reduces the risk of relapse. This review updates information previously published in 2000, 2003, 2005 and 2007. The addition of three new studies evaluating different durations of prednisone in the first episode of nephrotic syndrome has changed the conclusions expressed in previous versions of this review

10.1002/14651858.CD001533.pub5

cochrane-simplification-train-1002

cochrane-simplification-train-1002

Eleven trials including 5662 participants met the inclusion criteria. DOT was performed by a range of people (nurses, community health workers, family members or former TB patients) in a variety of settings (clinic, the patient's home or the home of a community volunteer). DOT versus self-administered Six trials from South Africa, Thailand, Taiwan, Pakistan and Australia compared DOT with self-administered therapy for treatment. Trials included DOT at home by family members, community health workers (who were usually supervised); DOT at home by health staff; and DOT at health facilities. TB cure was low with self-administration across all studies (range 41% to 67%), and direct observation did not substantially improve this (RR 1.08, 95% CI 0.91 to 1.27; five trials, 1645 participants, moderate quality evidence). In a subgroup analysis stratified by the frequency of contact between health services in the self-treatment arm, daily DOT may improve TB cure when compared to self-administered treatment where patients in the self-administered group only visited the clinic every month (RR 1.15, 95% CI 1.06 to 1.25; two trials, 900 participants); but with contact in the control becoming more frequent, this small effect was not apparent (every two weeks: RR 0.96, 95% CI 0.83 to 1.12; one trial, 497 participants; every week: RR 0.90, 95% CI 0.68 to 1.21; two trials, 248 participants). Treatment completion showed a similar pattern, ranging from 59% to 78% in the self-treatment groups, and direct observation did not improve this (RR 1.07, 95% CI 0.96 to 1.19; six trials, 1839 participants, moderate quality evidence). DOT at home versus DOT at health facility In four trials that compared DOT at home by family members, or community health workers, with DOT by health workers at a health facility there was little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.88 to 1.18, four trials, 1556 participants, moderate quality evidence; treatment completion: RR 1.04, 95% CI 0.91 to 1.17, three trials, 1029 participants, moderate quality evidence). DOT by family member versus DOT by community health worker Two trials compared DOT at home by family members with DOT at home by community health workers. There was also little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.86 to 1.21; two trials, 1493 participants, moderate quality evidence; completion: RR 1.05, 95% CI 0.90 to 1.22; two trials, 1493 participants, low quality evidence). Specific patient categories A trial of 300 intravenous drug users in the USA evaluated direct observation with no observation in TB prophylaxis to prevent active disease and showed little difference in treatment completion (RR 1.00, 95% CI 0.88 to 1.13; one trial, 300 participants, low quality evidence). From the existing trials, DOT did not provide a solution to poor adherence in TB treatment. Given the large resource and cost implications of DOT, policy makers might want to reconsider strategies that depend on direct observation. Other options might take into account financial and logistical barriers to care; approaches that motivate patients and staff; and defaulter follow-up.

This Cochrane Review summarises trials evaluating the effects of directly observed therapy (DOT) for treating people with tuberculosis (TB) or people on prophylaxis to prevent active disease compared to self-administered treatment. After searching for relevant trials up to 13 January 2015, we included 11 randomized controlled trials, enrolling 5662 people with TB, and conducted between 1995 and 2008. What is DOT and how might it improve treatment outcomes for people with TB DOT is one strategy to ensure that patients with TB take all their medication. An 'observer' acceptable to the patient and the health system observes the patient taking every dose of their medication, and records this for the health system to monitor. The World Health Organization currently recommends that people with TB are treated for at least six months to achieve cure. These long durations of treatment can be difficult for patients to complete, especially once they are well and need to return to work. Failure to complete treatment can lead to relapse and even death in individuals, and also has important public health consequences, such as increased TB transmission and the development of drug resistance. What the research says Overall, cure and treatment completion in both self-treatment and DOT groups was low, and DOT did not substantially improve this. Small effects were seen in a subgroup of studies where the self-treatment group were monitored less frequently than the DOT group. There is probably no difference in TB cure or treatment completion when the direct observation was conducted at home or at the clinic (moderate quality evidence). There is probably little or no difference in TB cure direct observation is conducted by a community health worker or family member (moderate quality evidence) and there may be little or no difference in treatment completion either (low quality evidence). Direct observation may have little or no effect on treatment completion in injection drug users (low quality evidence). The authors conclude that DOT on its own may not offer the solution to poor adherence in people taking TB medication.

10.1002/14651858.CD003343.pub4

cochrane-simplification-train-1003

cochrane-simplification-train-1003

We included seven RCTs (N = 923): one examined asymptomatic women with twin pregnancies; four included women with singleton pregnancies and symptoms of preterm labour (PTL); one included women with singleton pregnancies and symptoms of preterm premature rupture of membranes (PPROM); and one included asymptomatic singletons. All trials used TVU for screening. We assessed the risk of bias of the included studies as mixed, and the quality of the evidence for primary outcomes as very low for all populations. For asymptomatic women with twin pregnancies, it is uncertain whether knowledge of TVU-measured cervical length compared to no knowledge reduces PTB at less than 34 weeks (risk ratio (RR) 0.62, 95% confidence intervals (CI) 0.30 to 1.25; 1 study, 125 participants) because the quality of the evidence is very low. The results were also inconclusive for preterm birth at 36, 32, or 30 weeks; gestational age at birth, and other maternal and perinatal outcomes. Four trials examined knowledge of TVU-measured cervical length of singletons with symptoms of PTL versus no knowledge. We are uncertain of the effects because of inconclusive results and very low-quality evidence for: preterm births at less than 37 weeks (average RR 0.59, 95% CI 0.26 to 1.32; 2 studies, 242 participants; I² = 66%; Tau² = 0.23). Birth occurred about four days later in the knowledge groups (mean difference (MD) 0.64 weeks, 95% CI 0.03 to 1.25; 3 trials, 290 women). The results were inconclusive for the other outcomes for which there were available data: PTB at less than 34 or 28 weeks; birthweight less than 2500 g; perinatal death; maternal hospitalisation; tocolysis; and steroids for fetal lung maturity. The trial of singletons with PPROM (N = 92) evaluated safety of using TVU to measure cervical length in this population as its primary outcome, not its effect on management. The results were inconclusive for incidence of maternal and neonatal infections between the TVU and no ultrasound groups. In the trial of asymptomatic singletons (N = 296), in which women either received TVU or not, the results were inconclusive for preterm birth at less than 37 weeks (RR 1.27, 95% CI 0.61 to 2.61; I² = 0%), gestational age at birth, and other perinatal and maternal outcomes. We downgraded evidence for limitations in study design, inconsistency between the trials, and imprecision, due to small sample size and wide confidence intervals crossing the line of no effect. No trial compared the effect of knowledge of the CL with no knowledge of CL in other populations, such as asymptomatic women with singleton pregnancies, or symptomatic women with twin pregnancies. There are limited data on the effects of knowing the cervical length, measured by ultrasound, for preventing preterm births, which preclude us from drawing any conclusions for women with asymptomatic twin or singleton pregnancies, singleton pregnancies with PPROM, or other populations and clinical scenarios. Limited evidence suggests that knowledge of transvaginal ultrasound-measured cervical length, used to inform the management of women with singleton pregnancies and symptoms of preterm labour, appears to prolong pregnancy by about four days over women in the no knowledge groups. Future studies could look at specific populations separately (e.g. singleton versus twins; symptoms versus no symptoms of PTL), report on all pertinent maternal and perinatal outcomes, and include cost-effectiveness analyses. Most importantly, future studies should include a clear protocol for management of women based on TVU-measured cervical length.

This review assessed if knowing the cervical length can prevent preterm birth. We included seven randomised controlled studies, which involved 923 pregnant women at 14 to 32 weeks' gestation. One study included expectant mothers with twins, without any symptoms of preterm birth or labour, and looked at the number of babies born prematurely before 36 weeks. Four studies included expectant mothers of single babies with threatened preterm labour, and one study involving women with premature rupture of the membranes looked at the safety of transvaginal ultrasound. One trial included expectant mothers with singleton pregnancies who did not have any symptoms of preterm birth or labour to look at the efficacy of transvaginal ultrasound cervical length screening. All studies used transvaginal ultrasound to assess cervical length. For women with twin pregnancies and not showing symptoms of preterm birth, we are unclear of the impact of knowing the cervical length on whether babies are born before 34 weeks' gestation, or their gestational age at birth (1 study, 125 women), because we assessed the quality of the evidence to be very low. For women with a single baby and threatened preterm labour, knowledge of their cervical length may have led to a longer pregnancy by about four days (4 studies, 410 women), but the evidence on the number of babies born before 37 weeks was unclear (2 studies, 242 women). For women whose waters had broken, it is unclear whether healthcare provider knowledge makes any difference to whether the women gave birth preterm, or on the number of infections, again because we judged the quality of evidence as very low. For women with singleton pregnancies not showing symptoms of preterm birth, it is unclear whether an ultrasound to measure cervical length made any difference to whether their babies were born before 37 weeks' gestation (1 study, 296 women; very low-quality evidence). What does this mean? We found a limited number of studies including small numbers of women. The studies varied in their design and had a broad spread of results. Women were not blinded to whether they had an ultrasound or not. Currently, there is not enough high quality research to show if knowledge of cervical length in women with twin or singleton pregnancies has any effect. Future studies could include ways of managing women as a result of the cervical length results, and it would be useful to look at specific populations separately, such as single babies versus twins and women with and without symptoms of preterm labour. They could also report on all important maternal and perinatal outcomes, and include cost-effectiveness analyses.

10.1002/14651858.CD007235.pub4

cochrane-simplification-train-1004

cochrane-simplification-train-1004

We identified 30 new non-randomized cohort studies (45 comparisons): no new RCTs were found. This update now includes five RCTs (yielding 6 comparisons) and 80 non-randomized cohort studies (130 comparisons), with 86,640 patients treated in RCTs and 57,205 patients treated outside RCTs. In the randomised studies, patients were invited to participate in an RCT or not; these comparisons provided limited information because of small sample sizes (a total of 412 patients) and the nature of the questions they addressed. When the results of RCTs and non-randomized cohorts that reported dichotomous outcomes were combined, there were 98 comparisons; there was also heterogeneity (P < 0.00001, I2 = 42.2%) between studies. No statistical significant differences were found for 85 of the 98 comparisons. Eight comparisons reported statistically significant better outcomes for patients treated within RCTs, and five comparisons reported statistically significant worse outcomes for patients treated within RCTs. There was significant heterogeneity (P < 0.00001, I2 = 58.2%) among the 38 continuous outcome comparisons. No statistically significant differences were found for 30 of the 38 comparisons. Three comparisons reported statistically significant better outcomes for patients treated within RCTs, and five comparisons reported statistically significant worse outcomes for patients treated within RCTs. This review indicates that participation in RCTs is associated with similar outcomes to receiving the same treatment outside RCTs. These results challenge the assertion that the results of RCTs are not applicable to usual practice.

This updated review assessed whether there were harmful or beneficial effects from participating in randomized controlled trials (RCTs). The outcomes of patients who participated in RCTs were compared with outcomes of patients who were eligible for the trial and received similar clinical interventions, but did not participate. Comparisons were included both of 'experimental' treatment inside and outside of RCT and of 'control' treatment comparisons. On average, the outcomes of patients participating and not participating in RCTs were similar, suggesting that participation in RCTs, independent of the effects of the clinical interventions being compared, is likely to be comparable.

10.1002/14651858.MR000009.pub4

cochrane-simplification-train-1005

cochrane-simplification-train-1005

Fifteen trials were included in the review (2064 participants). Three types of photocoagulation were used in the trials: direct photocoagulation of the entire CNV (11 trials), perifoveal photocoagulation (one trial) and grid photocoagulation (three trials). In 12 trials the control group was observation only. One trial compared photocoagulation to submacular surgery and two trials compared different lasers. Data on the progression of visual loss could be extracted from five of the eight trials of direct photocoagulation of the CNV versus observation. The treatment effect was in the direction of harm in all studies at three months follow up (RR 1.41, 95% confidence intervals (CI) 1.08 to 1.82). After two years the treatment effect was in the direction of benefit (RR 0.67, 95% CI 0.53 to 0.83). These studies were clinically heterogenous with participants having CNV lesions in different locations and different baseline visual acuities. There was little evidence of statistical heterogeneity at three months but substantial statistical heterogeneity at two years. However, all treatment effects in the individual trials were in the direction of benefit. One study comparing perifoveal photocoagulation or observation of subfoveal CNV found benefits that were statistically significant only at two years (RR 0.36, 95% CI 0.18 to 0.72). Other comparisons did not demonstrate differences. In the medium to long term laser photocoagulation of CNV slows the progression of visual loss in people with neovascular AMD. However, it is associated with an increased risk of visual loss immediately after treatment and this period may be longer in people with subfoveal AMD. With the advent of modern pharmacological therapies, and concern for the impact of iatrogenic scotoma in subfoveal CNV, laser photocoagulation of subfoveal CNV is not recommended. No studies have compared photocoagulation with modern pharmacological agents for AMD for non-subfoveal CNV.

Fifteen trials involving a total of 2064 participants were included. Three types of photocoagulation were used in the trials: direct photocoagulation of the entire CNV, perifoveal photocoagulation and grid photocoagulation. Control groups in the trials included observation only, submacular surgery and different lasers. This review found that the use of photocoagulation is effective for people with lesions that are outside the centre of the macula. However, these types of lesions are less common in AMD. Severe loss of vision can be prevented in about one in six people.

10.1002/14651858.CD004763.pub2

cochrane-simplification-train-1006

cochrane-simplification-train-1006

Twenty-two trials with 12,455 participants randomised (9595 used in analyses) were included. For the 13 that contributed data for the permanent tooth surfaces meta-analysis, the pooled D(M)FS prevented fraction estimate comparing fluoride varnish with placebo or no treatment was 43% (95% confidence interval (CI) 30% to 57%; P < 0.0001). There was substantial heterogeneity, confirmed statistically (P < 0.0001; I2 = 75%), however this body of evidence was assessed as of moderate quality. The pooled d(e/m)fs prevented fraction estimate was 37% (95% CI 24% to 51%; P < 0.0001) for the 10 trials that contributed data for the primary tooth surfaces meta-analysis, also with some heterogeneity (P = 0.009; I2 = 59%). Once again this body of evidence was assessed as of moderate quality. No significant association between estimates of D(M)FS or d(e/m)fs prevented fractions and the pre-specified factors of baseline caries severity, background exposure to fluorides, application features such as prior prophylaxis, concentration of fluoride, frequency of application were found. There was also no significant association between estimates of D(M)FS or d(e/m)fs prevented fractions and the post hoc factors: whether a placebo or no treatment control was used, length of follow-up, or whether individual or cluster randomisation was used, in the meta-regression models. A funnel plot of the trials in the main meta-analyses indicated no clear relationship between prevented fraction and study precision. In both methods, power is limited when few trials are included. There was little information concerning possible adverse effects or acceptability of treatment. The conclusions of this updated review remain the same as those when it was first published. The review suggests a substantial caries-inhibiting effect of fluoride varnish in both permanent and primary teeth, however the quality of the evidence was assessed as moderate, as it included mainly high risk of bias studies, with considerable heterogeneity.

This review of existing studies was carried out by the Cochrane Oral Health Group and the evidence is current up to 13 May 2013. In this updated review there are now 22 trials published between 1975 and 2012 in which a total of 12,455 children were randomised to treatment with either fluoride varnish or placebo/no treatment. Study duration ranged from one to five years among included trials (12 of these lasted two years). The evidence produced has been found to be of moderate quality due to issues with trial designs. However in the 13 trials that looked at children and adolescents with permanent teeth the review found that the young people treated with fluoride varnish experienced on average a 43% reduction in decayed, missing and filled tooth surfaces. In the 10 trials looking at the effect of fluoride varnish on first or baby teeth the evidence suggests a 37% reduction in decayed, missing and filled tooth surfaces. There was little information concerning possible adverse effects or acceptability of treatment. The evidence presented is of moderate quality due to issues with trial designs.

10.1002/14651858.CD002279.pub2

cochrane-simplification-train-1007

cochrane-simplification-train-1007

We identified three randomised trials with 261 participants for inclusion. The risk of bias was low in one and high in two trials. Two of the randomised trials compared PEI versus PAI; we included 185 participants in the analysis. The overall survival (HR 1.47; 95% confidence interval (CI) 0.68 to 3.19) and recurrence-free survival (HR 1.42; 95% CI 0.68 to 2.94) were not statistically significantly different between the intervention groups of the two trials. Trial sequential analysis for the comparison PEI versus PAI including two trials revealed that the number of participants that were included in the trials were insufficient in order to judge a relative risk reduction of 20%. Data on the duration of hospital stay were available from one trial for the comparison PEI versus PAI showing a significantly shorter hospital stay for the participants treated with PEI (mean 1.7 days; range 2 to 3 days) versus PAI (mean 2.2 days; range 2 to 5 days). Quality of life was not reported. There were only mild adverse events in participants treated with either PEI or PAI such as transient fever, flushing, and local pain. One randomised trial compared PEI versus surgery; we included 76 participants in the analyses. There was no significant difference in the overall survival (HR 1.57; 95% CI 0.53 to 4.61) and recurrence-free survival (HR 1.35; 95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group while three postoperative deaths occurred in the surgery group. In addition to the three randomised trials, we identified one quasi-randomised study comparing PEI versus PAI. Due to methodological flaws of the study, we extracted only the data on adverse events and presented them in a narrative way. We found no randomised trials that compared PEI or PAI versus no intervention, best supportive care, sham intervention, or other percutaneous local ablative therapies excluding RFTA. We found also no randomised clinical trials that compared PAI versus other interventional treatments or surgery. We identified two ongoing randomised clinical trials. One of these two trials compares PEI versus surgery and the other PEI versus transarterial chemoembolization. To date, it is unclear whether the trials will be eligible for inclusion in this meta-analysis as the data are not yet available. This review will not be updated until new randomised clinical trials are published and can be used for analysis. PEI versus PAI did not differ significantly regarding benefits and harms in people with early HCC, but the two included trials had only a limited number of participants and one trial was judged a high risk of bias. Thus, the current evidence precludes us from making any firm conclusions. There was also insufficient evidence to determine whether PEI versus surgery (segmental liver resection) was more effective, because conclusions were based on a single randomised trial. While some data from this single trial suggested that PEI was safer, the high risk of bias and the lack of any confirmatory evidence make a reliable assessment impossible. We found no trials assessing PEI or PAI versus no intervention, best supportive care, or sham intervention. There is a need for more randomised clinical trials assessing interventions for people with early stage HCC. Such trials should be conducted with low risks of systematic errors and random errors.

The review authors searched the medical literature in order to clarify the role of PEI and PAI for the treatment of liver cancer and to compare their benefits and harms with no treatment, with placebo (a pretend treatment), or with other treatments (such as laser, cryoablation, or microwave ablation; hepatic resection; and liver transplantation). We collected and analysed data from randomised clinical trials (where people were allocated at random to one of two or more treatments groups) of people with liver cancer who were able to receive PEI or PAI. Evidence is current to July 2014. The review authors only identified three randomised trials with 261 participants. The risk of bias was low in one and high in two trials. We found two trials that compared PEI versus PAI and one trial that compared PEI versus surgery. We found no trials that compared PEI or PAI versus sham (pretend) intervention, best supportive care, cryotherapy, laser-induced thermotherapy, or high-frequency ultrasound. We found no randomised trials that compared PAI versus surgery. The review authors found low-quality evidence suggesting that PEI yielded the same result as PAI regarding overall survival (the length of time that the person remains alive) and recurrence-free survival (time that the person remains free of cancer). We calculated the number of participants that would be required to judge a relative risk reduction (relative risk is a comparison of the risk of an event happening for one treatment group compared with another treatment group) for survival of 20%. We found that for the comparisons PEI versus PAI, the number of participants was too low to reach valid conclusions. In both groups, participants reported the occurrence of mild side effects such as transient fever, flushing, and local pain. Based on one randomised trial with high risk of bias, there was very low quality evidence that surgical resection does not seem to be superior to PEI in people with early liver cancer. Of note, no severe side effects occurred in people treated with PEI while there were three postoperative deaths in people treated surgically. Again, too few participants were randomised to claim or reject important differences. There is a need for more randomised clinical trials assessing interventions for people with early-stage liver cancer. Such trials should be conducted with low risks of bias (systematic errors, that is overestimation of benefits and underestimation of harms) and of play of chance (random errors, that is errors due to too few participants and too few outcomes).

10.1002/14651858.CD006745.pub3

cochrane-simplification-train-1008

cochrane-simplification-train-1008

We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE. Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less likely to have missed days of therapy (OR 0.36; 95% CI 0.25 to 0.51). Of four vaginal ring trials, one found ring users had more noncompliance (OR 3.99; 95% CI 1.87 to 8.52), while another showed more compliance with the regimen (OR 1.67; 95% CI 1.04 to 2.68). More patch users discontinued early than COC users. ORs from two meta-analyses were 1.59 (95% CI 1.26 to 2.00) and 1.56 (95% CI 1.18 to 2.06) and another trial showed OR 2.57 (95% CI 0.99 to 6.64). Patch users also had more discontinuation due to adverse events than COC users. Users of the norelgestromin-containing patch reported more breast discomfort, dysmenorrhea, nausea, and vomiting. In the levonorgestrel-containing patch trial, patch users reported less vomiting, headaches, and fatigue. Of 11 ring trials with discontinuation data, two showed the ring group discontinued less than the COC group: OR 0.32 (95% CI 0.16 to 0.66) and OR 0.52 (95% CI 0.31 to 0.88). Ring users were less likely to discontinue due to adverse events in one study (OR 0.32; 95% CI 0.15 to 0.70). Compared to the COC users, ring users had more vaginitis and leukorrhea but less vaginal dryness. Ring users also reported less nausea, acne, irritability, depression, and emotional lability than COC users. For cycle control, only one trial study showed a significant difference. Women in the patch group were less likely to have breakthrough bleeding and spotting. Seven ring studies had bleeding data; four trials showed the ring group generally had better cycle control than the COC group. Effectiveness was not significantly different for the methods compared. Pregnancy data were available from half of the patch trials but two-thirds of ring trials. The patch could lead to more discontinuation than the COC. The patch group had better compliance than the COC group. Compliance data came from half of the patch studies and one-third of the ring trials. Patch users had more side effects than the COC group. Ring users generally had fewer adverse events than COC users but more vaginal irritation and discharge. The quality of the evidence for this review was considered low for the patch and moderate for the ring. The main reasons for downgrading were lack of information on the randomization sequence generation or allocation concealment, the outcome assessment methods, high losses to follow up, and exclusions after randomization.

Through February 2013, we did computer searches for randomized controlled trials of the skin patch or vaginal ring compared to pills for birth control. Pills included types with both estrogen and progestin. We wrote to researchers to find other trials. We found 18 trials. Of six patch trials, five compared the marketed patch to birth control pills and one studied a patch being developed. Of 12 ring trials, 11 looked at the marketed ring and pills while one studied a ring being developed. The methods compared had similar pregnancy rates. Patch users reported using their method more consistently than the pill group did. Only half of the patch studies had data on pregnancy or whether the women used the method correctly. However, most of the ring studies had those data. Patch users were more likely than pill users to drop out early from the trial. Ring users were not more likely to drop out early. Compared to pill users, users of the marketed patch had more breast discomfort, painful periods, nausea, and vomiting. Ring users had more vaginal irritation and discharge than pill users but less nausea, acne, irritability, depression, and emotional changes. Ring users often had fewer bleeding problems than pill users. The quality of information was classed as low for the patch trials and moderate for the ring studies. Lower quality was due to not reporting how groups were assigned or not having good outcome measures. Other issues were high losses and taking assigned women out of the analysis. Studies of the patch and ring should provide more detail on whether women used the method correctly.

10.1002/14651858.CD003552.pub4

cochrane-simplification-train-1009

cochrane-simplification-train-1009

Thirty-three small studies ( 2267 patients) compared different fusion techniques. The major treatments were discectomy alone, addition of an interbody fusion procedure (autograft, allograft, cement, or cage), and addition of anterior plates. Eight studies had a low risk of bias. Few studies reported on pain, therefore, at best, there was very low quality evidence of little or no difference in pain relief between the different techniques. We found moderate quality evidence for these secondary outcomes: no statistically significant difference in Odom's criteria between iliac crest autograft and a metal cage (6 studies, RR 1.11 (95% CI 0.99 to1.24)); bone graft produced more effective fusion than discectomy alone (5 studies, RR 0.22 (95% CI 0.17 to 0.48)); no statistically significant difference in complication rates between discectomy alone and iliac crest autograft (7 studies, RR 1.56 (95% CI 0.71 to 3.43)); and low quality evidence that iliac crest autograft results in better fusion than a cage (5 studies, RR 1.87 (95% CI 1.10 to 3.17)); but more complications (7 studies, RR 0.33 (95% CI 0.12 to 0.92)). When the working mechanism for pain relief and functional improvement is fusion of the motion segment, there is low quality evidence that iliac crest autograft appears to be the better technique. When ignoring fusion rates and looking at complication rates, a cage has a weak evidence base over iliac crest autograft, but not over discectomy alone. Future research should compare additional instrumentation such as screws, plates, and cages against discectomy with or without autograft.

This review of 33 small studies (2267 participants) evaluated fusion techniques used to treat degenerative disc disease. The major treatments were discectomy (removal of the damaged disc) alone, addition of a fusion procedure (bone transplanted from another part of the body, cement, or cage), and addition of a plate. None of the evidence from this systematic review indicates that one technique is better than another for clinically significant pain relief for patients with chronic cervical degenerative disc disease or disc herniation. The choice for a specific technique cannot be made on the most important aspect, pain relief, which was the primary outcome parameter in our review. There is moderate quality evidence that there was little or no difference in Odom’s criteria (a tool that measures the success of the surgery at relieving the symptoms that were troublesome prior to the surgery) between those who received a bone transplant from the hip and a metal cage to help with fusion. There is moderate quality evidence that the use of a bone graft (bone transplanted from another part of the body) is more effective than discectomy alone in achieving fusion. There is low quality evidence that transplanting bone from the iliac crest is more effective in achieving fusion than using a cage, while cages are more effective in preventing complications. Further research is very likely to have an important impact on the results and our confidence in them.

10.1002/14651858.CD004958.pub2

cochrane-simplification-train-1010

cochrane-simplification-train-1010

We included three studies involving 1879 participants: two RCTs and one cluster-RCT. Interventions consisted of: · patient workshop and individual coaching using behaviour change techniques; · individual patient coaching utilising cognitive-behavioural therapy and motivational interviewing; and · holistic patient review, multi-disciplinary practitioner training, and organisational change. No studies reported the primary outcome ‘patient involvement in decision-making’ or the primary adverse outcome ‘less patient involvement as a result of the intervention’. Comparing interventions (patient workshop and individual coaching, holistic patient review plus practitioner training, and organisational change) to usual care: we are uncertain whether interventions had any effect on patient reports of high self-rated health (risk ratio (RR) 1.40, 95% confidence interval (CI) 0.36 to 5.49; very low-certainty evidence) or on patient enablement (mean difference (MD) 0.60, 95% CI -9.23 to 10.43; very low-certainty evidence) compared with usual care. Interventions probably had no effect on health-related quality of life (adjusted difference in means 0.00, 95% CI -0.02 to 0.02; moderate-certainty evidence) or on medication adherence (MD 0.06, 95% CI -0.05 to 0.17; moderate-certainty evidence) but probably improved the number of patients discussing their priorities (adjusted odds ratio 1.85, 95% CI 1.44 to 2.38; moderate-certainty evidence) and probably increased the number of nurse consultations (incident rate ratio from adjusted multi-level Poisson model 1.37, 95% CI 1.17 to 1.61; moderate-certainty evidence) compared with usual care. Practitioner outcomes were not measured. Interventions were not reported to adversely affect rates of participant death or anxiety, emergency department attendance, or hospital admission compared with usual care. Comparing interventions (patient workshop and coaching, individual patient coaching) to attention-control conditions: we are uncertain whether interventions affect patient-reported high self-rated health (RR 0.38, 95% CI 0.15 to 1.00, favouring attention control, with very low-certainty evidence; RR 2.17, 95% CI 0.85 to 5.52, favouring the intervention, with very low-certainty evidence). We are uncertain whether interventions affect patient enablement and engagement by increasing either patient activation (MD 1.20, 95% CI -8.21 to 10.61; very low-certainty evidence) or self-efficacy (MD 0.29, 95% CI -0.21 to 0.79; very low-certainty evidence); or whether interventions affect the number of general practice visits (MD 0.51, 95% CI -0.34 to 1.36; very low-certainty evidence), compared to attention-control conditions. The intervention may however lead to more patient-reported changes in management of their health conditions (RR 1.82, 95% CI 1.35 to 2.44; low-certainty evidence). Practitioner outcomes were not measured. Interventions were not reported to adversely affect emergency department attendance nor hospital admission when compared with attention control. Comparing one form of intervention with another: not measured. There was 'unclear' risk across studies for performance bias, detection bias, and reporting bias; however, no aspects were 'high' risk. Evidence was downgraded via GRADE, most often because of 'small sample size' and 'evidence from a single study'. Limited available evidence does not allow a robust conclusion regarding the objectives of this review. Whilst patient involvement in decision-making is seen as a key mechanism for improving care, it is rarely examined as an intervention and was not measured by included studies. Consistency in design, analysis, and evaluation of interventions would enable a greater likelihood of robust conclusions in future reviews.

We included research published up until August 2018. We found three relevant studies involving 1879 participants. These studies were reported from three countries. Participants were over 65 years of age with three or more long-term health problems on average. Interventions investigated included: · patient workshops and individual patient coaching; · patient coaching including cognitive-behavioural therapy; and · whole-person patient review, practitioner training, and organisational changes. All studies were funded by national research bodies. None of the studies reported the main outcome ‘patient involvement in decision-making about their health care’ nor whether there was less patient involvement as a result of the intervention. Interventions were not found to increase adverse outcomes such as death, anxiety, emergency department attendance, or hospital admissions.. We are uncertain whether interventions for involving older people with more than one long-term health problem in decision-making about their health care can improve their self-rated health or healthcare engagement, or make any difference in self-efficacy (one's belief in one's ability to succeed in specific situations) or in the overall number of general practice visits. We can report that these interventions probably make little or no difference in patients' quality of life but probably increase the number of patients discussing their priorities, and are associated with more patient consultations with nurses, when compared to usual care. Interventions may be associated with more changes in the management of health conditions when considered from the patient’s perspective when compared with a control group. The quality of the evidence was limited by small studies, and by studies choosing to measure different outcomes, resulting in lack of data that could be combined in analyses. Further research in this developing area is required before firm conclusions can be drawn.

10.1002/14651858.CD013124.pub2

cochrane-simplification-train-1011

cochrane-simplification-train-1011

We included 15 studies. Fourteen studies reported data per woman (2894 women) and one study reported data per cycle (969 cycles). The quality of the evidence using the GRADE approach ranged from moderate quality to very low quality. The main reasons for downgrading evidence were poor methodological reporting, selective reporting, inconsistency and imprecision. Live birth per woman - Overall, there was no evidence of a difference in live birth rate between Day three and Day two embryo transfer (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.89 to 1.23; three studies, n = 1200 women; I2 = 63%; very low quality evidence). The data suggest that if 32% of women who underwent a Day two embryo transfer had a live birth, then between 28% to 39% of women undergoing a Day three embryo transfer would have a live birth. Ongoing pregnancy per woman - There was no evidence of a difference between Day three and Day two embryo transfer for ongoing pregnancy (RR 0.98, 95% CI 0.85 to 1.12; six studies, n = 1740 women; I2 = 52%; very low quality of evidence). The data suggest that if 33% of women undergoing a Day two embryo transfer had an ongoing pregnancy then between 28% to 37% of women undergoing a Day three embryo transfer would have an ongoing pregnancy. Clinical pregnancy per woman - There was no evidence of a difference between Day three and Day two embryo transfer for the chance of a clinical pregnancy (RR 1.08, 95% CI 0.98 to 1.19; 12 studies, n = 2461, I2 = 51%; very low quality evidence). The data suggest that if 39% of women undergoing Day two embryo transfer had a clinical pregnancy, then between 38% to 46% of women undergoing a Day three embryo transfer would have a clinical pregnancy. Multiple pregnancy per woman - There was no evidence of a difference between Day three and Day two embryo transfer for the risk of a multiple pregnancy (RR 1.12, 95% CI 0.86 to 1.44; eight studies, n = 1837; I2 = 0%; moderate quality evidence). The data suggest that if 11% of women undergoing Day two embryo transfer had a multiple pregnancy, then between 9% to 15% of women undergoing a Day three embryo transfer would have a multiple pregnancy. Miscarriage rate per woman - There was no evidence of a difference between Day three and Day two embryo transfer for the risk of miscarriage (RR 1.16, 95% CI 0.84 to 1.60; nine studies, n = 2153 women, I2 = 26%; moderate quality evidence). The data suggest that if 6% of women undergoing Day two embryo transfer had a miscarriage, then between 5% to 10% of women undergoing a Day three embryo transfer would have a miscarriage. Ectopic pregnancy rate per woman - There was no evidence of a difference between Day three and Day two embryo transfer for the risk of ectopic pregnancy (RR 0.99, 95% CI 0.29 to 3.40; six studies, n = 1531 women, I2 = 0%; low quality evidence). The data suggest that if 0.7% of women undergoing Day two embryo transfer have an ectopic pregnancy, then between 0.2% to 2% of women undergoing Day three embryo transfer would have an ectopic pregnancy. Subgroup analysis for pregnancy outcomes did not identify any differential effect between IVF and ICSI. None of the included studies prespecified complication rate (e.g. OHSS), fetal abnormality or women's evaluation of the procedure as outcomes in their studies. Twelve of 15 studies contributed data that could be included in meta-analyses. The quality of the evidence ranged from moderate to very low. Only three of the 15 studies reported data for live birth, although the data for ongoing pregnancy and clinical pregnancy are consistent with the live birth data, suggesting no difference between Day three and Day two embryo transfer for these outcomes. There was no evidence of a difference identified between Day three and Day two embryo transfer for multiple pregnancy, miscarriage or ectopic pregnancy per woman randomised. No data were reported for complication rate, fetal abnormality or woman's evaluation of the procedure. The current evidence has not identified any evidence of differences in pregnancy outcomes between Day two and Day three embryo transfers. Any further studies comparing these timings of embryo transfer are unlikely to alter the findings and we suggest that this review no longer be updated.

We identified 15 randomised trials meeting the review inclusion criteria. These include 14 trials reporting data from 2894 women; one trial reported data from 969 cycles so could not be included in meta-analysis. All of the included studies were parallel-design randomised controlled trials conducted in Brazil, Chile, Singapore, Argentina, Finland, Turkey, Spain, Israel, Canada, Greece, Japan, Italy, Norway and Belgium. The evidence is current to April 2016. Only three of 15 studies reported on live birth as an outcome. We found that there was no clear evidence of a difference between Day three and Day two embryo transfer for rates of live birth, ongoing pregnancy, clinical pregnancy, multiple pregnancy or miscarriage. There were no data reported for complication rate, fetal abnormality or women's evaluation of the procedure. Allocation concealment was poorly reported in the included studies and blinding was not possible (although we feel this is unlikely to affect pregnancy outcomes). Blinding of outcome assessors was not reported. The quality of the evidence ranged from moderate to very low. The main reasons for downgrading the evidence were poor reporting of study methods (risk of bias), lack of agreement between studies (inconsistency), low event rates and lack of accuracy (imprecision) for some outcomes and poor reporting of live birth outcomes (selective reporting). Any further studies comparing these timings of embryo transfer are unlikely to alter the findings and we do not plan to update this review again. Many of the trials included in this review have used outdated techniques that include stimulation, laboratory technology and transferring more than one embryo. We would direct the reader to the Glujovsky 2016 Cochrane review comparing Day 2/3 with day 5/6 embryo transfer.

10.1002/14651858.CD004378.pub3

cochrane-simplification-train-1012

cochrane-simplification-train-1012

We included a total of 22 trials (9137 participants) of which 15 were randomized trials (7762 participants). The overall risk of bias was mostly unclear or high due to selection and performance bias. We used GRADE to assess the quality of the evidence and this was downgraded from high to moderate or very low due to the risk of bias, imprecision or indirectness. The rate of PE in the studies comparing IPC alone with combined IPC and pharmacological prophylaxis was low, underpowering the analyses. The incidence of symptomatic PE was 0.79% with IPC, but ranged between 0.1 to 1% with combined IPC and pharmacological prophylaxis (OR 0.49, 95% CI 0.18 to 1.34; 12 studies, 3017 participants, moderate quality evidence). The incidence of DVT was 4.10% in the IPC group and 2.19% in the combined group showing a reduced incidence of DVT in favour of the combined group (OR 0.52, 95% CI 0.33 to 0.82; 11 studies, 2934 participants, moderate quality evidence). The addition of an anticoagulant to IPC, however, increased the risk of any bleeding compared to IPC alone; 0.66% (7/1053) in the IPC group and 4.0% (44/1102) in the combined group (OR 5.04, 95% CI 2.36 to 10.77; 7 studies, 2155 participants, moderate quality evidence). Major bleeding followed a similar pattern; 0.1% (1/1053) in the IPC group to 1.5% (17/1102) in the combined group (OR 6.81, 95% CI 1.99 to 23.28; 7 studies, 2155 participants, moderate quality evidence). We detected no difference between the type of surgery subgroups such as orthopedic and non-orthopedic participants for DVT incidence (P = 0.16). Tests for differences between type of surgery subgroups were not possible for PE incidence. Compared with pharmacological prophylaxis alone, the use of combined IPC and pharmacological prophylaxis modalities reduced the incidence of symptomatic PE from 2.92% to 1.20% (OR 0.39, 95% CI 0.23 to 0.64; 10 studies, 3544 participants, moderate quality evidence). The incidence of DVT was 6.2% in the pharmacological prophylaxis group and 2.9% in the combined group showing no difference between the combined and pharmacological prophylaxis groups (OR 0.42, 95% CI 0.18 to 1.03; 11 studies, 2866 participants, moderate quality evidence). Increased bleeding side effects were not observed for IPC when it was added to anticoagulation (bleeding: OR 0.80, 95% CI 0.30 to 2.14, very low quality evidence; major bleeding: OR 1.21, 95% CI 0.35 to 4.18, very low quality evidence, 3 studies, 244 participants). No difference was detected between the type of surgery subgroups for PE incidence (P = 0.68) or for DVT incidence (P = 0.10). Moderate quality evidence suggests that combining IPC and pharmacological prophylaxis, compared with IPC or pharmacological prophylaxis alone, decreases the incidence of DVT when compared to compression, and incidence of PE when compared to anticoagulation. Moderate quality evidence suggests that there is no difference between combined and single modalities in the incidence of PE when compared with compression alone and DVT when compared with anticoagulation alone. The quality of evidence for PE or DVT was downgraded to moderate due to imprecision or risk of bias in study methodology, highlighting the need for further research. Moderate quality evidence suggests the addition of pharmacological prophylaxis to IPC, increased the risk of bleeding compared to IPC alone, a side effect not observed for IPC when added to pharmacological prophylaxis (very low quality evidence), as expected for a physical method of thromboprophylaxis. The quality of evidence for bleeding was downgraded to moderate due to indirectness or very low due to risk of bias in study methodology, indirectness and imprecision highlighting the need for further research. Nevertheless, the results of the current review agree with current guideline recommendations, which support the use of combined modalities in hospitalised patients (limited to those with trauma or undergoing surgery) at risk of developing VTE. More studies on the role of combined modalities in VTE prevention are needed.

We identified 22 trials with a total of 9137 participants to include in this review (current until May 2016). The mean age of participants, where reported, was 65.2 years. Most participants had either a high-risk procedure or condition. The predisposing conditions were orthopedic surgery in 12 studies and urology, cardiothoracic, neurosurgery, trauma, general surgery, gynaecology or other types of participants in the remaining studies. Compared to IPC alone, IPC plus medication did not show differences in the incidence (rate of new cases) of PE (12 studies with a total of 3017 participants). The incidence of DVT was reduced for IPC combined with medication when compared with IPC alone (11 studies with a total of 2934 participants). The addition of a medication to IPC, however, increased the risk for any bleeding compared to IPC alone, from 0.66% to 4.0%. Major bleeding followed a similar pattern, with an increase from 0.1% to 1.5%.Further analysis looking at different subgroups of participants (orthopedic and non-orthopedic participants) did not show any overall difference in DVT while it was not possible to assess differences between subgroups for PE. Compared with medication alone, combined IPC and medication reduced the incidence of PE (10 studies with 3544 participants). DVT incidence was not different between the medication and the combined IPC and medication group (11 studies with 2866 participants). No differences were observed in rates of bleeding (three studies with 244 participants). Further analysis looking at different subgroups of participants did not show any overall difference in incidence of PE and DVT between orthopedic and non-orthopedic participants. The findings of this review show moderate quality evidence and agree with current guideline recommendations supporting the use of combined IPC and pharmacological prophylaxis, compared with IPC or pharmacological prophylaxis alone, to reduce the incidence of DVT and PE in hospitalized patients. Moderate quality evidence suggests the addition of pharmacological prophylaxis to IPC, increased the risk of bleeding compared to IPC alone, a side effect not observed for IPC when added to pharmacological prophylaxis (very low quality evidence), as expected for a physical method for preventing blood clots. The quality of the evidence was downgraded from high to moderate or very low for risk of bias and imprecision and indirectness between the studies.

10.1002/14651858.CD005258.pub3

cochrane-simplification-train-1013

cochrane-simplification-train-1013

Three trials with 144 participants met the inclusion criteria. Two of the trials had a randomised cross-over design, one was a cross-over trial which we classified as quasi-randomised. Participants in the included studies were people with dementia living in nursing homes. They were predominantly women and had a mean age of over 80 years. SPT was performed using an audio or video recording prepared by family members or surrogates. It varied in its content, frequency of administration and duration. All the studies compared multiple treatments. In one study, SPT was compared with two other interventions; in the other two studies, it was compared with three other interventions. Specifically, SPT was compared to usual care, personalised music (two studies), a 'placebo' audiotape containing the voice of a person (two studies), and one-to-one social interaction performed by trained research assistants (one study). In terms of outcomes evaluated, one study considered agitation and withdrawn behaviour (both assessed with three methods); the second study evaluated verbal disruptive behaviour (assessed with three methods); and the third study evaluated physically agitated behaviour and verbally agitated behaviour (the method used was not clearly described). According to the GRADE criteria, the overall quality of the evidence was very low due to very small numbers of participants and risk of bias in the included studies; (none of the trials was at low risk of selection bias; all the trials were at high risk of performance bias; one trial was at high risk of attrition bias; and all had unclear selective reporting). Because of variation in the participants, the format of SPT, the comparison interventions, and the measures used to assess outcomes, we judged the results unsuitable for a meta-analysis. Within each trial, the effect of SPT on behaviour, compared to usual care, was mixed and depended on the measure used. Two trials which included a personalised music intervention reported no significant differences between simulated presence and music on behavioural outcomes. Because the overall quality of the evidence was very low, we were very uncertain regarding all the results None of the studies evaluated quality of life or any of our secondary outcome measures (performance of activities of daily living, dropout and carer burden). We were unable to draw any conclusions about the efficacy of SPT for treating behavioural and psychological symptoms and improving quality of life of people with dementia. New high-quality studies are needed to investigate the effect of SPT.

We looked for trials which compared SPT to usual care or to another treatment. Ideally, people with dementia should have been randomly allocated to one or other treatment, but we also included trials even if treatment allocation was not strictly random. We found three trials which met our inclusion criteria. The 144 participants were all living in nursing homes. The majority were women with an average age of over 80 years and severe dementia. The way SPT was administered was different in each trial. All the trials used more than one comparison treatment, which differed between trials. The trials all attempted to measure an effect on agitated behaviours, but used different approaches. Because the trials were so different from each other, we were not able to pool the results. Individually, each trial reported different methods to assess the effect of SPT on behavioural problems and the results varied depending on the method used to measure the outcome. None of the studies assessed quality of life, effect on daily activities, effects on caregivers, or how likely participants were to drop out of the study. The studies were small and all had problems with their methods which could have biased their results. Hence, we thought the overall quality of the evidence was very low, meaning we cannot be at all confident in the results. Not enough high-quality research has been done to allow us to judge whether SPT can help people with dementia who are distressed or agitated.

10.1002/14651858.CD011882.pub2

cochrane-simplification-train-1014

cochrane-simplification-train-1014

We included 28 studies, comprising 17 RCTs, 5 Q-RCTs and 6 ITS studies. Most (21/28) took place in the USA, and 19 took place in university settings, 14 of which mainly involved university students or staff. Most (20/28) studies assessed the impact of labelling on menus or menu boards, or nutritional labelling placed on, or adjacent to, a range of foods or drinks from which participants could choose. Eight studies provided participants with only one labelled food or drink option (in which labelling was present on a container or packaging, adjacent to the food or on a display board) and measured the amount consumed. The most frequently assessed labelling type was energy (i.e. calorie) information (12/28). Eleven studies assessed the impact of nutritional labelling on purchasing food or drink options in real-world settings, including purchases from vending machines (one cluster-RCT), grocery stores (one ITS), or restaurants, cafeterias or coffee shops (three RCTs, one Q-RCT and five ITS). Findings on vending machines and grocery stores were not interpretable, and were rated as very low quality. A meta-analysis of the three RCTs, all of which assessed energy labelling on menus in restaurants, demonstrated a statistically significant reduction of 47 kcal in energy purchased (MD −46.72 kcal, 95% CI −78.35, −15.10, N = 1877). Assuming an average meal of 600 kcal, energy labelling on menus would reduce energy purchased per meal by 7.8% (95% CI 2.5% to 13.1%). The quality of the evidence for these three studies was rated as low, so our confidence in the effect estimate is limited and may change with further studies. Of the remaining six studies, only two (both ITS studies involving energy labels on menus or menus boards in a coffee shop or cafeteria) were at low risk of bias, and their results support the meta-analysis. The results of the other four studies which were conducted in a restaurant, cafeterias (2 studies) or a coffee shop, were not clearly reported and were at high risk of bias. Seventeen studies assessed the impact of nutritional labels on consumption in artificial settings or scenarios (henceforth referred to as laboratory studies or settings). Of these, eight (all RCTs) assessed the effect of labels on menus or placed on a range of food options. A meta-analysis of these studies did not conclusively demonstrate a reduction in energy consumed during a meal (MD −50 kcal, 95% CI −104.41, 3.88, N = 1705). We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies. Six laboratory studies (four RCTs and two Q-RCTs) assessed the impact of labelling a single food or drink option (such as chocolate, pasta or soft drinks) on energy consumed during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant difference in energy (kcal) consumed (SMD 0.05, 95% CI −0.17 to 0.27, N = 732). However, the confidence intervals were wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies. There was no evidence that nutritional labelling had the unintended harm of increasing energy purchased or consumed. Indirect evidence came from five laboratory studies that involved mislabelling single nutrient content (i.e. placing low energy or low fat labels on high-energy foods) during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant increase in energy (kcal) consumed (SMD 0.19, 95% CI −0.14to 0.51, N = 718). The effect was small and the confidence intervals wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence from these studies as very low, providing very little confidence in the effect estimate. Findings from a small body of low-quality evidence suggest that nutritional labelling comprising energy information on menus may reduce energy purchased in restaurants. The evidence assessing the impact on consumption of energy information on menus or on a range of food options in laboratory settings suggests a similar effect to that observed for purchasing, although the evidence is less definite and also of low quality. Accordingly, and in the absence of observed harms, we tentatively suggest that nutritional labelling on menus in restaurants could be used as part of a wider set of measures to tackle obesity. Additional high-quality research in real-world settings is needed to enable more certain conclusions. Further high-quality research is also needed to address the dearth of evidence from grocery stores and vending machines and to assess potential moderators of the intervention effect, including socioeconomic status.

Some studies assessed buying food or drinks from vending machines, grocery stores, restaurants, cafeterias, or coffee shops. Others assessed the amount of food or drink consumed during a snack or meal in an artificial setting or scenario (referred to as laboratory studies or settings). What are the main results of the review? Nutritional labelling on restaurant menus reduced the amount of energy (i.e. calories) purchased, but the quality of the three studies that contributed to this finding was low, so our confidence in the effect estimate is limited and may change with further studies. Eight studies assessed this same type of intervention in laboratory settings, but instead of evaluating how much energy participants purchased, these studies evaluated how much energy participants consumed. These studies did not conclusively demonstrate a reduction in energy consumed when menus or foods were labelled, and they were also of low quality. In addition, six laboratory studies assessed how much energy participants consumed when they were given one food or drink option with or without labels, and five laboratory studies assessed how much energy participants consumed when foods were experimentally labelled as low energy or low fat when they were actually high-energy foods (i.e. mislabelling). Results from these two groups of studies were inconclusive and of low, or in the case of mislabelling studies, very low quality. We found some studies that assessed labelling on vending machines and grocery stores, but their results were not easy to interpret, so we could not use them to inform this review. How up-to-date is this review? The evidence is current to 26 April 2017.

10.1002/14651858.CD009315.pub2

cochrane-simplification-train-1015

cochrane-simplification-train-1015

We included 20 studies with 1401 surgical participants comparing an α-2 agonist against a control. Thirteen studies compared clonidine with a control, whilst seven compared dexmedetomidine with a control. The doses, methods, and time of administration varied between studies: three studies gave the drug orally or as an intravenous bolus preoperatively and nine intraoperatively; one study gave the drug as an infusion starting preoperatively and seven started at varying points from anaesthetic induction to the end of surgery. Whilst all the studies were described as randomized, many provided insufficient detail on methods used. We had anticipated that attempts would be made to reduce performance bias by blinding of personnel and participants, however this was detailed in only six of the papers. Similarly, in some studies detail was lacking on methods to reduce the risk of detection bias. We therefore downgraded the quality of evidence in our 'Summary of findings' table by one level for risk of bias using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. All 20 included studies presented outcome data for postoperative shivering, and in meta-analysis α-2 agonists were shown to significantly reduce the risk of shivering (Mantel-Haenszel risk ratio 0.28, 95% confidence interval 0.18 to 0.43, P value < 0.0001). We found significant evidence of heterogeneity (I2 = 80%) for this result that was not explained by sensitivity or subgroup analysis; we therefore downgraded the inconsistency of the evidence by one level. Although we did not feel that there were concerns with imprecision or indirectness of the data, we downgraded the quality of the evidence for the risk of publication bias following visual analysis of a funnel plot. Using GRADEpro, we rated the overall quality of the data for shivering as very low. Only one study reported the incidence of core hypothermia, whilst 12 studies measured core temperature. However, as the results for core temperature were reported in different styles, pooling the results was inappropriate. We found no studies with participant-reported outcomes such as experience of shivering or participant satisfaction. We found limited data for the outcomes of length of stay in the postanaesthetic care unit (three studies, 200 participants) and the following adverse effects: sedation (nine studies, 875 participants), bradycardia (eight studies, 716 participants), and hypotension (seven studies, 688 participants). Unpooled analysis suggested that sedation and bradycardia were significantly more common with dexmedetomidine than placebo, with all seven dexmedetomidine studies and none of the clonidine studies reporting statistically significantly higher levels of sedation as an adverse effect. There is evidence that clonidine and dexmedetomidine can reduce postoperative shivering, but patients given dexmedetomidine may be more sedated. However, our assessment of the quality of this evidence is very low.

The evidence is current up to 13 June 2014. We found 20 relevant randomized controlled trials with 1401 participants undergoing surgical procedures with general anaesthesia. These studies compared an α-2 agonist (either clonidine or dexmedetomidine) with a control. The doses, methods, and time that the drugs were given varied between studies. All studies reported results for shivering. Our analysis showed that α-2 agonists significantly reduce the risk of postoperative shivering when administered before or during surgery. However, our analysis also showed that there were significant differences between studies that we could not explain. Some study authors had also presented results for core temperature, length of stay in the recovery room, and clinical side effects of the drugs. Seven studies reported that participants given dexmedetomidine were more likely to have a higher level of sedation after surgery, and five studies reported that participants given dexmedetomidine were more likely to have bradycardia (slower heart rate). We did not combine these results in an analysis. None of the studies presented patient-reported outcomes. We felt that the quality of the evidence was low and that some authors did not make enough of an effort to reduce the risk of bias in the methods, which could affect their results. For example, not all authors masked the anaesthetist or surgeon to which drug was given to each participant. This, along with some unexplained differences between studies and some concern about whether we could have missed some relevant results that had not been published, led us to assess the quality of the evidence for shivering as very low. We used GRADEpro software to assess evidence quality. Alpha-2 agonists may reduce the number of people who shiver after surgical procedures, but they are likely to make people sleepier as a side effect. However, the evidence is from studies of very low quality.

10.1002/14651858.CD011107.pub2

cochrane-simplification-train-1016

cochrane-simplification-train-1016

Four studies met the inclusion criteria (715 pregnant women), and reported on at least one of the outcomes of interest. We performed no meta-analyses as the interventions and outcomes measured in the studies were not sufficiently similar. For most outcomes there were no significant differences between groups; and results relating to abstaining or reducing alcohol consumption were mixed. Results from individual studies suggest that interventions may encourage women to abstain from alcohol in pregnancy. There was very little information provided on the effects of interventions on the health of mothers and babies. The evidence from the limited number of studies suggests that psychological and educational interventions may result in increased abstinence from alcohol, and a reduction in alcohol consumption among pregnant women. However, results were not consistent, and the paucity of studies, the number of total participants, the high risk of bias of some of the studies, and the complexity of interventions limits our ability to determine the type of intervention which would be most effective in increasing abstinence from, or reducing the consumption of, alcohol among pregnant women.

Four randomized controlled studies were included in the review; individual studies suggest that educational and counselling interventions may encourage women to abstain from alcohol or reduce the amount of alcohol they drink in pregnancy. The studies involved women who were less than 28 weeks pregnant who were consuming some alcohol. All were carried out in the USA. The interventions ranged from a 10-minute education session and provision of a self-help manual through to an hour-long motivational interview with reinforcement at each prenatal visit. Women in the control groups generally received routine care, which may have included advice on reducing alcohol intake. Outcomes were measured in different ways, and so results have been presented separately for each study. The studies provided very limited information on the effects of interventions on the health of women and their babies. There was very little information provided in these studies on the effects of interventions on the health of mothers and babies. There is an urgent need for more information in this area.

10.1002/14651858.CD004228.pub2

cochrane-simplification-train-1017

cochrane-simplification-train-1017

As of 2013, the review includes 29 studies describing nine possible chemoprotective agents, as well as description of two published meta-analyses. Among these trials, there were sufficient data in some instances to combine the results from different studies, most often using data from secondary non-quantitative measures. Nine of the studies were newly included at this update. Few of the included studies were at a high risk of bias overall, although often there was too little information to make an assessment. At least two review authors performed a formal review of an additional 44 articles but we did not include them in the final review for a variety of reasons. Of seven eligible amifostine trials (743 participants in total), one used quantitative sensory testing (vibration perception threshold) and demonstrated a favourable outcome in terms of amifostine neuroprotection, but the vibration perception threshold result was based on data from only 14 participants receiving amifostine who completed the post-treatment evaluation and should be regarded with caution. Furthermore the change measured was subclinical. None of the three eligible Ca/Mg trials (or four trials if a single retrospective study was included) described our primary outcome measures. The four Ca/Mg trials included a total of 886 participants. Of the seven eligible glutathione trials (387 participants), one used quantitative sensory testing but reported only qualitative analyses. Four eligible Org 2766 trials (311 participants) employed quantitative sensory testing but reported disparate results; meta-analyses of three of these trials using comparable measures showed no significant vibration perception threshold neuroprotection. The remaining trial reported only descriptive analyses. Similarly, none of the three eligible vitamin E trials (246 participants) reported quantitative sensory testing. The eligible single trials involving acetylcysteine (14 participants), diethyldithiocarbamate (195 participants), oxcarbazepine (32 participants), and retinoic acid (92 participants) did not perform quantitative sensory testing. In all, this review includes data from 2906 participants. However, only seven trials reported data for the primary outcome measure of this review, (quantitative sensory testing) and only nine trials reported our objective secondary measure, nerve conduction test results. Additionally, methodological heterogeneity precluded pooling of the results in most cases. Nonetheless, a larger number of trials reported the results of secondary (non-quantitative and subjective) measures such as the National Cancer Institute Common Toxicity Criteria (NCI-CTC) for neuropathy (15 trials), and these results we pooled and reported as meta-analysis. Amifostine showed a significantly reduced risk of developing neurotoxicity NCI-CTC (or equivalent) ≥ 2 compared to placebo (RR 0.26, 95% CI 0.11 to 0.61). Glutathione was also efficacious with an RR of 0.29 (95% CI 0.10 to 0.85). In three vitamin E studies subjective measures not suitable for combination in meta analysis each favoured vitamin E. For other interventions the qualitative toxicity measures were either negative (N-acetyl cysteine, Ca/Mg, DDTC and retinoic acid) or not evaluated (oxcarbazepine and Org 2766). Adverse events were infrequent or not reported for most interventions. Amifostine was associated with transient hypotension in 8% to 62% of participants, retinoic acid with hypocalcaemia in 11%, and approximately 20% of participantss withdrew from treatment with DDTC because of toxicity. At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxcarbazepine, retinoic acid, or vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients, as determined using quantitative, objective measures of neuropathy. Amifostine, calcium and magnesium, glutathione, and vitamin E showed modest but promising (borderline statistically significant) results favouring their ability to reduce the neurotoxicity of cisplatin and related chemotherapies, as measured using secondary, non-quantitative and subjective measures such as the NCI-CTC neuropathy grading scale. Among these interventions, the efficacy of only vitamin E was evaluated using quantitative nerve conduction studies; the results were negative and did not support the positive findings based on the qualitative measures. In summary, the present studies are limited by the small number of participants receiving any particular agent, a lack of objective measures of neuropathy, and differing results among similar trials, which make it impossible to conclude that any of the neuroprotective agents tested prevent or limit the neurotoxicity of platinum drugs.

We carried out a wide search for studies of treatments to prevent this type of nerve damage. We identified a total of 29 clinical trials, which involved almost 3000 participants who were receiving platinum-containing anticancer drugs (mostly cisplatin, oxaliplatin and carboplatin) for various types of cancer (mainly colon, ovary, and lung cancers). The nine treatments studied were: amifostine (seven trials), calcium and magnesium (four trials), glutathione (seven trials), Org 2766 (four trials) and vitamin E (three trials). There was one trial each of acetylcysteine, diethyldithiocarbamate (DDTC), oxcarbazepine, and retinoic acid. We chose an objective clinical test of sensation to report as our preferred measure of the effects of treatment. Only seven of the studies used this measure. Nine reported the results of nerve conduction studies which are another objective measure of nerve function. Most of the studies used a subjective assessment of neuropathy, such as the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy grading scale. Most of the included studies were fairly well performed, where it was possible to obtain this information. Based on the combined results that generally described secondary and non-quantitative measures such as the NCI-CTC neuropathy grading scale, modest but promising (borderline statistically significant) results favoured the use of amifostine, calcium and magnesium, and glutathione to reduce the neurotoxicity of cisplatin and related chemotherapies. Three studies of vitamin E could only be studied individually but the results of each imply some mild subjective benefits. Nevertheless, given the limitations of the studies, such as small numbers of participants, lack of objective measures of neuropathy, and differing results among similar trials, the data remain insufficient to conclude that any of the neuroprotective agents tested prevent or limit the neurotoxicity of platinum drugs. Most of the treatments were not associated with adverse events. Amifostine infusions were associated with temporary low blood pressure in a significant number of cases, and retinoic acid with low levels of calcium in the blood. About one-fifth of people treated with DDTC stopped taking it because of harmful effects. Amifostine, calcium and magnesium, vitamin E, and glutathione require further well designed trials to clarify if they are effective or not. This is an updated review. The evidence is current to 4 March 2013.

10.1002/14651858.CD005228.pub4

cochrane-simplification-train-1018

cochrane-simplification-train-1018

A total of four high-quality RCTs and six low-quality RCTs met the search criteria of this review. These studies included a total of 733 participants. Investigators compared three different posterior decompression techniques versus conventional laminectomy. Three studies (173 participants) compared unilateral laminotomy for bilateral decompression versus conventional laminectomy. Four studies (382 participants) compared bilateral laminotomy versus conventional laminectomy (one study included three treatment groups and compared unilateral and bilateral laminotomy vs conventional laminectomy). Finally, four studies (218 participants) compared a split-spinous process laminotomy versus conventional laminectomy. Evidence of low or very low quality suggests that different techniques of posterior decompression and conventional laminectomy have similar effects on functional disability and leg pain. Only perceived recovery at final follow-up was better in people who underwent bilateral laminotomy compared with conventional laminectomy (two RCTs, 223 participants, odds ratio 5.69, 95% confidence interval (CI) 2.55 to 12.71). Among the secondary outcome measures, unilateral laminotomy for bilateral decompression and bilateral laminotomy resulted in numerically fewer cases of iatrogenic instability, although in both cases, the incidence of instability was low (three RCTs, 166 participants, odds ratio 0.28, 95% CI 0.07 to 1.15; three RCTs, 294 participants, odds ratio 0.10, 95% CI 0.02 to 0.55, respectively). The difference in severity of postoperative low back pain following bilateral laminotomy (two RCTs, 223 participants, mean difference -0.51, 95% CI -0.80 to -0.23) and split-spinous process laminotomy compared with conventional laminectomy (two RCTs, 97 participants, mean difference -1.07, 95% CI -2.15 to -0.00) was significantly less, but was too small to be clinically important. A quantitative comparison between unilateral laminotomy and conventional laminectomy was not possible because of different reporting of outcome measures. We found no evidence to show that the incidence of complications, length of the procedure, length of hospital stay and postoperative walking distance differed between techniques of posterior decompression. The evidence provided by this systematic review for the effects of unilateral laminotomy for bilateral decompression, bilateral laminotomy and split-spinous process laminotomy compared with conventional laminectomy on functional disability, perceived recovery and leg pain is of low or very low quality. Therefore, further research is necessary to establish whether these techniques provide a safe and effective alternative for conventional laminectomy. Proposed advantages of these techniques regarding the incidence of iatrogenic instability and postoperative back pain are plausible, but definitive conclusions are limited by poor methodology and poor reporting of outcome measures among included studies. Future research is necessary to establish the incidence of iatrogenic instability using standardised definitions of radiological and clinical instability at comparable follow-up intervals. Long-term results with these techniques are currently lacking.

This review comprises published research studies current through June 2014. A total of 10 randomised controlled trials (RCTs), or studies comparing one treatment to another, were included in the final analysis. In total, the included studies looked at 733 participants. In this review, review authors compared conventional laminectomy versus three other surgical techniques for low back stenosis. Here's the breakdown: Three studies - involving a total of 173 patients - compared conventional laminectomy with one-sided laminotomy. Four studies - involving 382 patients total - compared conventional laminectomy with two-sided laminotomy (one study included three treatment groups and compared conventional laminectomy with one-sided and two-sided laminotomy). And finally, four studies - involving 218 patients total - compared conventional laminectomy with a split-spinous process laminotomy. The Cochrane review authors did not receive outside funding. This review found that each of the three newer techniques of surgery for low back stenosis delivered results no different from those of conventional laminectomy regarding self-care abilities and leg pain. Only perceived recovery of symptoms favoured patients who underwent bilateral laminotomy compared with conventional laminectomy, but the difference between unilateral laminotomy and split-spinous process laminotomy was not significant. The quality of evidence was low or very low according to Grades of Recommendation, Assessment, Development and Evaluation (GRADE) recommendations. This was due to the limited number of studies available for review and to poor study designs. Included studies were not designed in such a way as to yield reliable information about surgical outcomes. Before high-quality, evidence-based recommendations can be made about techniques of decompression for lumbar spinal stenosis, more rigorous studies should be done.

10.1002/14651858.CD010036.pub2

cochrane-simplification-train-1019

cochrane-simplification-train-1019

We did not identify any new trials from the updated search so the results remain unchanged as follows. We have included 10 studies describing two dosages of paracetamol. Of these, five studies (526 women) assessed 500 mg to 650 mg and six studies (841 women) assessed 1000 mg of paracetamol. We chose to use random-effects meta-analyses because of the heterogeneity in dosage used. Studies were from the 1970s to the early 1990s, and there was insufficient information to assess the risk of bias adequately, hence the findings need to be interpreted within this context. More women experienced pain relief with paracetamol compared with placebo (average risk ratio (RR) 2.14, 95% confidence interval (CI) 1.59 to 2.89, 10 studies, 1279 women). In addition, there were significantly fewer women having additional pain relief with paracetamol compared with placebo (RR 0.34, 95% CI 0.21 to 0.55, eight studies, 1132 women). Both the 500 mg to 650 mg and 1000 mg doses were effective in providing more pain relief than placebo. Maternal and neonatal potential adverse drug effects were not assessed in any of the included studies. Indeed few secondary outcomes were assessed. More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.

However, this review is part of a series of reviews looking at drugs to help relieve perineal pain once it is there in the early days after the birth. This review identified 10 studies, involving 1367 women, looking at how effective paracetamol might be in helping with this pain. The studies were quite old and thus not of high quality. However, they showed that paracetamol (either in a single 500 mg to 600 mg or a single 1000 mg dose) was effective at reducing the perineal pain, mostly caused by episiotomies. The studies did not look carefully at potential adverse effects but generally paracetamol at these doses causes few problems. There are also generally no identified problems for breastfed babies when mothers take paracetamol, but these outcomes were not specifically assessed in any of the included studies. The comparison of how effective paracetamol is compared with other drugs is being assessed in the other reviews in the series.

10.1002/14651858.CD008407.pub2

cochrane-simplification-train-1020

cochrane-simplification-train-1020

We included 10 studies with a total of 1066 infants. All studies were conducted during early childhood immunisation. As the breastfeeding intervention cannot be blinded, we rated all studies as being at high risk of bias for blinding of participants and personnel. We assessed nine studies as being at low risk of bias for incomplete outcome data. In addition, we rated nine studies as high risk for blinding of outcome assessment. We scored risk of bias related to random sequence generation, allocation concealment, and selective reporting as unclear for the majority of the studies due to lack of information. Our primary outcome was pain. Breastfeeding reduced behavioural pain responses (cry time and pain scores) during vaccination compared to no treatment, oral water, and other interventions such as cuddling, oral glucose, topical anaesthetic, massage, and vapocoolant. Breastfeeding did not consistently reduce changes in physiological indicators, such as heart rate. We pooled data for duration of cry from six studies (n = 547 infants). Breastfeeding compared to water or no treatment resulted in a 38-second reduction in cry time (MD -38, 95% CI -50 to -26; P < 0.00001). The quality of the evidence according to GRADE for this outcome was moderate, as most infants were 6 months or younger, and outcomes may be different for infants during their 12-month immunisation. We pooled data for pain scores from five studies (n = 310 infants). Breastfeeding was associated with a 1.7-point reduction in standardised pain scores (SMD -1.7, 95% CI -2.2 to -1.3); we considered this evidence to be of moderate quality as data were primarily from infants younger than 6 months of age. We could pool heart rate data following injections for only two studies (n = 186); we considered this evidence to be of low quality due to insufficient data. There were no differences between breastfeeding and control (MD -3.6, -23 to 16). Four of the 10 studies had more than two study arms. Breastfeeding was more effective in reducing crying duration or pain scores during vaccination compared to: 25% dextrose and topical anaesthetic cream (EMLA), vapocoolant, maternal cuddling, and massage. No included studies reported adverse events. We conclude, based on the 10 studies included in this review, that breastfeeding may help reduce pain during vaccination for infants beyond the neonatal period. Breastfeeding consistently reduced behavioural responses of cry duration and composite pain scores during and following vaccinations. However, there was no evidence that breastfeeding had an effect on physiological responses. No studies included in this review involved populations of hospitalised infants undergoing other skin-breaking procedures. Although it may be possible to extrapolate the review results to this population, further studies of efficacy, feasibility, and acceptability in this population are warranted.

In February 2016 we searched the medical literature for studies examining the effectiveness of breastfeeding babies 1 to 12 months old during the use of needles. We compared effectiveness of breastfeeding in reducing pain (as scored by crying time and pain scores), to holding, babies lying flat, or the giving of water or sweet solutions. We found 10 studies with a total of 1066 infants. All studies examined if breastfeeding reduced pain during vaccinations. Breastfeeding reduced crying in young babies having vaccinations. On average, breastfed babies cried for 38 seconds less than babies who were not breastfed (6 studies; 547 infants; moderate-quality evidence), and pain scores were significantly lower (5 studies; 310 infants; moderate-quality evidence). No studies reported on any harm (very low-quality evidence). We could draw no conclusions on risk of harm while breastfeeding healthy babies during vaccination. Going forward: if mothers are breastfeeding, it could be considered when possible for babies during vaccinations. More evidence is needed to learn if breastfeeding helps older babies and babies in hospital during blood work or procedures such as insertion of drips. The quality of the evidence was moderate for crying time and pain scores. Most studies included younger infants aged 1 to 6 months. Further research including older infants up to 12 months of age may change our conclusions. In addition, the studies evaluated the effects of breastfeeding during vaccination. We do not know whether breastfeeding helps sick babies aged 1 to 12 months in hospital during blood sampling or drip insertion.

10.1002/14651858.CD011248.pub2

cochrane-simplification-train-1021

cochrane-simplification-train-1021

We included 18 trials (421 participants; 3817 endoscopic procedures). We judged three trials as at low risk of bias. Ten trials compared VR training with no training, five trials with conventional endoscopy training, one trial with another form of endoscopy simulation training, and two trials compared two different methods of VR training. Due to substantial clinical and methodological heterogeneity across our four comparisons, we did not perform a meta-analysis for several outcomes. We rated the quality of evidence as moderate, low, or very low due to risk of bias, imprecision, and heterogeneity. Virtual reality endoscopy simulation training versus no training: There was insufficient evidence to determine the effect on composite score of competency (MD 3.10, 95% CI -0.16 to 6.36; 1 trial, 24 procedures; low-quality evidence). Composite score of competency was based on 5-point Likert scales assessing seven domains: atraumatic technique, colonoscope advancement, use of instrument controls, flow of procedure, use of assistants, knowledge of specific procedure, and overall performance. Scoring range was from 7 to 35, a higher score representing a higher level of competence. Virtual reality training compared to no training likely provides participants with some benefit, as measured by independent procedure completion (RR 1.62, 95% CI 1.15 to 2.26; 6 trials, 815 procedures; moderate-quality evidence). We evaluated overall rating of performance (MD 0.45, 95% CI 0.15 to 0.75; 1 trial, 18 procedures), visualisation of mucosa (MD 0.60, 95% CI 0.20 to 1.00; 1 trial, 55 procedures), performance time (MD -0.20 minutes, 95% CI -0.71 to 0.30; 2 trials, 29 procedures), and patient discomfort (SMD -0.16, 95% CI -0.68 to 0.35; 2 trials, 145 procedures), all with very low-quality evidence. No trials reported procedure-related complications or critical flaws (e.g. bleeding, luminal perforation) (3 trials, 550 procedures; moderate-quality evidence). Virtual reality endoscopy simulation training versus conventional patient-based training: One trial reported composite score of competency but did not provide sufficient data for quantitative analysis. Virtual reality training compared to conventional patient-based training resulted in fewer independent procedure completions (RR 0.45, 95% CI 0.27 to 0.74; 2 trials, 174 procedures; low-quality evidence). We evaluated performance time (SMD 0.12, 95% CI -0.55 to 0.80; 2 trials, 34 procedures), overall rating of performance (MD -0.90, 95% CI -4.40 to 2.60; 1 trial, 16 procedures), and visualisation of mucosa (MD 0.0, 95% CI -6.02 to 6.02; 1 trial, 18 procedures), all with very low-quality evidence. Virtual reality training in combination with conventional training appears to be advantageous over VR training alone. No trials reported any procedure-related complications or critical flaws (3 trials, 72 procedures; very low-quality evidence). Virtual reality endoscopy simulation training versus another form of endoscopy simulation: Based on one study, there were no differences between groups with respect to composite score of competency, performance time, and visualisation of mucosa. Virtual reality training in combination with another form of endoscopy simulation training did not appear to confer any benefit compared to VR training alone. Two methods of virtual reality training: Based on one study, a structured VR simulation-based training curriculum compared to self regulated learning on a VR simulator appears to provide benefit with respect to a composite score evaluating competency. Based on another study, a progressive-learning curriculum that sequentially increases task difficulty provides benefit with respect to a composite score of competency over the structured VR training curriculum. VR simulation-based training can be used to supplement early conventional endoscopy training for health professions trainees with limited or no prior endoscopic experience. However, we found insufficient evidence to advise for or against the use of VR simulation-based training as a replacement for early conventional endoscopy training. The quality of the current evidence was low due to inadequate randomisation, allocation concealment, and/or blinding of outcome assessment in several trials. Further trials are needed that are at low risk of bias, utilise outcome measures with strong evidence of validity and reliability, and examine the optimal nature and duration of training.

We included 18 trials with 421 participants and 3817 endoscopy procedures. Ten trials compared virtual reality training with no training; five compared virtual reality training with patient-based endoscopy training; one compared virtual reality training with another form of endoscopy simulation training; and two compared two different methods of virtual reality training. Ten trials studied colonoscopy, three studied sigmoidoscopy, and five studied oesophagogastroduodenoscopy. Participants included medical trainees with limited or no endoscopy training from gastroenterology, medicine, family medicine, or general surgery, along with nurses. Compared to no training, virtual reality training appears to provide trainees with an advantage as measured by the ability to complete procedures independently, overall rating of performance, and visualisation of the colon or oesophagus. We found no conclusive evidence that virtual reality training, as compared with traditional patient-based training or another method of endoscopy simulation training, provided benefit, although data were limited. Existing virtual reality simulation curricula can be improved by applying educational theory such as a progressive learning strategy, whereby trainees complete increasingly difficult cases. The results of this review have shown that virtual reality endoscopy training can be used to supplement early traditional endoscopy training for trainees with limited or no endoscopic experience. Overall, the quality of the evidence was poor based on potential bias due to poor methodological reporting in trials and imprecision due to few participants and endoscopic procedures. Future studies must adhere to quality standards, such as proper randomisation, along with using valid metrics to measure endoscopic performance. Researchers should also compare the effectiveness of different simulation curricula that are based on educational theories.

10.1002/14651858.CD008237.pub3

cochrane-simplification-train-1022

cochrane-simplification-train-1022

The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50). Amisulpride induced less weight gain than risperidone (n=585, 3 RCTs, MD -0.99 CI -1.61 to -0.37) or olanzapine (n=671, 3 RCTs, MD -2.11 CI -2.94 to -1.29). Olanzapine was also associated with a higher increase of glucose (n=406, 2 RCTs, MD -7.30 CI -7.62 to -6.99). There was no difference in terms of cardiac effects and extra pyramidal symptoms (EPS) compared with olanzapine (akathisia: n= 587, 2 RCTs, RR 0.66 CI 0.36 to 1.21), compared with risperidone (akathisia: n=586, 3 RCTs, RR 0.80 CI 0.58 to 1.11) and compared with ziprasidone (akathisia: n=123, 1 RCT, RR 0.63, CI 0.11 to 3.67). There is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions. Note: the 47 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.

This review compared the effects of amisulpride with those of other so called second generation (atypical) antipsychotic drugs. For half of the possible comparisons not a single relevant study could be identified. Based on very limited data there was no difference in efficacy comparing amisulpride with olanzapine and risperidone, but a certain advantage compared with ziprasidone. Amisulpride was associated with less weight gain than risperidone and olanzapine.

10.1002/14651858.CD006624.pub2

cochrane-simplification-train-1023

cochrane-simplification-train-1023

Three trials were identified in this review as satisfying inclusion criteria. Results of all three trials were evaluated, however, one of these trials had compromised methodological quality and, therefore the focus was placed on the other two trials. Data were not pooled due to the heterogeneity between trials. The first trial (n = 24) showed a benefit of cognitive behavioural therapy (CBT) in people with mild TBI and acute stress disorder. Fewer people receiving CBT had diagnosis of post-traumatic stress disorder (PTSD) at post-treatment compared to the control supportive counselling group, with maintenance of treatment gains found at six-month follow up. The second trial (n = 20) showed that post-treatment anxiety symptomatology of people with mild to moderate TBI was lower in the combined CBT and neurorehabilitation group compared to the no intervention control group. This review provides some evidence for the effectiveness of CBT for treatment of acute stress disorder following mild TBI and CBT combined with neurorehabilitation for targeting general anxiety symptomatology in people with mild to moderate TBI. These findings need to be viewed in light of the small number, small sample size and heterogeneous characteristics of current trials published in this area. More trials focusing on comparable psychological interventions, severity of injury of participants and diagnosis of anxiety disorder(s) are needed.

This review identified three randomised controlled trials in the area of psychological treatments for anxiety after TBI. Some evidence was found for the effectiveness of the following interventions: cognitive behavioural therapy (CBT) for treatment of acute stress disorder following mild TBI, and combining CBT and neurorehabilitation for treatment of general anxiety symptoms in people with mild to moderate TBI. The ability to make strong conclusions on the effectiveness of these approaches is limited by the small number of trials available for pooling of data, especially trials with similar conditions and participants.

10.1002/14651858.CD005239.pub2

cochrane-simplification-train-1024

cochrane-simplification-train-1024

There were no data comparing best supportive care with chemotherapy. Cisplatin-based regimens are the most widely used and therefore we have concentrated on these trials. In terms of response rates some non-platinum regimens are equivalent but toxicity is higher. The most common cisplatin regimen was 50 mg/m2 day 1 q21days. Higher doses had similar survivals. There was no direct comparison between single-agent cisplatin and carboplatin. Overall survival (OS) and progression-free survival (PFS) were not adequately reported and quality of life (QoL) outcomes were incompletely documented. Combination regimens were more toxic than single agents, but in the limited reported data this did not appear to adversely affect QoL. No significant difference in response rate by site of recurrence was found, although there was a trend towards improved response when the main site of disease was beyond the previously irradiated pelvis. Combination cisplatin-based chemotherapy could be a viable option for patients of good performance status with recurrent/metastatic cervical cancer, but further trials that report adequate survival and QoL data are sought. Response rates and improvements in survival are low. Cisplatin-based combinations have significant toxicity. Outcomes are poor and novel cytotoxic/biological agents and optimal scheduling need further investigation. Future trials need to stratify for and perform planned subgroup analysis with respect to previous treatment and site of recurrence.

A literature search was conducted identifying 30 potential trials; four trials were excluded. The 26 clinical trials included in this review encompass a large range of different drugs, doses and combinations in a mixed group of patients over a long time period (1976 to 2011), making it difficult to compare treatment options. Although there are no trials directly comparing chemotherapy with symptomatic management alone, chemotherapy is widely used in this setting and assumed to be of benefit. Cisplatin and carboplatin chemotherapy were shown to shrink the cancer in 10% to 30% of patients and are widely used in current practice. Cisplatin chemotherapy when combined with other drugs has been shown to prolong survival by a few months compared with cisplatin alone, but with the cost of increased side effects. Other chemotherapy has been used, but has been found to be less effective or more toxic. Quality of life for patients on chemotherapy appears to be similar for cisplatin and cisplatin-based combinations. Nearly all patients in these studies were relatively fit and well prior to starting treatment, despite their cancer; these results may not be the same in patients who are not fit and well.

10.1002/14651858.CD006469.pub2

cochrane-simplification-train-1025

cochrane-simplification-train-1025

We did not find any studies fulfilling the inclusion criteria, therefore no outcome data are reported. We identified nine studies after initial screening and, after further evaluation, we excluded these. The excluded studies involved a total of 163 individuals aged two years to 18 years. We excluded studies for three main reasons: they were non-randomized or case series studies, they were studies of people over 18 years of age or even where the study was randomised, the study population was mixed and results pertaining to the visually impaired cohort could not be independently evaluated. No significant adverse effects of melatonin were reported in these excluded studies. There is currently no high quality data to support or refute the use of melatonin for sleep disorders in visually impaired children. Placebo-controlled trials examining important clinical outcomes such as sleep quality, sleep latency, duration of sleep and night-time awakenings are needed. As the numbers of children meeting study inclusion criteria are likely to be low at individual sites, multicentre collaboration between developmental paediatricians, sleep physicians and other health care professionals is essential to achieve sufficient sample size for controlled studies. Such collaboration would help facilitate local recruitment at multiple sites, with study oversight being provided by paediatricians with expertise in sleep disorders. Participation of collaborators with experience in evidence-based practice research is also desirable due to the lack of protocols on melatonin therapy in the target population.

The current review planned to examine studies on the use of melatonin in these children to determine whether this drug is effective for improving their sleep (safety is not mentioned in objectives or abstract and adverse effects is a secondary outcome). We only wanted to use studies where the children had been randomly allocated to a treatment group and a control group that got no treatment or another medication or a placebo. We did not find any of these studies that were suitable to be included in our review and so we are unable to draw any conclusions about whether or not melatonin improves sleep for visually impaired children. To find out, we need appropriately designed clinical trials. Due to lack of knowledge about best practice in the use of melatonin with these children, it would be useful to have researchers involved who are experienced in sleep disorders and in evidence-based practice research. In addition, studies involving more than one location would be beneficial to increase the number of children being evaluated and make it more likely we will reach solid conclusions about whether melatonin works for this group of children, as well as details about the most effective dosage and timing of the treatment.

10.1002/14651858.CD008473.pub2

cochrane-simplification-train-1026

cochrane-simplification-train-1026

We identified 28 randomised trials including 8950 participants (newly incorporated in this update: 10 trials including 4227 participants). The overall quality of the evidence was generally low to moderate. Pooled estimates showed a reduction in thromboembolic events (RR 0.58, 95% CI 0.45 to 0.75; participants = 7594; studies = 18; moderate quality of evidence). Both, trials of self-management or self-monitoring showed reductions in thromboembolic events (RR 0.47, 95% CI 0.31 to 0.70; participants = 3497; studies = 11) and (RR 0.69, 95% CI 0.49 to 0.97; participants = 4097; studies = 7), respectively; the quality of evidence for both interventions was moderate. No reduction in all-cause mortality was found (RR 0.85, 95% CI 0.71 to 1.01; participants = 6358; studies = 11; moderate quality of evidence). While self-management caused a reduction in all-cause mortality (RR 0.55, 95% CI 0.36 to 0.84; participants = 3058; studies = 8); self-monitoring did not (RR 0.94, 95% CI 0.78 to 1.15; participants = 3300; studies = 3); the quality of evidence for both interventions was moderate. In 20 trials (8018 participants) self-monitoring or self-management did not reduce major haemorrhage (RR 0.95, 95% CI, 0.80 to 1.12; moderate quality of evidence). There was no significant difference found for minor haemorrhage (RR 0.97, 95% CI 0.67 to 1.41; participants = 5365; studies = 13). The quality of evidence was graded as low because of serious risk of bias and substantial heterogeneity (I2 = 82%). Participants who self-monitor or self-manage can improve the quality of their oral anticoagulation therapy. Thromboembolic events were reduced, for both those self-monitoring or self-managing oral anticoagulation therapy. A reduction in all-cause mortality was observed in trials of self-management but not in self-monitoring, with no effects on major haemorrhage.

This is an update of the original review published in 2010. We performed a new search and found 10 new studies (with 4227 participants) to add to the original review, which changed some of the findings. In total, we found 28 randomised trials including 8950 participants that compared self-monitoring and self-management with standard monitoring. The quality of the evidence was generally low to moderate. The combined results of the 28 trials showed a halving of thromboembolic events with self-monitoring and self-management and no reduction in the number of major bleeds. Self-management had similar reductions in thromboembolic events and mortality to the overall benefit, with no effect on major bleeds. Self-monitoring halved the number of major haemorrhages that occurred but did not significantly reduce the rates of thrombotic events or all-cause mortality. In conclusion, self-monitoring or self-management can improve the quality of oral anticoagulant therapy, leading to fewer thromboembolic events and lower mortality, without a reduction in the number of major bleeds. Self-monitoring and self-management are not feasible for all patients, which requires the identification and education of suitable patients.

10.1002/14651858.CD003839.pub3

cochrane-simplification-train-1027

cochrane-simplification-train-1027

Our search identified a total of 8124 records, from which we included 17 studies (54 papers) with 23,200 children in the review. The included studies reported on one or more of the pre-specified primary outcomes, and five studies included multiple comparison groups. Overall, the majority of trials were at low risk of bias for random sequence generation, allocation concealment, blinding of outcome assessment, incomplete outcome data, selective reporting and other sources of bias, but at high risk of bias for blinding of participants and personnel due to the nature of the intervention. Using the GRADE approach, we judged the quality of the evidence for most outcomes as low or moderate. LNS+complementary feeding compared with no intervention Thirteen studies compared LNS plus complementary feeding with no intervention. LNS plus complementary feeding reduced the prevalence of moderate stunting by 7% (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.88 to 0.98; nine studies, 13,372 participants; moderate-quality evidence), severe stunting by 15% (RR 0.85, 95% CI 0.74 to 0.98; five studies, 6151 participants; moderate-quality evidence), moderate wasting by 18% (RR 0.82, 95% CI 0.74 to 0.91; eight studies; 13,172 participants; moderate-quality evidence), moderate underweight by 15% (RR 0.85, 95% CI 0.80 to 0.91; eight studies, 13,073 participants; moderate-quality evidence), and anaemia by 21% (RR 0.79, 95% CI 0.69 to 0.90; five studies, 2332 participants; low-quality evidence). There was no impact of LNS plus complementary feeding on severe wasting (RR 1.27, 95% CI 0.66 to 2.46; three studies, 2329 participants) and severe underweight (RR 0.78, 95%CI 0.54 to 1.13; two studies, 1729 participants). Adverse effects did not differ between the groups (RR 0.86, 95% CI 0.74 to 1.01; three studies, 3382 participants). LNS+complementary feeding compared with FBF Five studies compared LNS plus complementary feeding with other FBF, including corn soy blend and UNIMIX. We pooled four of the five studies in meta-analyses and found that, when compared to other FBF, LNS plus complementary feeding significantly reduced the prevalence of moderate stunting (RR 0.89, 95% CI 0.82 to 0.97; three studies, 2828 participants; moderate-quality evidence), moderate wasting (RR 0.79, 95% CI 0.65 to 0.97; two studies, 2290 participants; moderate-quality evidence), and moderate underweight (RR 0.81, 95% CI 0.73 to 0.91; two studies, 2280 participants; moderate-quality evidence). We found no difference between LNS plus complementary feeding and FBF for severe stunting (RR 0.41, 95% CI 0.12 to 1.42; two studies, 729 participants; low-quality evidence), severe wasting (RR 0.64, 95% CI 0.19 to 2.81; two studies, 735 participants; moderate-quality evidence), and severe underweight (RR 1.23, 95% CI 0.67 to 2.25; one study, 173 participants; low-quality evidence). LNS+complementary feeding compared with MNP Four studies compared LNS plus complementary feeding with MNP. We pooled data from three of the four studies in meta-analyses and found that compared to MNP, LNS plus complementary feeding significantly reduced the prevalence of moderate underweight (RR 0.88, 95% CI 0.78 to 0.99; two studies, 2004 participants; moderate-quality evidence) and anaemia (RR 0.38, 95% CI 0.21 to 0.68; two studies, 557 participants; low-quality evidence). There was no difference between LNS plus complementary feeding and MNP for moderate stunting (RR 0.92, 95% CI 0.82 to 1.02; three studies, 2365 participants) and moderate wasting (RR 0.97, 95% CI 0.77 to 1.23; two studies, 2004 participants). The findings of this review suggest that LNS plus complementary feeding compared to no intervention is effective at improving growth outcomes and anaemia without adverse effects among children aged six to 23 months in low- and middle-income countries (LMIC) in Asia and Africa, and more effective if provided over a longer duration of time (over 12 months). Limited evidence also suggests that LNS plus complementary feeding is more effective than FBF and MNP at improving growth outcomes.

This review includes 17 studies (from 54 reports) with 23,200 children. Four of the included studies were conducted in Malawi, three in Bangladesh, two in Ghana and one each in Burkina Faso, Haiti, Honduras, Chad, Congo, Kenya, Niger, Peru, Guatemala, and Indonesia. Four included studies enrolled pregnant women and provided LNS plus complementary feeding during pregnancy and post-partum, followed by infant supplementation starting at six months of age. The other studies provided LNS plus complementary feeding to children after six months of age. None of the included studies were conducted in emergency settings. Findings of this review suggest that LNS plus complementary feeding is probably an effective intervention for improving growth outcomes and reducing the occurrence of children who are of short stature for their age (stunting), have low weight for their age (moderate underweight), have low weight for their height (moderate wasting) and anaemia. Additionally, LNS plus complementary feeding probably improves height and weight for age as well as mid-upper arm circumference without adverse effects among children aged six to 23 months. The intervention seems to be more effective if provided for a duration longer than 12 months. Evidence also suggests that LNS plus complementary probably reduces moderate stunting, moderate wasting and moderate underweight, compared to other FBF. Furthermore, LNS plus complementary feeding is probably more effective than MNP at reducing moderate underweight and improving height and weight. Overall, we considered most studies to be at high risk of bias for blinding of participants and personnel due to the nature of intervention. We rated the quality of the evidence for most outcomes as either low or moderate. The evidence is current to October 2018.

10.1002/14651858.CD012611.pub3

cochrane-simplification-train-1028

cochrane-simplification-train-1028

Twenty-six randomized clinical trials fulfilled entry criteria. No study assessed combined long-term morbidity. Routine vitamin E supplementation significantly increased hemoglobin concentration by a small amount. Vitamin E significantly reduced the risk of germinal matrix/intraventricular hemorrhage and increased the risk of sepsis; however, heterogeneity limits the strength of these latter two inferences. Vitamin E did not significantly affect other morbidity or mortality. In VLBW infants, vitamin E supplementation significantly increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Subgroup analyses demonstrated (1) an association between intravenous, high-dose vitamin E supplementation and increased risk of sepsis and of parenchymal cerebral hemorrhage; (2) an association between vitamin E supplementation by other than the intravenous route and reduced risk of germinal matrix-intraventricular hemorrhage and of severe intraventricular hemorrhage; and (3) an association between serum tocopherol levels greater than 3.5 mg/dl and increased risk of sepsis and reduced risk for severe retinopathy among those examined. Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants, vitamin E increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Evidence does not support the routine use of vitamin E supplementation by intravenous route at high doses or aiming at serum tocopherol levels greater than 3.5 mg/dl.

This review of studies of vitamin E supplements found that while extra vitamin E reduces the chances of some complications (including disease of the retina), the risk of life-threatening infection is increased. The risk of bleeding in the brain is increased when extra vitamin E is given by vein but decreased when the extra vitamin E is given by other routes.

10.1002/14651858.CD003665

cochrane-simplification-train-1029

cochrane-simplification-train-1029

We included eight trials involving 5701 patients. Six trials tested ancrod and two trials tested defibrase (patients were treated for less than three hours to less than 48 hours). Allocation concealment was adequate in seven trials. Fibrinogen depleting agents marginally reduced the proportion of patients who were dead or disabled at the end of follow-up (risk ratio (RR) 0.95, 95% confidence Interval (CI) 0.90 to 0.99, 2P = 0.02). There was no statistically significant difference in death from all causes during the scheduled treatment or follow-up period. There were fewer stroke recurrences in the treatment group than in the control group (RR 0.67, 95% CI 0.49 to 0.92, 2P = 0.01). However, symptomatic intracranial haemorrhage was about twice as common in the treatment group compared with the control group (RR 2.42, 95% CI 1.65 to 3.56, 2P < 0.00001). The current evidence is promising but not yet sufficiently robust to support the routine use of fibrinogen depleting agents for the treatment of acute ischaemic stroke. Further trials are needed to determine whether there is worthwhile benefit, and if so, which categories of patients are most likely to benefit.

Evidence from this updated review, which includes eight trials involving 5701 participants, indicates that there is currently not sufficient evidence to support the routine use of fibrinogen depleting agents for the treatment of acute ischaemic stroke. Further trials are needed to determine reliably whether there is worthwhile benefit, and if so, which categories of patients are most likely to benefit.

10.1002/14651858.CD000091.pub2

cochrane-simplification-train-1030

cochrane-simplification-train-1030

We included 11 trials that enrolled a total of 2412 pregnant women who smoked at enrolment, nine trials of NRT and two trials of bupropion as adjuncts to behavioural support, with comparable behavioural support provided in the control arms. No trials investigated varenicline or ECs. We assessed four trials as at low risk of bias overall. The overall certainty of the evidence was low across outcomes and comparisons as assessed using GRADE, with reductions in confidence due to risk of bias, imprecision, and inconsistency. Compared to placebo and non-placebo (behavioural support only) controls, there was low-certainty evidence that NRT increased the likelihood of smoking abstinence in later pregnancy (RR 1.37, 95% CI 1.08 to 1.74; I² = 34%, 9 studies, 2336 women). However, in subgroup analysis by comparator type, there was a subgroup difference between placebo-controlled and non-placebo controlled RCTs (test for subgroup differences P = 0.008). There was unclear evidence of an effect in placebo-controlled RCTs (RR 1.21, 95% CI 0.95 to 1.55; I² = 0%, 6 studies, 2063 women), whereas non-placebo-controlled trials showed clearer evidence of a benefit (RR 8.55, 95% CI 2.05 to 35.71; I² = 0%, 3 studies, 273 women). An additional subgroup analysis in which studies were grouped by the type of NRT used found no difference in the effectiveness of NRT in those using patches or fast-acting NRT (test for subgroup differences P = 0.08). There was no evidence of a difference between NRT and control groups in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care, caesarean section, congenital abnormalities, or neonatal death. In one study infants born to women who had been randomised to NRT had higher rates of 'survival without developmental impairment' at two years of age compared to the placebo group. Non-serious adverse effects observed with NRT included headache, nausea, and local reactions (e.g. skin irritation from patches or foul taste from gum), but data could not be pooled. Adherence to NRT treatment regimens was generally low. We identified low-certainty evidence that there was no difference in smoking abstinence rates observed in later pregnancy in women using bupropion when compared to placebo control (RR 0.74, 95% CI 0.21 to 2.64; I² = 0%, 2 studies, 76 women). Evidence investigating the safety outcomes of bupropion use was sparse, but the existing evidence showed no difference between the bupropion and control group. NRT used for smoking cessation in pregnancy may increase smoking cessation rates in late pregnancy. However, this evidence is of low certainty, as the effect was not evident when potentially biased, non-placebo-controlled RCTs were excluded from the analysis. Future studies may therefore change this conclusion. We found no evidence that NRT has either positive or negative impacts on birth outcomes; however, the evidence for some of these outcomes was also judged to be of low certainty due to imprecision and inconsistency. We found no evidence that bupropion may be an effective aid for smoking cessation during pregnancy, and there was little evidence evaluating its safety in this population. Further research evidence on the efficacy and safety of pharmacotherapy and EC use for smoking cessation in pregnancy is needed, ideally from placebo-controlled RCTs that achieve higher adherence rates and that monitor infants' outcomes into childhood. Future RCTs of NRT should investigate higher doses than those tested in the studies included in this review.

We searched for evidence on 20 May 2019 and identified 11 randomised studies (studies in which participants are assigned to one of two or more treatment groups using a random method) that enrolled a total of 2412 women. Nine studies tested NRT used alongside counselling to stop smoking, whilst the other two studies tested bupropion. Low-quality evidence suggests that NRT combined with behavioural support might help women to stop smoking in later pregnancy more than behavioural support alone. Medication trials often use placebos, that is tablets or patches that look like the drug but do not actually include it, so that each comparison group has equal expectation of success and there is a fairer test of the benefits of the medicine itself. When just the higher-quality, placebo-controlled trials were analysed, the evidence suggested that NRT was more effective than placebo NRT. There was no evidence that either nicotine patches or fast-acting NRT (such as gum or lozenge) was more effective than the other. Low-quality evidence suggests that bupropion may be no more effective than placebo in helping women quit smoking later in pregnancy. We found no trials investigating other smoking cessation pharmacotherapies or electronic cigarettes. There was insufficient evidence to conclude whether NRT had either positive or negative impacts on rates of miscarriage, stillbirth, preterm birth (less than 37 weeks), mean birthweight, low birthweight (less than 2500 g), admissions of babies to neonatal intensive care, or newborn deaths. However, in one trial where infants were followed until two years of age, those infants born to women who had been randomised to NRT were more likely to have healthy development. Similarly, it is unclear whether bupropion had a positive or negative impact on birth outcomes. Studies that looked at whether women used their stop smoking medications as instructed found that use was generally low, and the majority of women used little of the NRT they were given. More research evidence is needed, in particular placebo-controlled trials that test higher doses of NRT, encourage women to use sufficient medication, and follow infants into childhood. Furthermore, more studies are required investigating the effect and safety of bupropion, electronic cigarettes, and varenicline for giving up smoking during pregnancy.

10.1002/14651858.CD010078.pub3

cochrane-simplification-train-1031

cochrane-simplification-train-1031

The search yielded 7057 references of which we identified three RCTs for inclusion, four ongoing trials and one study awaiting classification. All three included RCTs compared videolaryngoscopy with direct laryngoscopy during intubation attempts by trainees. Time to intubation was similar between videolaryngoscopy and direct laryngoscopy (mean difference (MD) -0.62, 95% confidence interval (CI) -6.50 to 5.26; 2 studies; 311 intubations) (very low quality evidence). Videolaryngoscopy did not decrease the number of intubation attempts (MD -0.05, 95% CI -0.18 to 0.07; 2 studies; 427 intubations) (very low quality evidence). Moderate quality evidence suggested that videolaryngoscopy increased the success of intubation at first attempt (typical risk ratio (RR) 1.44, 95% CI 1.20 to 1.73; typical risk difference (RD) 0.19, 95% CI 0.10 to 0.28; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 10; 3 studies; 467 intubation attempts). Desaturation episodes during intubation attempts were similar between videolaryngoscopy and direct laryngoscopy (MD -0.76, 95% CI -5.74 to 4.23; 2 studies; 359 intubations) (low quality evidence). There was no difference in the incidence of airway trauma due to intubation attempts (RR 0.10, 95% CI 0.01 to 1.80; RD -0.04, 95% CI -0.09 to -0.00; 1 study; 213 intubations) (low quality evidence). There were no data available on other adverse effects of videolaryngoscopy. Moderate to very low quality evidence suggests that videolaryngoscopy increases the success of intubation in the first attempt but does not decrease the time to intubation or the number of attempts for intubation. However, these studies were conducted with trainees performing the intubations and these results highlight the potential usefulness of the videolaryngoscopy as a teaching tool. Well-designed, adequately powered RCTs are necessary to confirm efficacy and address safety and cost-effectiveness of videolaryngoscopy for endotracheal intubation in neonates by trainees and those proficient in direct laryngoscopy.

We sought evidence for the usefulness of these video-assisted devices for the placement of breathing tubes in babies. We searched scientific databases for clinical trials of babies who needed intubation in the delivery room, operating room or intensive care unit. The studies could measure time to intubation, number of attempts at intubation, success rate of first intubation or side effects. The evidence is current to May 2017. We included three studies, which provided data on up to 467 intubation attempts in newborns by trainees. Data from three included studies suggest that videolaryngoscopy increases the success of intubation at first attempt but does not decrease the time to intubation, the number of attempts or side effects due to placement of the breathing tube. These studies were done with trainees and highlights the use of videolaryngoscopy as a teaching tool. We make a case for further research in evaluating the use of video-assisted devices in the placement of breathing tubes in newborns.

10.1002/14651858.CD009975.pub3

cochrane-simplification-train-1032

cochrane-simplification-train-1032

We included four studies with a total of 115 patients randomised to undergo a vascular procedure with remote ischaemic preconditioning and 117 patients randomised to have the procedure without remote ischaemic preconditioning. None of the trials were of low risk of bias. There was no significant difference in mortality between the two groups (RR 1.70, 95% CI 0.51 to 5.72). Similarly, there was no statistically significant difference between the two groups for all other outcomes except reduced risk of myocardial infarction in the remote ischaemic preconditioning group, which was significant by the fixed-effect model (RR 0.31, 95% CI 0.10 to 0.90) but not by the random-effects model (RR 0.34, 95% CI 0.11 to 1.08). This positive effect was from the results of only one trial and was not consistently observed. Furthermore, it was noted that there was an observed trend of high incidence of unplanned critical care admission in the remote ischaemic preconditioning group, although this was not statistically significant (RR 2.15, 95% CI 0.87 to 5.33). Based on current evidence from small pilot trials, there are too few data to be able to say whether remote ischaemic preconditioning has any beneficial or harmful effects. The safety of this technique needs to be confirmed in adequately powered trials. Therefore, further randomised trials on this technique are required.

We performed a systematic search of the literature to identify all the randomised controlled trials conducted on this topic. A total of 232 patients in four trials were randomised to remote ischaemic preconditioning or no preconditioning for three different operations on blood vessels. Based on the evidence from these small trials, there were too few data to be able to say whether remote ischaemic preconditioning has any beneficial or harmful effects. The studies varied in the surgical procedures, outcome measures and the way remote ischaemia was induced. The number of deaths around the time of surgery was not clearly different between the two groups. Heart attacks (myocardial infarction) may have been reduced in the remote ischaemic preconditioning group but this was apparent in only one trial and was not consistent across the trials. Unplanned critical care admissions tended to increase in the remote ischaemic preconditioning group. All the trials had a high risk of bias and the safety of this technique needs to be confirmed in trials with adequate numbers of participants.

10.1002/14651858.CD008472.pub2

cochrane-simplification-train-1033

cochrane-simplification-train-1033

We included 13 studies involving 5810 participants from Latin America, Africa and Asia. We excluded 38 studies and identified six ongoing/unpublished trials. All trials compared the provision of MNP for point-of-use fortification with no intervention or placebo. No trials compared the effects of MNP versus iron-containing supplements (as drops, tablets or syrup). The sample sizes in the included trials ranged from 90 to 2193 participants. Six trials included participants younger than 59 months of age only, four included only children aged 60 months or older, and three trials included children both younger and older than 59 months of age. MNPs contained from two to 18 vitamins and minerals. The iron doses varied from 2.5 mg to 30 mg of elemental iron. Four trials reported giving 10 mg of elemental iron as sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), chelated ferrous sulphate or microencapsulated ferrous fumarate. Three trials gave 12.5 mg of elemental iron as microencapsulated ferrous fumarate. Three trials gave 2.5 mg or 2.86 mg of elemental iron as NaFeEDTA. One trial gave 30 mg and one trial provided 14 mg of elemental iron as microencapsulated ferrous fumarate, while one trial gave 28 mg of iron as ferrous glycine phosphate. In comparison with receiving no intervention or a placebo, children receiving iron-containing MNP for point-of-use fortification of foods had lower risk of anaemia prevalence ratio (PR) 0.66, 95% confidence interval (CI) 0.49 to 0.88, 10 trials, 2448 children; moderate-quality evidence) and iron deficiency (PR 0.35, 95% CI 0.27 to 0.47, 5 trials, 1364 children; moderate-quality evidence) and had higher haemoglobin (mean difference (MD) 3.37 g/L, 95% CI 0.94 to 5.80, 11 trials, 2746 children; low-quality evidence). Only one trial with 115 children reported on all-cause mortality (zero cases; low-quality evidence). There was no effect on diarrhoea (risk ratio (RR) 0.97, 95% CI 0.53 to 1.78, 2 trials, 366 children; low-quality evidence). Point-of-use fortification of foods with MNPs containing iron reduces anaemia and iron deficiency in preschool- and school-age children. However, information on mortality, morbidity, developmental outcomes and adverse effects is still scarce.

This review included 13 trials with 5810 participants from Latin America, Africa and Asia. All trials compared the provision of MNP for point-of-use fortification with no intervention or placebo. Six trials included participants younger than 59 months of age only, four included only children aged 60 months of age or older, and three trials included children both younger and older than 59 months of age. MNPs contained from two to 18 vitamins and minerals. We searched existing clinical trials in December 2016 and ongoing trials in April 2017. We also contacted relevant institutions for additional information upon publication of the protocol and in April 2017. The review found that children receiving iron-containing MNP for point-of-use fortification of foods were at significantly lower risk of having anaemia and iron deficiency and had higher haemoglobin concentrations. We did not find any positive or negative effect on diarrhoea or mortality, but the data on these two outcomes were very limited. We rated the overall quality of the evidence for the provision of multiple MNP versus no intervention or placebo as moderate for anaemia, iron deficiency and adverse effects. We judged the evidence to be of low quality for haemoglobin, mortality and diarrhoea, and to be very low-quality for ferritin. In general, the most common risk of bias in the studies was the lack of blinding for participants, personnel and outcome assessors. Point-of-use fortification of foods with MNPs containing iron reduces anaemia and iron deficiency in preschool- and school-age children and seems feasible for public health purposes. However, future research should aim to increase the body of evidence on mortality, morbidity, developmental outcomes and adverse effects. Due to the lack of trials, we were unable to determine at this time if this intervention has comparable effects to those observed with iron supplements (provided as drops, tablets or syrup).

10.1002/14651858.CD009666.pub2

cochrane-simplification-train-1034

cochrane-simplification-train-1034

We included six studies (involving 122 women) but only four studies (involving only 116 women) contributed data to the analyses. Infant There were very little data of relevance to the three main (primary) outcomes considered in this review: There was no significant difference between planned immediate caesarean section and planned vaginal delivery with respect to birth injury to infant (risk ratio (RR) 0.56, 95%, confidence interval (CI) 0.05 to 5.62; one trial, 38 women) or birth asphyxia (RR 1.63, 95% CI 0.84 to 3.14; one trial, 12 women). The only cases of birth trauma were a laceration of the buttock in a baby who was delivered by caesarean section and mild bruising in another allocated to the group delivered vaginally. The difference between the two groups with regard to perinatal deaths was not significant (0.29, 95% CI 0.07 to 1.14; three trials, 89 women) and there were no data specifically relating to neonatal admission to special care and/or intensive care unit. There was also no difference between the caesarean or vaginal delivery groups in terms of markers of possible birth asphyxia (RR 1.63, 95% CI 0.84 to 3.14; one trial, 12 women) or Apgar score less than seven at five minutes (RR 0.83, 95% CI 0.43 to 1.60; four trials, 115 women) and no difference in attempts at breastfeeding (RR 1.40, 95% 0.11 to 17.45; one trial, 12 women). There was also no difference in neonatal fitting/seizures (RR 0.22, 95% CI 0.01 to 4.32; three trials, 77 women), hypoxic ischaemic encephalopathy (RR 4.00, 95% CI 0.20 to 82.01;one trial, 12 women) or respiratory distress syndrome (RR 0.55, 95% CI 0.27 to 1.10; three trials, 103 women). There were no data reported in the trials specifically relating to meconium aspiration. There was also no significant difference between the two groups for abnormal follow-up in childhood (RR 0.65, 95% CI 0.19 to 2.22; one trial, 38 women) or delivery less than seven days after entry (RR 0.95, 95% CI 0.73 to 1.24; two trials, 51 women). Mother There were no data reported on maternal admissions to intensive care. However, there were seven cases of major maternal postpartum complications in the group allocated to planned immediate caesarean section and none in the group randomised to vaginal delivery (RR 7.21, 95% CI 1.37 to 38.08; four trials, 116 women). There were no data reported in the trials specifically relating to maternal satisfaction (postnatal). There was no significant difference between the two groups with regard to postpartum haemorrhage. A number of non-prespecified secondary outcomes were also considered in the analyses. There was a significant advantage for women in the vaginal delivery group with respect to maternal puerperal pyrexia (RR 2.98, 95% CI 1.18 to 7.53; three trials, 89 women) and other maternal infection (RR 2.63, 95% CI 1.02 to 6.78; three trials, 103 women), but no significant differences in wound infection (RR 1.16, 95% CI 0.18 to 7.70; three trials, 103 women), maternal stay more than 10 days (RR 1.27, 95% CI 0.35 to 4.65; three trials, 78 women) or the need for blood transfusion (results not estimable). There is not enough evidence to evaluate the use of a policy of planned immediate caesarean delivery for preterm babies. Further studies are needed in this area, but recruitment is proving difficult.

We included six randomised studies (involving 122 pregnant women) but only four studies (involving 116 women) contributed to the analyses. Our review found that there is not enough reliable evidence to compare planned caesarean delivery with planned vaginal delivery. Sometimes a planned caesarean cannot happen because labour progresses too quickly and sometimes, even though vaginal delivery is planned, complications arising during labour may make a caesarean section necessary. The review found that not enough women have been recruited into trials and, therefore, the decision how best to deliver a preterm baby, either cephalic or breech presentation, remains opinion and current practice within a hospital, rather than being evidence-based. All four trials were stopped early, due to difficulties with recruiting women. There were no data on serious maternal complications including admissions to intensive care unit. However, there were seven cases of major maternal postpartum complications in the group allocated to planned caesarean section (wound dehiscence, deep vein thrombosis, endotoxic shock and puerperal sepsis) and none in the group randomised to vaginal delivery. Excess blood loss from the birth canal after childbirth (postpartum haemorrhage) was not clearly different between the two groups, nor was birth asphyxia or respiratory distress syndrome or injury to the baby at birth.

10.1002/14651858.CD000078.pub3

cochrane-simplification-train-1035

cochrane-simplification-train-1035

Of the 370 records that we identified as a result of the search (excluding duplicates), we regarded six abstracts and titles as potentially relevant studies. Of these six studies, three met the inclusion criteria involving 708 participants; most trials were at moderate or high risk of bias (risk mainly due to lack of blinding and high rate of incomplete data). We did not identify any ongoing trials. Although all included studies had been published in peer-reviewed journals at the time of the search and data extraction, numerical data regarding the outcome measured in one trial involving 77 participants were insufficient for inclusion in a meta-analyses. The difference in the rates of prolonged vaginal discharge or presumed cervicitis (one study; 348 participants; risk ratio (RR), 1.29; 95% confidence interval (CI) 0.72 to 2.31; low-quality evidence) and severe vaginal bleeding (two studies; 638 participants; RR 1.21; 95% CI 0.52 to 2.82; very low-quality evidence) among the two comparison groups did not reach the level for clinically important effect. In addition, there was no difference in adverse events related to antibiotics i.e. nausea/vomiting, diarrhoea, and headache among the two comparison groups (two studies; 638 participants; RR 1.69; 95% CI 0.85 to 3.34; very low-quality evidence). There were no differences in the incidence of fever (RR, 2.23; 95% CI 0.20 to 24.36), lower abdominal pain (RR, 1.03; 95% CI 0.61 to 1.72), unscheduled medical consultation (RR 2.68, 95% CI 0.97 to 7.41), and additional self-medication (RR 1.22; 95% CI 0.56 to 2.67) between the two comparison groups (one study; 290 participants; low to very low-quality evidence). As only limited data are available from three trials with overall moderate to high risk of bias, there is insufficient evidence to support use of antibiotics to reduce infectious complications following excision of the cervical transformation zone. In addition, there were minimal data about antibiotic-related adverse events and no information on the risk of developing antibiotic resistance. Antibiotics given for infection prevention after excision of the cervical transformation zone should only be used in the context of clinical research, to avoid unnecessary prescription of antibiotics and to prevent further increases in antibiotic resistance.

We searched the literature to May 2016 and found three published randomised trials that met the review inclusion criteria. We did not identify any ongoing trials. The three included studies involved 708 participants who had undergone excisional treatment to the cervix (known as laser or large loop excision of transformation zone (LLETZ) or loop electrosurgical excision procedure (LEEP)). Two studies tested a antimicrobial vaginal pessary versus no treatment; the other tested oral antibiotics compared with placebo. We found that there was no benefit to prophylactic antibiotics after LLETZ to reduce or prevent prolonged vaginal discharge, severe vaginal bleeding, fever, lower abdominal pain, unscheduled medical consultation, and additional self-medication. There was little information on antibiotic-related adverse effects. The limited evidence available does not support routinely giving antibiotics for infection prevention after LLETZ. As there are growing concerns with antibiotic resistance, antibiotics for infection prevention after excision of the cervical transformation zones should only be used in the context of clinical trials. The quality of the evidence regarding prophylactic antibiotics for preventing severe vaginal bleeding, fever, and adverse events was very low, with evidence from other comparisons being of low quality.

10.1002/14651858.CD009957.pub2

cochrane-simplification-train-1036

cochrane-simplification-train-1036

Fourteen trials were included, but only 12 trials involving 910 women contributed data to outcome analysis. Women who exercised did not lose significantly more weight than women in the usual care group (two trials; n = 53; MD -0.10 kg; 95% confidence interval (CI) -1.90 to 1.71). Women who took part in a diet (one trial; n = 45; MD -1.70 kg; 95% CI -2.08 to -1.32), or diet plus exercise programme (seven trials; n = 573; MD -1.93 kg; 95% CI -2.96 to -0.89; random-effects, T² = 1.09, I² = 71%), lost significantly more weight than women in the usual care group. There was no difference in the magnitude of weight loss between diet alone and diet plus exercise group (one trial; n = 43; MD 0.30 kg; 95% CI -0.06 to 0.66). The interventions seemed not to affect breastfeeding performance adversely. Evidence from this review suggests that both diet and exercise together and diet alone help women to lose weight after childbirth. Nevertheless, it may be preferable to lose weight through a combination of diet and exercise as this improves maternal cardiorespiratory fitness and preserves fat-free mass, while diet alone reduces fat-free mass. This needs confirmation in large trials of high methodological quality. For women who are breastfeeding, more evidence is required to confirm whether diet or exercise, or both, is not detrimental for either mother or baby.

The review looked for randomised studies to assess the impact of dieting or exercise, or both, on women's weight loss in the months after giving birth. It paid particular attention to breastfeeding women to be sure that breastfeeding was not compromised. The review of trials found 14 studies, with 12 studies involving 910 women carrying excess weight after childbirth that contributed data for analysis. The findings suggest that diet combined with exercise or diet alone compared with usual care seemed to help with weight loss after giving birth. There is potential for these interventions to play a role in preventing future maternal obesity. There was not sufficient evidence to be sure that exercise or diet did not interfere with breastfeeding though it appeared not to in the included studies. It seems preferable to lose weight through a combination of dieting and exercise, compared to dieting alone, because exercise is thought to improve circulation and heart fitness, and to preserve lean body mass. Further research is needed.

10.1002/14651858.CD005627.pub3

cochrane-simplification-train-1037

cochrane-simplification-train-1037

We identified a total of 27 randomized controlled trials (RCTs) of migraine symptom-relieving medications, in which 9158 children and adolescents were enrolled and 7630 (range of mean age between 8.2 and 14.7 years) received medication. Twenty-four studies focused on drugs in the triptan class, including almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, sumatriptan + naproxen sodium, and zolmitriptan. Other medications studied included paracetamol (acetaminophen), ibuprofen, and dihydroergotamine (DHE). More than half of the studies evaluated sumatriptan. All but one study reported adverse event data. Most studies presented a low or unclear risk of bias, and the overall quality of evidence, according to GRADE criteria, was low to moderate, downgraded mostly due to imprecision and inconsistency. Ibuprofen was more effective than placebo for producing pain freedom at two hours in two small studies that included 162 children (RR 1.87, 95% confidence interval (CI) 1.15 to 3.04) with low quality evidence (due to imprecision). Paracetamol was not superior to placebo in one small study of 80 children. Triptans as a class of medication were superior to placebo in producing pain freedom in 3 studies involving 273 children (RR 1.67, 95% CI 1.06 to 2.62, NNTB 13) (moderate quality evidence) and 21 studies involving 7026 adolescents (RR 1.32, 95% CI 1.19 to 1.47, NNTB 6) (moderate quality evidence). There was no significant difference in the effect sizes between studies involving children versus adolescents. Triptans were associated with an increased risk of minor (non-serious) adverse events in adolescents (RD 0.13, 95% CI 0.08 to 0.18, NNTH 8), but studies did not report any serious adverse events. The risk of minor adverse events was not significant in children (RD 0.06, 95% CI − 0.04 to 0.17, NNTH 17). Sumatriptan plus naproxen sodium was superior to placebo in one study involving 490 adolescents (RR 3.25, 95% CI 1.78 to 5.94, NNTB 6) (moderate quality evidence). Oral dihydroergotamine was not superior to placebo in one small study involving 13 children. Low quality evidence from two small trials shows that ibuprofen appears to improve pain freedom for the acute treatment of children with migraine. We have only limited information on adverse events associated with ibuprofen in the trials included in this review. Triptans as a class are also effective at providing pain freedom in children and adolescents but are associated with higher rates of minor adverse events. Sumatriptan plus naproxen sodium is also effective in treating adolescents with migraine.

In our review, we looked at 27 randomized controlled trials of drugs compared to placebo to find out which treatments were effective at providing pain freedom two hours after treatment. We also wanted to know what side effects might be caused by the treatments. A total of 7630 children received medication in the studies. The evidence is current to February 2016. Each study had between 13 and 888 participants. Their average age was 12.9 years and ranged from 8.2 to 14.7 years. Nineteen of the studies were funded by the drug manufacturer. Ibuprofen appears to be effective in treating children with migraine, but the evidence is limited to only two small trials. Ibuprofen is readily available and inexpensive, making it an excellent first choice for migraine treatment. Paracetamol was not shown to be effective in providing pain freedom in children, but we only found one small study. Triptans are a type of medication designed specifically to treat migraine and are often effective at providing greater pain freedom in children and adolescents. The triptans examined in children included rizatriptan and sumatriptan, while almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan were examined in adolescents. The combination of sumatriptan plus naproxen sodium is also effective at treating adolescents with migraine. Overall, there is a risk that the triptan medications may cause minor unwanted side effects like taste disturbance, nasal symptoms, dizziness, fatigue, low energy, nausea, or vomiting. The studies did not report any serious side effects. The overall quality of the evidence provided by the review was moderate for the triptans, but low for paracetamol and ibuprofen, as we only identified a few studies. More studies need to look at the effects of each of the migraine treatments in children and adolescents separately.

10.1002/14651858.CD005220.pub2

cochrane-simplification-train-1038

cochrane-simplification-train-1038

We included 20 trials involving 2527 patients. Concealment of allocation was poorly described. Different doses (of tissue plasminogen activator, urokinase, desmoteplase or tenecteplase) were compared in 13 trials (N = 1433 patients). Different agents (tissue plasminogen activator versus urokinase, tissue-cultured urokinase versus conventional urokinase, tenecteplase versus tissue plasminogen activator) were compared in five trials (N = 875 patients). Five trials (N = 485) compared different routes of administration. As some trials compared different agents and different doses, some patients contributed to two analyses. There was an approximately three-fold increase in fatal intracranial haemorrhages in patients allocated to higher than to lower doses of the same thrombolytic drug (odds ratio (OR) 2.71, 95% confidence interval (CI) 1.22 to 6.04). There was no difference in the number of patients who were dead or dependent at the end of follow-up between those allocated higher or lower doses of thrombolytic drug (OR 0.86, 95% CI 0.62 to 1.19). Higher versus lower doses of desmoteplase were associated with more deaths at the end of follow-up (OR 3.21, 95% CI 1.23 to 8.39). There was no evidence of any benefit for intra-arterial over intravenous treatment. These limited data suggest that higher doses of thrombolytic agents may lead to higher rates of bleeding. However, the evidence is inadequate to conclude whether lower doses of thrombolytic agents are more effective than higher doses, or whether one agent is better than another, or which route of administration is the best, for acute ischaemic stroke. At present, intravenous rt-PA at 0.9mg/kg as licensed in many countries appears to represent best practice and other drugs, doses or routes of administration should only be used in randomised controlled trials.

This review aimed to find out if there were important differences between different clot-dissolving drugs. It also aimed to find out if there were differences in effect when giving the same drug in different doses or by different routes (into an artery or a vein). The review, which included 20 studies involving 2527 participants, showed that there was some evidence that lower doses of thrombolytic agents led to serious bleeding in the brain less often. However, it was not clear if the benefit from lower doses was as big as with higher doses. There was no evidence to show that one thrombolytic agent was clearly better than another, or that intra-arterial treatment was better than intravenous treatment. Therefore, more larger randomised controlled trials are required to answer questions about which drug, or dose or route of administration is best for thrombolysis. At present, rt-PA as currently licensed in many countries, should be regarded as best practice.

10.1002/14651858.CD000514.pub3

cochrane-simplification-train-1039

cochrane-simplification-train-1039

Fourteen studies including 758 participants were included in this review. The types of trauma participants had been exposed to included sexual abuse, civil violence, natural disaster, domestic violence and motor vehicle accidents. Most participants were clients of a trauma-related support service. The psychological therapies used in these studies were cognitive behavioural therapy (CBT), exposure-based, psychodynamic, narrative, supportive counselling, and eye movement desensitisation and reprocessing (EMDR). Most compared a psychological therapy to a control group. No study compared psychological therapies to pharmacological therapies alone or as an adjunct to a psychological therapy. Across all psychological therapies, improvement was significantly better (three studies, n = 80, OR 4.21, 95% CI 1.12 to 15.85) and symptoms of PTSD (seven studies, n = 271, SMD -0.90, 95% CI -1.24 to -0.42), anxiety (three studies, n = 91, SMD -0.57, 95% CI -1.00 to -0.13) and depression (five studies, n = 156, SMD -0.74, 95% CI -1.11 to -0.36) were significantly lower within a month of completing psychological therapy compared to a control group. The psychological therapy for which there was the best evidence of effectiveness was CBT. Improvement was significantly better for up to a year following treatment (up to one month: two studies, n = 49, OR 8.64, 95% CI 2.01 to 37.14; up to one year: one study, n = 25, OR 8.00, 95% CI 1.21 to 52.69). PTSD symptom scores were also significantly lower for up to one year (up to one month: three studies, n = 98, SMD -1.34, 95% CI -1.79 to -0.89; up to one year: one study, n = 36, SMD -0.73, 95% CI -1.44 to -0.01), and depression scores were lower for up to a month (three studies, n = 98, SMD -0.80, 95% CI -1.47 to -0.13) in the CBT group compared to a control. No adverse effects were identified. No study was rated as a high risk for selection or detection bias but a minority were rated as a high risk for attrition, reporting and other bias. Most included studies were rated as an unclear risk for selection, detection and attrition bias. There is evidence for the effectiveness of psychological therapies, particularly CBT, for treating PTSD in children and adolescents for up to a month following treatment. At this stage, there is no clear evidence for the effectiveness of one psychological therapy compared to others. There is also not enough evidence to conclude that children and adolescents with particular types of trauma are more or less likely to respond to psychological therapies than others. The findings of this review are limited by the potential for methodological biases, and the small number and generally small size of identified studies. In addition, there was evidence of substantial heterogeneity in some analyses which could not be explained by subgroup or sensitivity analyses. More evidence is required for the effectiveness of all psychological therapies more than one month after treatment. Much more evidence is needed to demonstrate the relative effectiveness of different psychological therapies or the effectiveness of psychological therapies compared to other treatments. More details are required in future trials in regards to the types of trauma that preceded the diagnosis of PTSD and whether the traumas are single event or ongoing. Future studies should also aim to identify the most valid and reliable measures of PTSD symptoms and ensure that all scores, total and sub-scores, are consistently reported.

We searched for all randomised controlled trials comparing psychological therapies to a control, other psychological therapies or other therapies for the treatment of PTSD in children and adolescents aged 3 to 18 years. We identified 14 studies with a total of 758 participants. The types of trauma related to the PTSD were sexual abuse, civil violence, natural disaster, domestic violence and motor vehicle accidents. Most participants were clients of a trauma-related support service. The psychological therapies used in the included studies were cognitive behavioural therapy (CBT), exposure-based, psychodynamic, narrative, supportive counselling, and eye movement desensitisation and reprocessing (EMDR). Most included studies compared a psychological therapy to a control group. No study compared psychological therapies to medications or medications in combination with a psychological therapy. There was fair evidence for the effectiveness of psychological therapies, particularly CBT, for the treatment of PTSD in children and adolescents for up to a month following treatment. More evidence is required for the effectiveness of psychological therapies in the longer term and to be able to compare the effectiveness of one psychological therapy to another. The findings of this review are limited by the potential for bias in the included studies, possible differences between studies which could not be identified, the small number of identified studies and the low number of participants in most studies.

10.1002/14651858.CD006726.pub2

cochrane-simplification-train-1040

cochrane-simplification-train-1040

We identified 10 new studies (an additional 869 participants) in the updated search. The review thus included a total of 47 studies, with 2884 children and adolescents completing treatment (mean age 12.65 years, SD 2.21 years). Twenty-three studies addressed treatments for headache (including migraine); 10 for abdominal pain; two studies treated participants with either a primary diagnosis of abdominal pain or irritable bowel syndrome, two studies treated adolescents with fibromyalgia, two studies included adolescents with temporomandibular disorders, three were for the treatment of pain associated with sickle cell disease, and two studies treated adolescents with inflammatory bowel disease. Finally, three studies included adolescents with mixed pain conditions. Overall, we judged the included studies to be at unclear or high risk of bias. Children with headache pain We found that psychological therapies reduced pain frequency post-treatment for children and adolescents with headaches (risk ratio (RR) 2.35, 95% confidence interval (CI) 1.67 to 3.30, P < 0.01, number needed to treat for an additional beneficial outcome (NNTB) = 2.86), but these effects were not maintained at follow-up. We did not find a beneficial effect of psychological therapies on reducing disability in young people post-treatment (SMD -0.26, 95% CI -0.56 to 0.03), but we did find a beneficial effect in a small number of studies at follow-up (SMD -0.34, 95% CI -0.54 to -0.15). We found no beneficial effect of psychological interventions on depression or anxiety symptoms. Children with mixed pain conditions We found that psychological therapies reduced pain intensity post-treatment for children and adolescents with mixed pain conditions (SMD -0.43, 95% CI -0.67 to -0.19, P < 0.01), but these effects were not maintained at follow-up. We did find beneficial effects of psychological therapies on reducing disability for young people with mixed pain conditions post-treatment (SMD -0.34, 95% CI -0.54 to -0.15) and at follow-up (SMD -0.27, 95% CI -0.49 to -0.06). We found no beneficial effect of psychological interventions on depression symptoms. In contrast, we found a beneficial effect on anxiety at post-treatment in children with mixed pain conditions (SMD -0.16, 95% CI -0.29 to -0.03), but this was not maintained at follow-up. Across all pain conditions, we found that adverse events were reported in seven trials, of which two studies reported adverse events that were study-related. Quality of evidence We found the quality of evidence for all outcomes to be low or very low, mostly downgraded for unexplained heterogeneity, limitations in study design, imprecise and sparse data, or suspicion of publication bias. This means our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect, or we have very little confidence in the effect estimate; or the true effect is likely to be substantially different from the estimate of effect. Psychological treatments delivered predominantly face-to-face might be effective for reducing pain outcomes for children and adolescents with headache or other chronic pain conditions post-treatment. However, there were no effects at follow-up. Psychological therapies were also beneficial for reducing disability in children with mixed chronic pain conditions at post-treatment and follow-up, and for children with headache at follow-up. We found no beneficial effect of therapies for improving depression or anxiety. The conclusions of this update replicate and add to those of a previous version of the review which found that psychological therapies were effective in reducing pain frequency/intensity for children with headache and mixed chronic pain conditions post-treatment.

This review included 47 studies with 2884 participants. The average age of the children and adolescents was 12.6 years. Most studies included young people with headache (23 studies) or stomach pain (10 studies), The remaining studies investigated children with irritable bowel syndrome, fibromyalgia, temporomandibular disorders, sickle cell disease, inflammatory bowel disease, or included samples with various chronic pain conditions. Psychological therapies reduced pain frequency immediately following treatment for children and adolescents with chronic headache, and pain intensity and anxiety for children and adolescents with other chronic pain conditions. Psychological therapies also reduced disability for children and adolescents with non-headache chronic pain conditions immediately following treatment and for children with headache and mixed chronic pain conditions up to 12 months later. We did not find any benefit of psychological treatments on reducing anxiety for children with headache or for depression in children with headache or mixed chronic pain conditions. We judged all outcomes to be low or very low-quality, meaning our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect or we have very little confidence in the effect estimate; or the true effect is likely to be substantially different from the estimate of effect.

10.1002/14651858.CD003968.pub5

cochrane-simplification-train-1041

cochrane-simplification-train-1041

We identified only one randomized controlled trial that met our inclusion criteria and no further trials were identified in subsequent updates. The included study was a trial of moderate intensity, endurance type exercise versus 'usual activities' in 25 patients with amyotrophic lateral sclerosis. The risk of bias was high and no adverse events were reported. At three months patients performing the 15 minute twice daily exercises had significantly less spasticity overall (mean reduction of -0.43, 95% confidence interval (CI) -1.03 to +0.17 in the treatment group versus an increase of +0.25, 95% CI -0.46 to +0.96 in control) but the mean change between groups was not significant (-0.68, 95% CI -1.62 to +0.26), as measured by the Ashworth scale (possible scores 0 to 5, where higher is worse). The single trial performed was too small to determine whether individualized moderate intensity endurance type exercises for the trunk and limbs are beneficial or harmful. No other medical, surgical or alternative treatment and therapy has been evaluated in a randomized fashion in this patient population. More research is needed.

This review found only one randomized trial of treatment for spasticity in motor neuron disease, which involved 25 participants, and no further trials have been found in subsequent updates. There were a number of issues with the design of the study which unfortunately reduced the certainty of the findings. At three months participants performing the 15 minute twice daily exercises had significantly less spasticity overall than control participants (mean reduction of -0.43, 95% confidence interval (CI) -1.03 to +0.17 in the treatment group versus an increase of +0.25, 95% CI -0.46 to +0.96 in control) but the mean change between groups was not significant, as measured by the Ashworth scale (a scale of spasticity, with a range of 0 to 5, where higher is worse). The trial was too small to determine whether individualized moderate intensity endurance type exercises for the trunk and limbs are beneficial or harmful. No side effects from exercise were reported. No other randomized trials of different treatments or therapies were found. Further research is needed to determine if exercise or other therapies such as anti-spasticity medication are beneficial or harmful.

10.1002/14651858.CD004156.pub4

cochrane-simplification-train-1042

cochrane-simplification-train-1042

Two studies were included involving a total of 529 people. One open quasi-randomised trial of 129 participants with traumatic hip fractures showed a reduction in PE but not mortality over a 34 day period in the filter group. The PREPIC (Prévention du Risque d'Embolie Pulmonaire par Interruption Cave) trial, was an open RCT of 400 participants with documented proximal deep vein thrombosis (DVT) or PE who received concurrent anticoagulation. Permanent VCFs prevented PE at eight years. No reduction in mortality was seen, but this reflected an older study population; the majority of deaths were due to cancer or cardiovascular causes. There was an increased incidence of (DVT) in the filter group. Adverse events were not reported. No recommendations can be drawn from the two studies. One study showed a reduction in PE rates but not mortality, but was subject to significant biases. The PREPIC study lacked statistical power to detect a reduction in PE over shorter and more clinically significant time periods. However, the trial demonstrated that permanent VCFs were associated with an increased risk of long term lower limb DVT. There is a paucity of VCFs outcome evidence when used within currently approved indications and a lack of trials on retrievable filters. Further trials are needed to assess vena caval filter safety and effectiveness.

Two trials were included in the review involving a total of 529 people. No recommendations can be made regarding filter efficacy in preventing pulmonary embolism. One trial which was conducted in 1972 showed a reduction in pulmonary embolism rates but not deaths in a group of people who suffered traumatic hip fractures and who had a filter inserted. No preventive DVT treatment was given as this was controversial at the time. Outcomes were given at 34 days.The trial participants were inadequately randomised, had a higher proportion of people who were not able to undergo surgical fixation in the control group, and outcome assessors were not blinded. In the PREPIC trial, caval filters were associated with an increased risk of blood clot formation in the legs following their insertion. This study did not demonstrate any difference in the death rates between the two groups; the participants were older (average age 73 years) with co-existing medical conditions and the majority of people died from cancer-related causes or heart problems. No details were recorded of adverse events of filters, but the numbers in this trial were not of sufficient size to detect them. There is a lack of information on the effectiveness of caval filters in other clinical scenarios, especially in the two situations where they are used most frequently and thought to be the most advantageous. These are when patients cannot be anticoagulated, or when pulmonary embolism occurs despite adequate anticoagulation. Vena caval filter use is increasing and more trials are needed to confirm their benefit and accurately assess their safety.

10.1002/14651858.CD006212.pub4

cochrane-simplification-train-1043

cochrane-simplification-train-1043

The searches identified 76 studies (302 references); 35 studies (total of 1138 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, data were not published in sufficient detail in most of these studies, so meta-analysis was limited. Few studies were considered to have a low risk of bias in any domain. It is not possible to blind participants and clinicians to physiotherapy interventions, but 11 studies did blind the outcome assessors. Forced expiratory volume in one second was the most frequently measured outcome and while many of the studies reported an improvement in those people using a vibrating device compared to before the study, there were few differences when comparing the different devices to each other or to other airway clearance techniques. One study identified an increase in frequency of exacerbations requiring antibiotics whilst using high frequency chest wall oscillation when compared to positive expiratory pressure. There were some small but significant changes in secondary outcome variables such as sputum volume or weight, but not wholly in favour of oscillating devices. Participant satisfaction was reported in 15 studies but this was not specifically in favour of an oscillating device, as some participants preferred breathing techniques or techniques used prior to the study interventions. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high level evidence. There was no clear evidence that oscillation was a more or less effective intervention overall than other forms of physiotherapy; furthermore there was no evidence that one device is superior to another. The findings from one study showing an increase in frequency of exacerbations requiring antibiotics whilst using an oscillating device compared to positive expiratory pressure may have significant resource implications. More adequately-powered long-term randomised controlled trials are necessary and outcomes measured should include frequency of exacerbations, individual preference, adherence to therapy and general satisfaction with treatment. Increased adherence to therapy may then lead to improvements in other parameters, such as exercise tolerance and respiratory function. Additional evidence is needed to evaluate whether oscillating devices combined with other forms of airway clearance is efficacious in people with cystic fibrosis.There may also be a requirement to consider the cost implication of devices over other forms of equally advantageous airway clearance techniques. Using the GRADE method to assess the quality of the evidence, we judged this to be low or very low quality, which suggests that further research is very likely to have an impact on confidence in any estimate of effect generated by future interventions.

The review included 35 studies with 1138 people with cystic fibrosis aged between 4 and 63 years of age. Studies compared different physiotherapy treatments and people were selected for one treatment or the other randomly. Not many studies looked at the same types of physiotherapy over the same period of time; studies ranged in duration from two days to 13 months. Given the differences in study design, it was difficult to combine the results from these studies in a useful way. We did not find any clear evidence that vibrating devices were better than any other form of physiotherapy which they were compared to in these studies, or that one device was better than another. One study found that people using an vibrating device needed additional antibiotics for a chest infection more often than those using positive expiratory pressure. When recommending the most suitable method of airway clearance, physiotherapists should consider the needs of the people they are treating. For the future, larger and longer trials are needed to measure the frequency of lung infections, preference, adherence to and general satisfaction with treatment, financial constraints should also be taken into consideration. We think adherence is important, because if people with cystic fibrosis are willing to stick to their physiotherapy regimen, there may be improvements in other outcomes such as exercise tolerance, respiratory function and mortality. Overall, we thought most studies had some design problems which might affect our confidence in some of the results. In about a quarter of studies there were concerns that not all the results were reported clearly and in about a third of the studies the reasons for people withdrawing from a trial were not clearly explained. In comparisons of different types of physiotherapy, a person and their physiotherapist will always know which treatment they are receiving and this might affect their answers to some questions, such as which treatment makes them feel better, but we only thought this was a problem in a few studies. We used a scoring system called GRADE to assess the quality of the evidence, we then judged it to be either low or very low quality, which suggests that further research is very likely to affect our confidence in the results in this review for of any of the interventions analysed.

10.1002/14651858.CD006842.pub4

cochrane-simplification-train-1044

cochrane-simplification-train-1044

The distribution of effects seen was generally symmetrical in the size of difference between new versus established treatments. Meta-analytic pooling indicated that, on average, new treatments were slightly more favorable both in terms of their effect on reducing the primary outcomes (hazard ratio (HR)/odds ratio (OR) 0.91, 99% confidence interval (CI) 0.88 to 0.95) and improving overall survival (HR 0.95, 99% CI 0.92 to 0.98). No heterogeneity was observed in the analysis based on primary outcomes or overall survival (I2 = 0%). Kernel density analysis was consistent with the meta-analysis, but showed a fairly symmetrical distribution of new versus established treatments indicating unpredictability in the results. This was consistent with the interpretation that new treatments are only slightly superior to established treatments when tested in RCTs. Additionally, meta-regression demonstrated that results have remained stable over time and that the success rate of new treatments has not changed over the last half century of clinical trials. The results were not significantly affected by the choice of comparator (active versus placebo/no therapy). Society can expect that slightly more than half of new experimental treatments will prove to be better than established treatments when tested in RCTs, but few will be substantially better. This is an important finding for patients (as they contemplate participation in RCTs), researchers (as they plan design of the new trials), and funders (as they assess the 'return on investment'). Although we provide the current best evidence on the question of expected 'success rate' of new versus established treatments consistent with a priori theoretical predictions reflective of 'uncertainty or equipoise hypothesis', it should be noted that our sample represents less than 1% of all available randomized trials; therefore, one should exercise the appropriate caution in interpretation of our findings. In addition, our conclusion applies to publicly funded trials only, as we did not include studies funded by commercial sponsors in our analysis.

Decisions about whether to participate in randomized trials are made more difficult because of the widespread belief that new treatments must inevitably be superior to existing (standard) treatments. Indeed, it is understandable that people hope that this will be the case. If this was actually so, however, the ethical precondition of uncertainty would often not apply. This Cochrane methodology review addresses this important question: "What is the likelihood that new treatments being compared to established treatments in randomized trials will be shown to be superior?" Four cohorts of consecutive, publicly funded, randomized trials, which altogether included 743 trials that enrolled 297,744 patients, met our inclusion criteria for this review. We found that, on average, new treatments were very slightly more likely to have favorable results than established treatments, both in terms of the primary outcomes targeted and overall survival. In other words, when new treatments are compared with established treatments in randomized trials we can expect slightly more than half will prove to be better, and slightly less than half will prove to be worse than established treatments. This conclusion applies to publicly funded trials as we did not include studies funded by commercial sponsors in our analysis.The results are consistent with the ethical preconditions for random allocation – when people are enrolled in randomized trials, the results cannot be predicted in advance as there is genuine uncertainty about which of the treatments being compared in randomized trials will prove to be superior.

10.1002/14651858.MR000024.pub3

cochrane-simplification-train-1045

cochrane-simplification-train-1045

We identified two eligible studies, both comparing nurse-led POA with POA led by non-specialist doctors, with a total of 2469 participants. One study was randomized and the other quasi-randomized. Blinding of staff and participants to allocation was not possible. In both studies, all participants were additionally assessed by a specialist doctor (anaesthetist in training), who acted as the reference standard. In neither study did participants proceed from assessment by nurse or junior doctor to surgery. Neither study reported on cancellations of surgery, gain in participant information or knowledge or perioperative complications. Reported outcomes focused on the accuracy of the assessment. One study undertook qualitative assessment of participant satisfaction with the two forms of POA in a small number of non-randomly selected participants (42 participant interviews), and both groups of participants expressed high levels of satisfaction with the care received. This study also examined economic modelling of costs of the POA as performed by the nurse and by the non-specialist doctor based on the completeness of the assessment as noted in the study and found no difference in cost. Currently, no evidence is available from RCTs to allow assessment of whether nurse-led POA leads to an increase or a decrease in cancellations or perioperative complications or in knowledge or satisfaction among surgical participants. One study, which was set in the UK, reported equivalent costs from economic models. Nurse-led POA is now widespread, and it is not clear whether future RCTs of this POA strategy are feasible. A diagnostic test accuracy review may provide useful information.

In February 2013, we searched medical databases to look for controlled trials of participants who had undergone surgery and had been randomly assigned to nurse- or doctor-led preoperative assessment (POA). We found two trials, one randomized and one quasi-randomized. Both studies were conducted in the UK and compared POA performed by the nurse with POA performed by the non-specialist doctor. One studied 1874 adult participants who were undergoing elective surgery, and the other studied 595 children who were undergoing day surgery. Neither study reported on cancellations of surgery, gain in participant information or knowledge or perioperative complications. Reported outcomes focused on the accuracy of the assessment. As there is currently no evidence from trials concerning the impact of nurse-led POA on patient outcomes, we are unable to make any recommendations for practice on the basis of this review.

10.1002/14651858.CD010160.pub2

cochrane-simplification-train-1046

cochrane-simplification-train-1046

A total of 26 trials (among which six had a cross-over design) were included. Among the 6950 randomly assigned participants, 54% (range 0 to100%) were female, mean age was 35 years (range 26 to 45.1), and the mean number of recurrences per year was 11 (range 6.3 to 17.8). Duration of treatment was two to 12 months. Risk of bias was considered high for half of the studies and unclear for the other half. A total of 14 trials compared acyclovir versus placebo, four trials compared valacyclovir versus placebo and 2 trials compared valacyclovir versus no treatment. Three trials compared famciclovir versus placebo. Two trials compared valacyclovir versus famciclovir and one trial compared acyclovir versus valacyclovir versus placebo. We analyzed data from 22 trials for the outcome: risk of having at least one clinical recurrence. We could not obtain the outcome data for four trials. In placebo-controlled trials, there was a low quality evidence that the risk of having at least one clinical recurrence was reduced with acyclovir (nine parallel-group trials, n = 2049; pooled RR 0.48, 95% confidence interval (CI) 0.39 to 0.58), valacyclovir (four trials, n = 1788; pooled RR 0.41, 95% CI 0.24 to 0.69), or famciclovir (two trials, n = 732; pooled RR 0.57, 95% CI 0.50 to 0.64). The six cross-over trials showed larger treatment effects on average than the parallel-group trials. We found evidence of a small-study effect for acyclovir placebo-controlled trials (adjusted pooled RR 0.61, 95% CI 0.49 to 0.75). In analyzing parallel-group trials by daily dose, no clear evidence was found of a dose-response relationship for any drug. In head-to-head trials, the risk of having at least one recurrence was increased with valacyclovir rather than acyclovir (one trial, n = 1345; RR 1.16, 95% CI 1.01 to 1.34) and was not significantly different from that seen with famciclovir as compared with valacyclovir (one trial, n = 320; RR 1.18, 95% CI 0.86 to 1.63). We included 16 parallel-arm trials in a network meta-analysis and we were unable to determine which of the drugs was most effective in reducing the risk of at least one clinical recurrence (after adjustment for small-study effects, pooled RR 0.83, 95% CI 0.61 to 1.11 for valacyclovir vs acyclovir; pooled RR 1.04, 95% CI, 0.71 to 1.49 for famciclovir vs acyclovir; and pooled RR 1.26, 95% CI 0.89 to 1.75 for famciclovir vs valacyclovir). Safety data were sought but were reported as total numbers of adverse events. Owing to risk of bias and inconsistency, there is low quality evidence that suppressive antiviral therapy with acyclovir, valacyclovir or famciclovir in pacients experiencing at least four recurrences of genital herpes per year decreases the number of pacients with at least one recurrence as compared with placebo. Network meta-analysis of the few direct comparisons and the indirect comparisons did not show superiority of one drug over another.

A total of 26 trials including 6950 patients were included in this review. Fifty-four percent of these patients were female, mean age was 35 years, and mean number of recurrences per year before entry into the trials was 11. Duration of treatment in trials ranged from two to 12 months. A total of 14 trials compared acyclovir versus placebo. Four trials compared valacyclovir versus placebo and two trials compared valacyclovir versus no treatment. Three trials compared famciclovir versus placebo. Two trials compared valacyclovir versus famciclovir, and one trial compared acyclovir versus valacyclovir versus placebo. Among the 26 included trials, 22 declared pharmaceutical company funding. The last search for studies was carried out in February 2014. Suppressive antiviral therapy with acyclovir, valacyclovir, or famciclovir in patients experiencing at least four recurrences per year decreases the number of patients having at least one recurrence compared with placebo. There is no evidence that suggests that any of these drugs is superior to the others. Althought the three antiviral drugs showed better results compared with placebo, we are uncertain as to how much a difference there are likely to make, because of issues with the conduct and reporting of studies, and inconsistency of their results. The quality of the evidence is low and we think that the size of the effects is likely to change with more research. Because few studies compared the three drugs against one other, we are moderately confident in the fact that there is no difference between the three drugs in terms of effectiveness.

10.1002/14651858.CD009036.pub2

cochrane-simplification-train-1047

cochrane-simplification-train-1047

Twenty six trials involving a total of 2933 participants were included in the review. One trial included three treatment groups. In 11 RCTs amongst 1389 people, there was no significant difference in need for recatheterisation, although recatheterisation after removal at night was more likely to be during working hours. Pooled results demonstrated that, following urological surgery and procedures, patients whose indwelling urethral catheters were removed at midnight passed significantly larger volumes at their first void (Difference (fixed) 96 ml; 95% CI 62 to 130). Similar findings were reported for patients following TURP (Difference (fixed) 27; 95% CI 23 to 31). Removal at midnight was also associated with longer time to first void, and shorter lengths of hospitalisation (relative risk of not going home on day of removal = 0.71, 95% CI 0.64 to 0.79). Results in 13 trials amongst 1422 participants having early rather than delayed catheter removal were consistent with a higher risk of voiding problems and a lower risk of infection, with shorter hospitalisation. In three trials involving 234 participants the data were too few to assess differential effects of catheter clamping compared with free drainage prior to withdrawal. No eligible trials compared flexible with fixed duration of catheterisation, or assessed prophylactic alpha sympathetic blocker drugs prior to catheter removal. There is suggestive but inconclusive evidence of a benefit from midnight removal of the indwelling urethral catheter. There are resource implications but the magnitude of these is not clear from the trials. The evidence also suggests shorter hospital stay after early rather than delayed catheter removal but the effects on other outcomes are unclear. There is little evidence on which to judge other aspects of management, such as catheter clamping.

This review identified 26 controlled trials looking at the best strategies for removal of catheters. In 11 studies comparing late night versus early morning removal, removal at midnight resulted in a longer time to first void and patients passing significantly larger volumes, although these findings varied widely. There was no apparent effect on the number of patients who required recatheterisation because of subsequent urinary retention, but patients with catheters removed at midnight were discharged from hospital significantly earlier than those with morning removal. Based on findings from 13 trials, limiting how long a catheter was left in place was linked to a shorter stay in hospital and less risk of infection. The information available from three trials was too limited to assess whether clamping prior to removal, to simulate normal filling of the bladder, improved outcomes.

10.1002/14651858.CD004011.pub3

cochrane-simplification-train-1048

cochrane-simplification-train-1048

Twenty-three trials involving 2861 older and mainly female patients with proximal femoral fractures are included. Cemented prostheses, when compared with uncemented prostheses (6 trials, 899 participants) were associated with a less pain at a year or later and improved mobility. No significant difference in surgical complications was found. One trial of 220 participants compared a hydroxyapatite coated hemiarthroplasty with a cemented prosthesis and reported no notable differences between the two prosthesis. Comparison of unipolar hemiarthroplasty with bipolar hemiarthroplasty (7 trials, 857 participants, 863 fractures) showed no significant differences between the two types of implant. Seven trials involving 734 participants compared hemiarthroplasty with a total hip replacement (THR). Most studies involved cemented implants. Dislocation of the prosthesis was more common with the THR but there was a general trend within these studies to better functional outcome scores for those treated with the THR. There is good evidence that cementing the prostheses in place will reduce post-operative pain and lead to better mobility. From the trials to date there is no evidence of any difference in outcome between bipolar and unipolar prosthesis. There is some evidence that a total hip replacement leads to better functional outcome than a hemiarthroplasty. Further well-conducted randomised trials are required.

Twenty-three trials involving 2861 older and mainly female patients with hip fractures are included in this review. The findings from the three main comparisons are summarised here. Six studies involving 899 participants compared a press fit arthroplasty with one that was secured in place with bone cement. Those joints that were cemented in place resulted in less pain and better mobility than those that were of the press fit type. Seven trials involving 857 participants compared those implants which have a second joint built into them (bipolar hemiarthroplasties) with those without this additional joint (unipolar hemiarthroplasties). No notable differences between these two types of implant were demonstrated. Seven studies of 734 participants compared different types of hemiarthroplasty with a total hip replacement. Most implants had been cemented in place. There was a trend to better functional outcomes after total hip replacement, but firm conclusions could not be made because of the lack of patient numbers. There is good evidence that people with arthroplasties that are cemented in place have less pain and better mobility after the operation than those, which are inserted as a press fit. There is limited evidence that a total hip replacement leads to better functional outcome than a hemiarthroplasty.

10.1002/14651858.CD001706.pub4

cochrane-simplification-train-1049

cochrane-simplification-train-1049

Forty-six comparisons (from 42 trials) were included (as compared with 26 comparisons in the last update) including a wide range of drugs in inpatient and outpatient settings. All were randomized controlled trials except two studies. Interventions usually targeted doctors, although some studies attempted to influence prescriptions by pharmacists and nurses. Drugs evaluated were anticoagulants, insulin, aminoglycoside antibiotics, theophylline, anti-rejection drugs, anaesthetic agents, antidepressants and gonadotropins. Although all studies used reliable outcome measures, their quality was generally low. This update found similar results to the previous update and managed to identify specific therapeutic areas where the computerized advice on drug dosage was beneficial compared with routine care: 1. it increased target peak serum concentrations (standardized mean difference (SMD) 0.79, 95% CI 0.46 to 1.13) and the proportion of people with plasma drug concentrations within the therapeutic range after two days (pooled risk ratio (RR) 4.44, 95% CI 1.94 to 10.13) for aminoglycoside antibiotics; 2. it led to a physiological parameter more often within the desired range for oral anticoagulants (SMD for percentage of time spent in target international normalized ratio +0.19, 95% CI 0.06 to 0.33) and insulin (SMD for percentage of time in target glucose range: +1.27, 95% CI 0.56 to 1.98); 3. it decreased the time to achieve stabilization for oral anticoagulants (SMD -0.56, 95% CI -1.07 to -0.04); 4. it decreased the thromboembolism events (rate ratio 0.68, 95% CI 0.49 to 0.94) and tended to decrease bleeding events for anticoagulants although the difference was not significant (rate ratio 0.81, 95% CI 0.60 to 1.08). It tended to decrease unwanted effects for aminoglycoside antibiotics (nephrotoxicity: RR 0.67, 95% CI 0.42 to 1.06) and anti-rejection drugs (cytomegalovirus infections: RR 0.90, 95% CI 0.58 to 1.40); 5. it tended to reduce the length of time spent in the hospital although the difference was not significant (SMD -0.15, 95% CI -0.33 to 0.02) and to achieve comparable or better cost-effectiveness ratios than usual care; 6. there was no evidence of differences in mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, anti-rejection drugs and antidepressants. For all outcomes, statistical heterogeneity quantified by I2 statistics was moderate to high. This review update suggests that computerized advice for drug dosage has some benefits: it increases the serum concentrations for aminoglycoside antibiotics and improves the proportion of people for which the plasma drug is within the therapeutic range for aminoglycoside antibiotics. It leads to a physiological parameter more often within the desired range for oral anticoagulants and insulin. It decreases the time to achieve stabilization for oral anticoagulants. It tends to decrease unwanted effects for aminoglycoside antibiotics and anti-rejection drugs, and it significantly decreases thromboembolism events for anticoagulants. It tends to reduce the length of hospital stay compared with routine care while comparable or better cost-effectiveness ratios were achieved. However, there was no evidence that decision support had an effect on mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, anti-rejection drugs and antidepressants. In addition, there was no evidence to suggest that some decision support technical features (such as its integration into a computer physician order entry system) or aspects of organization of care (such as the setting) could optimize the effect of computerized advice. Taking into account the high risk of bias of, and high heterogeneity between, studies, these results must be interpreted with caution.

We sought clinical trial evidence from scientific databases to evaluate the effectiveness of these computer systems. The evidence is current to January 2012. We found data from 42 trials (40 randomized controlled trials (trials that allocate people at random to receive one of a number of drugs or procedures) and two non-randomized controlled trials). Computerized advice for drug dosage can benefit people taking certain drugs compared with empiric dosing (where a dose is chosen based on a doctor's observations and experience) without computer assistance. When using the computer system, healthcare professionals prescribed appropriately higher doses of the drugs initially for aminoglycoside antibiotics and the correct drug dose was reached more quickly for oral anticoagulants. It significantly decreased thromboembolism (blood clotting) events for anticoagulants and tended to reduce unwanted effects for aminoglycoside antibiotics and anti-rejection drugs (although not an important difference). It tended to reduce the length of hospital stay compared with routine care with comparable or better cost-effectiveness. There was no evidence of effects on death or clinical side events for insulin (low blood sugar (hypoglycaemia)), anaesthetic agents, anti-rejection drugs (drugs taken to prevent rejection of a transplanted organ) and antidepressants. The quality of the studies was low so these results must be interpreted with caution.

10.1002/14651858.CD002894.pub3

cochrane-simplification-train-1050

cochrane-simplification-train-1050

We identified five RCTs including 663 patients with one to four brain metastases. The risk of bias associated with lack of blinding was high and impacted to a greater or lesser extent on the quality of evidence for all of the outcomes. Adding upfront WBRT decreased the relative risk of any intracranial disease progression at one year by 53% (RR 0.47, 95% CI 0.34 to 0.66, P value < 0.0001, I2 =34%, Chi2 P value = 0.21, low quality evidence) but there was no clear evidence of a difference in  OS (HR 1.11, 95% CI 0.83 to 1.48, P value = 0.47, I2 = 52%, Chi2 P value = 0.08, low quality evidence) and PFS (HR 0.76, 95% CI 0.53 to 1.10, P value = 0.14, I2 = 16%, Chi2 P value = 0.28, low quality evidence). Subgroup analyses showed that the effects on overall survival were similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The evaluation of the impact of upfront WBRT on NF, HRQL and neurological adverse events was limited by the unclear and high risk of reporting, performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies. There is low quality evidence that adding upfront WBRT to surgery or SRS decreases any intracranial disease progression at one year. There was no clear evidence of an effect on overall and progression free survival. The impact of upfront WBRT on neurocognitive function, health related quality of life and neurological adverse events was undetermined due to the high risk of performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies

We included five studies. These studies reported the effect of adding whole brain radiation to surgery or radiosurgery in terms of survival, brain disease progression, quality of life and treatment side effects. The sample size of these studies ranged from 19 to 359 patients. Adding whole brain radiotherapy to surgery or radiosurgery reduces brain metastases progression rates substantially but there was no clear evidence of an effect on survival and it is unclear whether it may cause side effects such as memory loss. We considered the evidence on survival, intracranial disease progression, neurocognitive function, quality of life and treatment side effects to be of low quality.

10.1002/14651858.CD009454.pub2

cochrane-simplification-train-1051

cochrane-simplification-train-1051

Four studies (108 participants) were included. Three studies investigated cyclosporin A (CSA) with or without prednisone versus prednisone or no treatment and one compared chlorambucil plus prednisone versus no treatment. Outcome data was only available for complete or partial remission and doubling of serum creatinine. There was a significant increase in the number of participants who obtained complete or partial remission with CSA plus low dose prednisone versus prednisone alone (one study, 49 participants: RR 8.85, 95% CI 1.22 to 63.92). Pooled analyses were not performed due to the heterogeneity of the data. Adult patients treated with CSA at an initial dose of 3.5-5 mg/kg/d in two divided doses perhaps in combination with oral prednisolone 0.15 mg/kg/d are more likely to achieve a partial remission of the nephrotic syndrome compared with symptomatic treatment or prednisolone alone. However, there is a probability of deterioration of kidney function due to the nephrotoxic effect of CSA in the long term. For CSA, a larger controlled trial with longer follow-up should be performed to prove the benefit of this regimen not only on proteinuria but also on the preservation of kidney function. Present available data do not support the general use of alkylating substances for the treatment of FSGS in adults.

This systematic review identified four studies (108 participants) investigating immunosuppressive treatments for adults with biopsy-proven FSGS. Adult patients treated with cyclosporin A in combination with prednisone were more likely to achieve partial remission of nephrotic syndrome compared with prednisone alone, however this result is based on only one small study. No data was available on the progression to kidney failure or death.

10.1002/14651858.CD003233.pub2

cochrane-simplification-train-1052

cochrane-simplification-train-1052

Two studies were included that enrolled people with CNV located at 100 microns or more from the foveal centre. One study compared photocoagulation with observation. At the final examination, 16/35 participants randomised to photocoagulation versus 31/35 randomised to observation had visual acuity of 20/100 or worse after six to 48 months. The second study randomised 27 eyes (26 participants) to photocoagulation with three laser wavelengths (nine eyes per group). The number of eyes losing two or more lines was two (577 nm), three (590 nm) and three (620 nm) after three to 17 months. In both studies comparisons were made using outcomes assessed at the final examination. As the final examination took place at different follow-up times it was difficult to interpret the findings and it was impossible to extract data for further analyses. Despite its use over several years the effectiveness of laser photocoagulation for myopic CNV has not been established. Although there was a suggestion of short-term effectiveness in one small study on non-subfoveal CNV the results were potentially biased. Observational studies suggest that the enlargement of the atrophic laser scar after laser treatment of non-subfoveal CNV could be a potentially vision-threatening long-term complication, even in eyes free of CNV recurrence.

This review found one small study, including 70 participants, which compared laser photocoagulation with no treatment for people with this disease. This study was inadequately reported and analysed, although it suggested a benefit with photocoagulation during the first two years of follow up. Another small study compared three laser wavelengths to achieve photocoagulation of the lesion, but actually had very little power to demonstrate a difference between them as only 27 participants were included. Therefore, despite its widespread use for many years, the amount of benefit achieved with photocoagulation and the possibility that it is maintained over the years remains unknown. Furthermore, these and other studies suggest that the enlargement of the laser scar could be a potentially vision-threatening long-term complication after two years, since it may cause the gradual occurrence of a blind spot in the centre of the visual field due to progressive atrophy of the retina.

10.1002/14651858.CD004765.pub2

cochrane-simplification-train-1053

cochrane-simplification-train-1053

We identified 13 studies (917 participants). The evaluated treatment modalities consisted of a topical treatment (11 studies), an oral treatment (2 studies) and a parenteral treatment (2 studies). Seven studies used a placebo or no intervention control group, whereas all others also or solely compared active treatment groups. No study evaluated the effects of ice or the application of cold or hot bandages. Overall, the risk of bias in individual trials was moderate to high, although poor reporting hampered a full appreciation of the risk in most studies. The overall quality of the evidence for each of the outcomes varied from low to moderate mainly due to risk of bias and imprecision, with only single trials contributing to most comparisons. Data on primary outcomes improvement of signs and symptoms and side effects attributed to the study treatment could not be statistically pooled because of the between-study differences in comparisons, outcomes and type of instruments to measure outcomes. An array of topical treatments, such as heparinoid or diclofenac gels, improved pain compared to placebo or no intervention. Compared to placebo, oral non-steroidal anti-inflammatory drugs reduced signs and symptoms intensity. Safety issues were reported sparsely and were not available for some interventions, such as notoginseny creams, parenteral low-molecular-weight heparin or defibrotide. Although several trials reported on adverse events with topical heparinoid creams, Essaven gel or phlebolan versus control, the trials were underpowered to adequately measure any differences between treatment modalities. Where reported, adverse events with topical treatments consisted mainly of local allergic reactions. Only one study of 15 participants assessed thrombus extension and symptomatic venous thromboembolism with either oral non-steroidal anti-inflammatory drugs or low-molecular-weight heparin, and it reported no cases of either. No study reported on the development of suppurative phlebitis, catheter-related bloodstream infections or quality of life. The evidence about the treatment of acute infusion superficial thrombophlebitis is limited and of low quality. Data appear too preliminary to assess the effectiveness and safety of topical treatments, systemic anticoagulation or oral non-steroidal anti-inflammatory drugs.

In the current review, which looked for studies up to April 2015, we identified 13 studies involving 917 participants. Eleven studies evaluated topical treatments (medication applied to the skin), two trials studied an oral treatment, and two studies assessed a parenteral treatment (via injection or infusion). Seven studies used a control group that received no treatment or a placebo, whereas all others also or solely compared two active treatment groups. No study evaluated the effects of ice or the application of cold or hot bandages. Overall, topical treatments resulted in a higher and faster improvement of the clinical signs and symptoms compared to placebo or no intervention. Reporting on safety data was limited, with no available information on some treatments (notoginseny creams, parenteral low-molecular-weight heparin or defibrotide). Although some studies reported on harmful side effects with topical heparinoid creams, Essaven gel or phlebolan, the trials were too small in size to adequately measure any differences between treatments. Reported side effects of topical treatments consisted mainly of local allergic reactions. Only one study with 15 participants assessed anything other than localised control of the condition. That study reported on extension of the clot or symptomatic venous thromboembolism (when the blood clot breaks loose and travels in the blood stream), observing no cases when treated orally with non-steroidal anti-inflammatory drugs or with low-molecular-weight heparin. None of the studies reported on the development of suppurative or septic phlebitis (when pus is formed inside the vein or around the vein wall or both), catheter-related bloodstream infections or quality of life. Some of the included studies may have been biased due to design limitations, but we could not always assess this risk because the original researchers did not always provide enough information to judge. The overall quality of the evidence for each of the outcomes varied from low to moderate, mainly because the studies had design flaws or were very small. We could not analyse data on primary outcomes together because the trials examined different treatments, in different ways, looking at different outcomes. In short, the evidence about the treatment of acute infusion superficial thrombophlebitis is limited and of low quality, and we do not have enough information to recommend the use of any of the treatments studied.

10.1002/14651858.CD011015.pub2

cochrane-simplification-train-1054

cochrane-simplification-train-1054

The screening process identified 61 included studies which encompass 58 induction phases (5111 patients randomised to placebo) and 12 maintenance phases (1579 patients randomised to placebo). For induction trials, the pooled estimate of placebo response was 33% (95% CI 30% to 36%) while the pooled estimate of placebo remission was 12% (95% CI 9% to 15%). For maintenance trials, the pooled estimate of placebo response was 23% (95% CI 19% to 28%) while the pooled estimate of placebo remission was 17% (95% CI 10% to 27%). Studies enrolling patients with more active disease confirmed objectively by endoscopy were associated with significantly lower placebo remission and response rates than trials enrolling patients with less active disease (27% versus 4%, OR 2.60, 95% CI 1.25 to 5.42, P = 0.01 for UCDAI endoscopy sub score ≥1 versus ≥ 2 for remission; and 27% versus 4%, OR 1.70, 95% CI 1.02 to 2.82, P = 0.02 for UCDAI endoscopy sub score greater than or equal to one versus greater than or equal to two for response). With respect to drug class, the lowest placebo response and remission rates were observed in trials evaluating corticosteroids (23%; 95% CI 19 to 29%, and 5%; 95% CI 2 to 11%, respectively). Trials of biologics had the highest placebo response rate (35%; 95% CI 30 to 41%), while trials evaluating aminosalicylates had the highest placebo remission rate (18%; 95% CI 12 to 24%). Disease duration of greater than five years prior to enrolment was associated with a significantly lower placebo response rate compared to disease duration of less than or equal to five years (29% versus 47%, respectively; OR 0.54, 95% CI 0.32 to 0.92, P = 0.02). The requirement of a minimum rectal bleeding score for study eligibility was associated with an increased placebo response rate compared to studies that did not use rectal bleeding for trial eligibility (37% versus 32%, respectively; OR 1.70, 95% CI 1.02 to 2.82, P = 0.02). Finally, the time point of primary outcome assessment was found to be significantly associated with placebo remission rates such that every one week increment in endpoint assessment was associated with a 6% increase in the placebo remission rate (OR 1.06, 95% CI 1.02 to 1.10, P = 0.01). Cumulative meta-analysis indicated a consistent increase in the placebo response rate from 1987 to 2007 (from 13% to 33%), although rates have remained constant from 2008 to 2015 (32% to 34%). Similarly, placebo remission rates increased from 1987 to 2007 (5% to 14%) but have remained constant from 2008 to 2015 (12 to 14%). On meta-regression, there were no statistically significant differences between the 1987-2007 and 2008-2015 point estimates for both response (P = 0.81) and remission (P = 0.32). Placebo response and remission rates vary according to endoscopic disease severity and rectal bleeding score at trial entry, class of agent, disease duration, and the time point at which the primary outcome was measured. These observations have important implications for the design and conduct of future clinical trials in UC and will help researchers design trials, determine required sample sizes and also provide useful information about trial design features which should be considered when planning new trials.

Sixty-one trials were included which evaluated 58 induction phases (5111 patients randomised to placebo) and 12 maintenance phases (1579 patients randomised to placebo). The researchers found that placebo response and remission rates varied according to which class of drug was being tested with the highest placebo response rates observed for biological drugs (genetically engineered medications made from living organisms). The highest placebo remission rates were observed for trials evaluating aminosalicylates (a type of anti-inflammatory drug). The lowest placebo response and remission rates were in trials that assessed corticosteroids (drugs that suppress inflammation and immunity). The requirement of a minimum rectal bleeding score for study eligibility was associated with an increased placebo response rate compared to studies that did not use rectal bleeding for trial eligibility. The time point of primary outcome assessment was found to be significantly associated with placebo remission rates such that every one week increment in endpoint assessment was associated with an increase in the placebo remission rate. There were several trial design features that were associated with lower placebo response and remission rates. A key finding was that trials enrolling patients with more severe endoscopic disease (i.e. inflammation of the colon as confirmed by a colonoscopy) at trial entry were associated with lower placebo response and remission rates, which underpins the importance of objectively ensuring that patients enrolled into UC trials have sufficient disease severity. Disease duration of greater than five years prior to trial enrolment was associated with a significantly lower placebo response rate compared to disease duration of less than or equal to five years. The researchers also found that placebo rates have remained stable from 2008 to 2015. In conclusion, placebo response and remission rates vary according to endoscopic disease severity and rectal bleeding score at trial entry, drug class, disease duration, and the time point at which the primary outcome was measured. The overall findings will help researchers conducting trials to design their studies, determine the number of patients required for their planned trials and also provide useful information about trial design features which should be considered when planning new trials.

10.1002/14651858.CD011572.pub2

cochrane-simplification-train-1055

cochrane-simplification-train-1055

Twenty-nine eligible trials, involving 5247 participants, were identified. Participants randomised to a dopamine agonist were less likely to develop dyskinesia (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.43 to 0.59; P < 0.00001), dystonia (OR 0.64, 95% CI 0.51 to 0.81; P = 0.0002) and motor fluctuations (OR 0.75, 95% CI 0.63 to 0.90; P = 0.002) than levodopa-treated participants. However, various 'non-motor' side-effects, including oedema (OR 3.68, 95% CI 2.62 to 5.18; P < 0.00001), somnolence (OR 1.49, 95% CI 1.12 to 2.00; P = 0.007), constipation (OR 1.59, 95% CI 1.11 to 2.28; P = 0.01), dizziness (OR 1.45, 95% CI 1.09 to 1.92; P = 0.01), hallucinations (OR 1.69, 95% CI 1.13 to 2.52; P = 0.01) and nausea (OR 1.32, 95% CI 1.05 to 1.66; P = 0.02) were all increased in agonist-treated participants (compared with levodopa-treated participants). Agonist-treated participants were also significantly more likely to discontinue treatment due to adverse events (OR 2.49, 95% CI 2.08 to 2.98; P < 0.00001). Finally symptomatic control of Parkinson's disease was better with levodopa than with agonists, but data were reported too inconsistently and incompletely to meta-analyse. This meta-analysis confirms that motor complications are reduced with dopamine agonists compared to levodopa, but also establishes that other important side-effects are increased and symptom control is poorer with agonists. Larger, long-term comparative trials assessing patient-rated quality of life are needed to assess more reliably the balance of benefits and risks of dopamine agonists compared to levodopa.

Twenty-nine eligible trials, involving 5247 participants, were identified. It confirms reports from individual trials that motor complications are reduced with dopamine agonists compared to levodopa, but also demonstrates that other important side-effects are increased and symptom control is poorer with agonists. Unfortunately, the balance of risks and benefits remains unclear highlighting the need for further studies assessing patient-rated overall quality of life and economic measures as their primary outcomes.

10.1002/14651858.CD006564.pub2

cochrane-simplification-train-1056

cochrane-simplification-train-1056

One study reporting on 154 neonates was found eligible. No significant difference between surgical closure and indomethacin treatment was found for in-hospital mortality, chronic lung disease, necrotising enterocolitis, sepsis, creatinine level or intraventricular haemorrhage. There was a significant increase in the surgical group in the incidence of pneumothorax (risk ratio (RR) 2.68; 95% confidence interval (CI) 1.45 to 4.93; risk difference (RD) 0.25; 95% CI 0.11 to 0.38; number needed to treat to harm (NNTH) 4 (95% CI 3 to 9)) and retinopathy of prematurity stage III and IV (RR 3.80; 95% CI 1.12 to 12.93; RD 0.11; 95% CI 0.02 to 0.20; NNTH 9 (95% CI 5 to 50)) compared to the indomethacin group. There was a statistically significant decrease in failure of ductal closure rate in the surgical group as compared to the indomethacin group (RR 0.04; 95% CI 0.01 to 0.27; RD -0.32; 95% CI -0.43 to -0.21, number needed to treat to benefit (NNTB) 3 (95% CI 2 to 4)). No new trials were identified for inclusion in the 2012 update. There are insufficient data to conclude whether surgical ligation or medical treatment with indomethacin is preferred as the initial treatment for symptomatic PDA in preterm infants.

Only one randomised controlled study could be included in this review (including 154 preterm infants that needed breathing support). Indomethacin and surgery gave similar benefits. There were no differences in deaths during the hospital stay, chronic lung disease, necrotising enterocolitis, cerebral or other bleeding. Surgery was more effective in closing the PDA (three needed to treat for one to benefit) but it was associated with complications (pneumothorax and retinopathy of prematurity). The one study found was carried out over 30 years ago. Clinical practice has changed a great deal and surgical closure of a PDA is safer. Therefore, whether the results of the study are applicable today is debatable. Updates of this review in July 2007 and February 2012 did not identify any additional randomised controlled studies for inclusion, but three observational studies indicated an increased risk for one or more of the following outcomes associated with PDA ligation: chronic lung disease, retinopathy of prematurity and neurosensory impairment.

10.1002/14651858.CD003951.pub3

cochrane-simplification-train-1057

cochrane-simplification-train-1057

Three trials involving 106 infants were included in this review. In one trial (n = 20) CPT was no better than standard care in clearing secretions. No increase in the risk of intraventricular haemorrhage was noted. Two trials compared different types of active CPT. One trial (n = 56) showed that non-resolved atelectasis was reduced in more neonates receiving the lung squeezing technique (LST) when compared to postural drainage, percussion and vibration (PDPV) (RR 0.25; 95% CI 0.11 to 0.57). No difference in secretion clearance or in the rate of intraventricular haemorrhage or periventricular leucomalacia was demonstrated. The other trial (n = 30) showed that the use of percussion or 'cupping' resulted in an increased incidence of hypoxaemia (RR 0.53; 95% CI 0.28 to 0.99) and increased oxygen requirements (MD -9.68; 95% CI -14.16 to -5.20) when compared with contact heel percussion. There was insufficient information to adequately assess important short and longer-term outcomes, including adverse effects. The results of this review do not provide sufficient evidence on which to base clinical practice. There is a need for larger randomised controlled trials to address these issues.

This review found no clear overall benefit or harm from chest physiotherapy. Some individual chest physiotherapy techniques were more beneficial than others in resolving atelectasis and maintaining oxygenation. These results do not support one technique over another. Due to the limited number, poor quality and age of trials in this review, there is not enough evidence to determine whether or not chest physiotherapy is beneficial or harmful in the treatment of infants being ventilated in today's intensive care units. Further good quality trials are needed to address this issue.

10.1002/14651858.CD006445.pub2

cochrane-simplification-train-1058

cochrane-simplification-train-1058

We included 91 studies that evaluated seven tests — blood tests for human placental lactogen (hPL), oestriol, placental growth factor (PlGF) and uric acid, ultrasound EFW and placental grading and urinary oestriol — in a total of 175,426 pregnant women, in which 15,471 pregnancies ended in the birth of a small baby and 740 pregnancies which ended in stillbirth. The quality of included studies was variable with most domains at low risk of bias although 59% of studies were deemed to be of unclear risk of bias for the reference standard domain. Fifty-three per cent of studies were of high concern for applicability due to inclusion of only high- or low-risk women. Using all available data for SGA (86 studies; 159,490 pregnancies involving 15,471 SGA infants), there was evidence of a difference in accuracy (P < 0.0001) between the seven tests for detecting pregnancies that are SGA at birth. Ultrasound EFW was the most accurate test for detecting SGA at birth with a diagnostic odds ratio (DOR) of 21.3 (95% CI 13.1 to 34.6); hPL was the most accurate biochemical test with a DOR of 4.78 (95% CI 3.21 to 7.13). In a hypothetical cohort of 1000 pregnant women, at the median specificity of 0.88 and median prevalence of 19%, EFW, hPL, oestriol, urinary oestriol, uric acid, PlGF and placental grading will miss 50 (95% CI 32 to 68), 116 (97 to 133), 124 (108 to 137), 127 (95 to 152), 139 (118 to 154), 144 (118 to 161), and 144 (122 to 161) SGA infants, respectively. For the detection of pregnancies ending in stillbirth (21 studies; 100,687 pregnancies involving 740 stillbirths), in an indirect comparison of the four biochemical tests, PlGF was the most accurate test with a DOR of 49.2 (95% CI 12.7 to 191). In a hypothetical cohort of 1000 pregnant women, at the median specificity of 0.78 and median prevalence of 1.7%, PlGF, hPL, urinary oestriol and uric acid will miss 2 (95% CI 0 to 4), 4 (2 to 8), 6 (6 to 7) and 8 (3 to 13) stillbirths, respectively. No studies assessed the accuracy of ultrasound EFW for detection of pregnancy ending in stillbirth. Biochemical markers of placental dysfunction used alone have insufficient accuracy to identify pregnancies ending in SGA or stillbirth. Studies combining U and placental biomarkers are needed to determine whether this approach improves diagnostic accuracy over the use of ultrasound estimation of fetal size or biochemical markers of placental dysfunction used alone. Many of the studies included in this review were carried out between 1974 and 2016. Studies of placental substances were mostly carried out before 1991 and after 2013; earlier studies may not reflect developments in test technology.

Of the 91 included studies, 86 had information on small babies, of which 18 also looked at stillbirth; another five studies only looked at stillbirth. The most accurate test for detecting a small baby was ultrasound scan to estimate a baby’s weight. Of the substances measured in mother’s blood, human placental lactogen (hPL), a hormone produced by the placenta during pregnancy, was the most accurate. There was only one study which looked at both ultrasound scanning and measurement of a placental substance. Placental growth factor (PlGF) was the most accurate test of a placental substance to identify a baby that would be stillborn; there were no studies of ultrasound scanning to detect a baby that would be stillborn. Tests of placental substances were better at identifying a baby at risk of stillbirth than detecting a small baby. Many of the studies included in this review were carried out between 1974 and 2016. Studies of placental substances were mostly carried out before 1991 and after 2013; earlier studies may not reflect developments in test technology. More studies are needed to find out whether a combination of ultrasound scans and mother’s blood tests could improve identification of pregnancies which end in the birth of a small baby or in a stillborn baby. No studies were identified for this review that looked at the accuracy of ultrasound and blood tests used together.

10.1002/14651858.CD012245.pub2

cochrane-simplification-train-1059

cochrane-simplification-train-1059

We included 15 RCTs that compared eight different interventions versus no treatment for 1992 women in five countries. Most interventions were assessed by only one RCT with evidence quality ranging from very low to moderate. The main limitation was imprecision, associated with small sample sizes and low event rates. Pelvic floor muscle training (PFMT) compared with no treatment (three RCTs) - peri-operative intervention The simplest of the PFMT programmes required women to attend six perioperative consultations in the three months surrounding prolapse surgery. Trial results provided no clear evidence of a difference between groups in objective failure at any site at 12 to 24 months (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.56 to 1.54; two RCTs, 327 women; moderate-quality evidence). With respect to awareness of prolapse, findings were inconsistent. One RCT found no evidence of a difference between groups at 24 months (OR 1.07, 95% CI 0.61 to 1.87; one RCT, 305 women; low-quality evidence), and a second small RCT reported symptom reduction from the Pelvic Organ Prolapse Symptom Questionnaire completed by the intervention group at 12 months (mean difference (MD) -3.90, 95% CI -6.11 to -1.69; one RCT, 27 women; low-quality evidence). Researchers found no clear differences between groups at 24-month follow-up in rates of repeat surgery (or pessary) for prolapse (OR 1.92, 95% CI 0.74 to 5.02; one RCT, 316 women; low-quality evidence). Other interventions Single RCTs evaluated the following interventions: preoperative guided imagery (N = 44); injection of vasoconstrictor agent at commencement of vaginal prolapse surgery (N = 76); ureteral stent placement during uterosacral ligament suspension (N = 91); vaginal pack (N = 116); prophylactic antibiotics for women requiring postoperative urinary catheterisation (N = 159); and postoperative vaginal dilators (N = 60). Two RCTs evaluated bowel preparation (N = 298), and four RCTs assessed the method and timing of postoperative catheterisation (N = 514) - all in different comparisons. None of these studies reported our primary review outcomes. One study reported intraoperative blood loss and suggested that vaginal injection of vasoconstrictors at commencement of surgery may reduce blood loss by a mean of about 30 mL. Another study reported intraoperative ureteral injury and found no clear evidence that ureteral stent placement reduces ureteral injury. Three RCTs reported postoperative urinary tract infection and found no conclusive evidence that rates of urinary tract infection were influenced by use of a vaginal pack, prophylactic antibiotics, or vaginal dilators. Other studies did not report these outcomes. There was a paucity of data about perioperative interventions in pelvic organ prolapse surgery. A structured programme of pelvic floor muscle training before and after prolapse surgery did not consistently demonstrate any benefit for the intervention; however, this finding is based on the results of two small studies. With regard to other interventions (preoperative bowel preparation and injection of vasoconstrictor agent, ureteral stent placement during uterosacral ligament suspension, postoperative vaginal pack insertion, use of vaginal dilators, prophylactic antibiotics for postoperative catheter care), we found no evidence regarding rates of recurrent prolapse and no clear evidence that these interventions were associated with clinically meaningful reductions in adverse effects, such as intraoperative or postoperative blood transfusion, intraoperative ureteral injury, or postoperative urinary tract infection.

Cochrane review authors evaluated randomised controlled trials (RCTs) that compared prolapse surgery with and without any perioperative (before, during, or after) interventions. The evidence is current to 30 November 2017. Reviewers included 15 trials that evaluated eight different interventions related to prolapse surgery. Although primary outcomes of the review were objective failure (recurrence of prolapse on examination) and awareness of prolapse, reviewers also measured adverse effects, focusing on intraoperative blood loss, intraoperative ureteral injury, postoperative urinary tract infection, and repeat surgery. Key results Reviewers found very little evidence on perioperative interventions in pelvic organ prolapse surgery. Few trials reported primary outcomes. A structured programme of pelvic floor muscle training before and after surgery did not consistently demonstrate any benefit for the intervention. With regard to other preoperative interventions, neither bowel preparation nor detailed preoperative mapping demonstrated significant benefit when compared to usual care. Intraoperative interventions such as injection of a vasoconstrictor agent, ureteral stent placement during uterosacral ligament suspension, or placement of a vaginal pack did not demonstrate benefit for reduced blood loss or rate of urinary tract infection or injury to the ureter. Vaginal packing postoperatively did not reduce the rate of haematoma (collection of blood) when compared to prolapse surgery without packing in a single trial. The rate of postoperative urinary tract infection was not reduced by use of a vaginal pack, prophylactic antibiotics, or vaginal dilators. Quality of the evidence The quality of the evidence ranged from very low to moderate. The main limitation was imprecision, associated with small sample sizes and low event rates.

10.1002/14651858.CD013105

cochrane-simplification-train-1060

cochrane-simplification-train-1060

Three trials with 392 participants met the inclusion criteria. Studies were conducted in three European countries (Switzerland, Netherlands, and Germany). The median age of participants ranged from 62 to 66 years; 53% to 64% were female. Inclusion criteria differed among studies. One trial included participants with Hinchey I characteristics as well as those who underwent Hartmann’s procedure; the second trial included only participants with "a proven stage II/III disease according to the classification of Stock and Hansen"; the third trial considered for inclusion patients with "diverticular disease of sigmoid colon documented by colonoscopy and 2 episodes of uncomplicated diverticulitis, one at least being documented with CT scan, 1 episode of complicated diverticulitis, with a pericolic abscess (Hinchey stage I) or pelvic abscess (Hinchey stage II) requiring percutaneous drainage." We determined that two studies were at low risk of selection bias; two that reported considerable dropouts were at high risk of attrition bias; none reported blinding of outcome assessors (unclear detection bias); and all were exposed to performance bias owing to the nature of the intervention. Available low-quality evidence suggests that laparoscopic surgical resection may lead to little or no difference in mean hospital stay compared with open surgical resection (3 studies, 360 participants; MD -0.62 (days), 95% CI -2.49 to 1.25; I² = 0%). Low-quality evidence suggests that operating time was longer in the laparoscopic surgery group than in the open surgery group (3 studies, 360 participants; MD 49.28 (minutes), 95% CI 40.64 to 57.93; I² = 0%). We are uncertain whether laparoscopic surgery improves postoperative pain between day 1 and day 3 more effectively than open surgery. Low-quality evidence suggests that laparoscopic surgery may improve postoperative pain at the fourth postoperative day more effectively than open surgery (2 studies, 250 participants; MD = -0.65, 95% CI -1.04 to -0.25). Researchers reported quality of life differently across trials, hindering the possibility of meta-analysis. Low-quality evidence from one trial using the Short Form (SF)-36 questionnaire six weeks after surgery suggests that laparoscopic intervention may improve quality of life, whereas evidence from two other trials using the European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) v3 and the Gastrointestinal Quality of Life Index score, respectively, suggests that laparoscopic surgery may make little or no difference in improving quality of life compared with open surgery. We are uncertain whether laparoscopic surgery improves the following outcomes: 30-day postoperative mortality, early overall morbidity, major and minor complications, surgical complications, postoperative times to liquid and solid diets, and reoperations due to anastomotic leak. Results from the present comprehensive review indicate that evidence to support or refute the safety and effectiveness of laparoscopic surgery versus open surgical resection for treatment of patients with acute diverticular disease is insufficient. Well-designed trials with adequate sample size are needed to investigate the efficacy of laparoscopic surgery towards important patient-oriented (e.g. postoperative pain) and health system-oriented outcomes (e.g. mean hospital stay).

We identified three trials that compared the efficacy of laparoscopic surgery and open surgery. These studies included 392 participants (195 in the laparoscopic group vs 197 in the open surgery group). The method used to allocate participants based on randomisation, that is, the choice of treatment that participants received, was determined by a method similar to coin tossing, so the two groups were as similar as possible. We found that laparoscopic surgical resection may lead to little or no difference in mean hospital stay when compared with open surgical resection. Operating time was longer in the laparoscopic group by an average of 49 minutes. No important differences were observed in terms of 30-day postoperative mortality, early overall morbidity, major and minor complications, surgical complications, postoperative times to liquid and solid diets, and reoperations due to anastomotic leak. To assess quality of life, researchers used different scales at different periods of time. Although one trial reported that patients who received laparoscopic surgery had better quality of life, the other two trials showed no benefit favouring either laparoscopic surgery or open surgery. The quality of the evidence varied from low to very low owing to risk of bias (i.e. conclusions may overestimate benefits or underestimate harms because of biased study design and conduct) and limitations in the patient population sample. Well-designed trials are necessary to obtain a more accurate estimate of the benefits and safety of laparoscopic surgery over open surgery.

10.1002/14651858.CD009277.pub2

cochrane-simplification-train-1061

cochrane-simplification-train-1061

We included 15 studies in the review, comprising a total of 1822 adult participants. There are 12 studies awaiting classification, and eight ongoing studies. None of the 15 included studies considered the paediatric population. Four studies were conducted in the abdominal and orthopaedic surgery setting (lumbar spine, or knee and hip replacement), one study in the carotid endarterectomy setting, and the remaining 10 studies in the aortic or cardiac surgery setting. The main sources of bias in the included studies related to potential conflict of interest from industry sponsorship, unclear blinding status or missing participant data. Two studies with 312 participants considered postoperative neurological injury, however no pooled effect estimate could be calculated due to discordant direction of effect between studies (low-quality evidence). One study (N = 126) in participants undergoing major abdominal surgery reported that 4/66 participants experienced neurological injury with blinded monitoring versus 0/56 in the active monitoring group. A second study (N = 195) in participants having coronary artery bypass surgery reported that 1/96 participants experienced neurological injury in the blinded monitoring group compared with 4/94 participants in the active monitoring group. We are uncertain whether active cerebral NIRS monitoring has an important effect on the risk of postoperative stroke because of the low number of events and wide confidence interval (RR 0.25, 95% CI 0.03 to 2.20; 2 studies, 240 participants; low-quality evidence). We are uncertain whether active cerebral NIRS monitoring has an important effect on postoperative delirium because of the wide confidence interval (RR 0.63, 95% CI 0.27 to 1.45; 1 study, 190 participants; low-quality evidence). Two studies with 126 participants showed that active cerebral NIRS monitoring may reduce the incidence of mild postoperative cognitive dysfunction (POCD) as defined by the original studies at one week after surgery (RR 0.53, 95% CI 0.30 to 0.95, I2 = 49%, low-quality evidence). Based on six studies with 962 participants, there was moderate-quality evidence that active cerebral oxygenation monitoring probably does not decrease the occurrence of POCD (decline in cognitive function) at one week after surgery (RR 0.62, 95% CI 0.37 to 1.04, I2 = 80%). The different type of monitoring equipment in one study could potentially be the cause of the heterogeneity. We are uncertain whether active cerebral NIRS monitoring has an important effect on intraoperative mortality or postoperative mortality because of the low number of events and wide confidence interval (RR 0.63, 95% CI 0.08 to 5.03, I2= 0%; 3 studies, 390 participants; low-quality evidence). There was no evidence to determine whether routine use of NIRS-based cerebral oxygenation monitoring causes adverse effects. The effects of perioperative active cerebral NIRS monitoring of brain oxygenation in adults for reducing the occurrence of short-term, mild POCD are uncertain due to the low quality of the evidence. There is uncertainty as to whether active cerebral NIRS monitoring has an important effect on postoperative stroke, delirium or death because of the low number of events and wide confidence intervals. The conclusions of this review may change when the eight ongoing studies are published and the 12 studies awaiting assessment are classified. More RCTs performed in the paediatric population and high-risk patients undergoing non-cardiac surgery (e.g. neurosurgery, carotid endarterectomy and other surgery) are needed.

The evidence is current to December 2016. We updated our search in November 2017, but these results have not yet been incorporated in the review. We included 15 completed randomized controlled trials involving 1822 participants. There are 8 ongoing studies and 12 waiting further assessment. None of the completed studies included infants or children. In four studies participants were undergoing abdominal or orthopaedic surgery, one study included participants undergoing a procedure to restore proper blood flow to the brain, and in the remaining 10 studies participants were undergoing large blood vessel or heart surgery with or without heart bypass. The studies all used cerebral NIRS in the operating room, with only two also using cerebral NIRS in the intensive care unit. The control groups were monitored using methods such as heart rate and mean arterial blood pressure, electroencephalogram, transcranial doppler, bispectral index, oxygen saturation in the jugular vein, evoked potentials or cerebral tissue oxygen partial pressure. Overall, the different studies varied in their approach to the review question. We did not pool (combine) the data for the outcome postoperative neurological injury because of variations between studies. One study with 126 participants having major abdominal surgery reported that 4/66 versus 0/56 participants experienced neurological injury with blinded and active monitoring, respectively. A second study with 195 participants undergoing coronary artery bypass surgery reported that 1/96 versus 4/94 participants suffered neurological injury in the blinded (masked) and active (with active treatments) monitoring groups, respectively. We are unsure whether active NIRS monitoring has an important effect on the risk of postoperative stroke and delirium because there was a low number of events and the result was not precise (2 studies, 240 participants; 1 study, 190 participants, respectively; low-quality evidence). Based on two studies with 126 participants, we found low-quality evidence that cerebral NIRS monitoring may reduce the number of participants with mild cognitive impairment at one week after surgery. Based on six studies with 962 participants, we found moderate-quality evidence that monitoring with cerebral NIRS probably leads to little or no decrease in the number of participants with a decline in cognitive function one week after surgery. We are uncertain whether active cerebral oxygenation monitoring has a crucial effect on intraoperative or postoperative deaths because there was a low number of events and the result was not precise (3 studies, 390 participants; low-quality evidence). We did not find any detrimental effects of the routine use of NIRS-based brain oxygenation monitoring. Overall, it is uncertain whether active NIRS monitoring has a crucial effect on postoperative stroke, delirium or death because of the imprecision of the results (low-quality evidence). Therefore, the effects of active cerebral NIRS monitoring on postoperative nervous system injury, delirium, decline in cognitive function and death are uncertain. For some outcomes, such as postoperative stroke or other neurological injury, the evidence was based on few studies with limited numbers of participants. Reporting of outcomes was often incomplete for all study participants, as was reporting of the study design, such as blinding. Some studies had potential conflicts of interest from industry sponsorship.

10.1002/14651858.CD010947.pub2

cochrane-simplification-train-1062

cochrane-simplification-train-1062

We included a total of 96 studies (10,401 participants) in this review. More than half of the studies (50/96) were carried out in China. Generally the studies were heterogeneous, and many were poorly reported. Physical rehabilitation was found to have a beneficial effect, as compared with no treatment, on functional recovery after stroke (27 studies, 3423 participants; standardised mean difference (SMD) 0.78, 95% confidence interval (CI) 0.58 to 0.97, for Independence in ADL scales), and this effect was noted to persist beyond the length of the intervention period (nine studies, 540 participants; SMD 0.58, 95% CI 0.11 to 1.04). Subgroup analysis revealed a significant difference based on dose of intervention (P value < 0.0001, for independence in ADL), indicating that a dose of 30 to 60 minutes per day delivered five to seven days per week is effective. This evidence principally arises from studies carried out in China. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.003, for independence in ADL). We found physical rehabilitation to be more effective than usual care or attention control in improving motor function (12 studies, 887 participants; SMD 0.37, 95% CI 0.20 to 0.55), balance (five studies, 246 participants; SMD 0.31, 95% CI 0.05 to 0.56) and gait velocity (14 studies, 1126 participants; SMD 0.46, 95% CI 0.32 to 0.60). Subgroup analysis demonstrated a significant difference based on dose of intervention (P value 0.02 for motor function), indicating that a dose of 30 to 60 minutes delivered five to seven days a week provides significant benefit. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.05, for independence in ADL). No one physical rehabilitation approach was more (or less) effective than any other approach in improving independence in ADL (eight studies, 491 participants; test for subgroup differences: P value 0.71) or motor function (nine studies, 546 participants; test for subgroup differences: P value 0.41). These findings are supported by subgroup analyses carried out for comparisons of intervention versus no treatment or usual care, which identified no significant effects of different treatment components or categories of interventions. Physical rehabilitation, comprising a selection of components from different approaches, is effective for recovery of function and mobility after stroke. Evidence related to dose of physical therapy is limited by substantial heterogeneity and does not support robust conclusions. No one approach to physical rehabilitation is any more (or less) effective in promoting recovery of function and mobility after stroke. Therefore, evidence indicates that physical rehabilitation should not be limited to compartmentalised, named approaches, but rather should comprise clearly defined, well-described, evidenced-based physical treatments, regardless of historical or philosophical origin.

We identified 96 studies, up to December 2012, for inclusion in the review. These studies, involving 10,401 stroke survivors, investigated physical rehabilitation approaches aimed at promoting recovery of function or mobility in adult participants with a clinical diagnosis of stroke compared with no treatment, usual care or attention control or in comparisons of different physical rehabilitation approaches. The average number of participants in each study was 105: most studies (93%) included fewer than 200 participants, one study had more than 1000 participants, six had between 250 and 100 participants and 10 had 20 or fewer participants. Outcomes included measures of independence in activities of daily living (ADL), motor function (functional movement), balance, walking speed and length of stay. More than half of the studies (50/96) were carried out in China. These studies showed many differences in relation to the type of stroke and how severe it was, as well as differences in treatment, which varied according to both treatment type and duration. This review brings together evidence confirming that physical rehabilitation (often delivered by a physiotherapist, physical therapist or rehabilitation therapist) can improve function, balance and walking after stroke. It appears to be most beneficial when the therapist selects a mixture of different treatments for an individual patient from a wide range of available treatments. We were able to combine the results from 27 studies (3243 stroke survivors) that compared physical rehabilitation versus no treatment. Twenty-five of these 27 studies were carried out in China. Results showed that physical rehabilitation improves functional recovery, and that this improvement may last long-term. When we looked at studies that compared additional physical rehabilitation versus usual care or a control intervention, we found evidence to show that the additional physical treatment improved motor function (12 studies, 887 stroke survivors), standing balance (five studies, 246 stroke survivors) and walking speed (14 studies, 1126 stroke survivors). Very limited evidence suggests that, for comparisons of physical rehabilitation versus no treatment and versus usual care, treatment that appeared to be effective was given between 30 and 60 minutes per day, five to seven days per week, but further research is needed to confirm this. We also found evidence of greater benefit associated with a shorter time since stroke, but again further research is needed to confirm this. We found evidence showing that no one physical rehabilitation approach was more effective than any other approach. This finding means that physiotherapists should choose each individual patient's treatment according to the evidence available for that specific treatment, and should not limit their practice to a single 'named' approach. It was difficult for us to judge the quality of evidence because we found poor, incomplete or brief reporting of information. We determined that less than 50% of the studies were of good quality, and for most studies, the quality of the evidence was unclear from the information provided.

10.1002/14651858.CD001920.pub3

cochrane-simplification-train-1063

cochrane-simplification-train-1063

We included seven trials (six randomised controlled trials and one quasi-randomised controlled trial) with 704 participants; three of these trials (234 participants) are new to this update. The mean age across the trials was 29 years (range 12 to 90 years), and 82% of the participants were male. All trials compared immobilisation in external rotation (with or without an additional abduction component) versus internal rotation (the traditional method) following closed reduction. No trial evaluated any other interventions or comparisons, such as rehabilitation. All trials provided data for a follow-up of one year or longer; the commonest length was two years or longer. All trials were at some risk of bias, commonly performance and detection biases given the lack of blinding. Two trials were at high risk of selection bias and some trials were affected by attrition bias for some outcomes. We rated the certainty of the evidence as very low for all outcomes. We are uncertain whether immobilisation in external rotation makes a difference to the risk of re-dislocation after 12 months' or longer follow-up compared with immobilisation in internal rotation (55/245 versus 73/243; risk ratio (RR) 0.67, 95% confidence interval (CI) 0.38 to 1.19; 488 participants; 6 studies; I² = 61%; very low certainty evidence). In a moderate-risk population with an illustrative risk of 312 per 1000 people experiencing a dislocation in the internal rotation group, this equates to 103 fewer (95% CI 194 fewer to 60 more) re-dislocations after immobilisation in external rotation. Thus this result covers the possibility of a benefit for each intervention. Individually, the four studies (380 participants) reporting on validated patient-reported outcome measures for shoulder instability at a minimum of 12 months' follow-up found no evidence of a clinically important difference between the two interventions. We are uncertain of the relative effects of the two methods of immobilisation on resumption of pre-injury activities or sports. One study (169 participants) found no evidence of a difference between interventions in the return to pre-injury activity of the affected arm. Two studies (135 participants) found greater return to sports in the external rotation group in a subgroup of participants who had sustained their injury during sports activities. None of the trials reported on participant satisfaction or health-related quality of life. We are uncertain whether there is a difference between the two interventions in the number of participants experiencing instability, defined as either re-dislocation or subluxation (RR 0.84, 95% CI 0.62 to 1.14; 395 participants, 3 studies; very low certainty evidence). Data on adverse events were collected only in an ad hoc way in the seven studies. Reported "transient and resolved adverse events" were nine cases of shoulder stiffness or rigidity in the external rotation group and two cases of axillary rash in the internal rotation group. There were three "important" adverse events: hyperaesthesia and moderate hand pain; eighth cervical dermatome paraesthesia; and major movement restriction between 6 and 12 months. It was unclear to what extent these three events could be attributed to the treatment. The available evidence from randomised trials is limited to that comparing immobilisation in external versus internal rotation. Overall, the evidence is insufficient to draw firm conclusions about whether immobilisation in external rotation confers any benefit over immobilisation in internal rotation. Considering that there are several unpublished and ongoing trials evaluating immobilisation in external versus internal rotation, the main priority for research on this question consists of the publication of completed trials and the completion and publication of ongoing trials. Meanwhile, evaluation of other interventions, including rehabilitation, is warranted. There is a need for sufficiently large, good-quality, well-reported randomised controlled trials with long-term follow-up. Future research should aim to determine the optimal immobilisation duration, precise indications for immobilisation, optimal rehabilitation interventions, and the acceptability of these different interventions.

We identified three new relevant studies in this update. In total, this review now includes seven studies with 704 participants. Most of the participants (82%) were male; the average age across the studies was 29 years (range 12 to 90 years). All of the studies investigated just one comparison: immobilisation in external rotation (when the arm is orientated outwards with the forearm away from the chest) versus immobilisation in internal rotation (the usual sling position, where the arm rests against the chest) following closed reduction. Participants were followed over different lengths of time; the most common duration was two years or longer. We are uncertain whether immobilisation in external rotation makes a difference to the risk of re-dislocation at one-year or more follow-up compared with immobilisation in internal rotation. None of the four studies reporting on patient-reported outcome measures for shoulder instability at a minimum of one-year follow-up found evidence of any important difference between the two interventions. We are uncertain of the relative effects of the two methods of immobilisation on resumption of pre-injury activities or sports. One study found no evidence of a difference between interventions in the return to pre-injury activity of the affected arm. Two other studies found greater return to sports in the external rotation group in a small group of participants who had sustained their injury during sports activities. None of the trials reported on participant satisfaction or health-related quality of life. We are uncertain whether there is a difference between the two interventions in the number of participants experiencing instability, defined as either re-dislocation or subluxation (a partial dislocation). The reporting of adverse events (complications) was unsatisfactory. There were reports of nine cases of short-term shoulder stiffness in the external rotation group and two cases of under-arm rash in the internal fixation group. There were three more serious adverse events: abnormal sensitivity and hand pain; abnormal sensation such as tingling in the little finger and along to the elbow; and major movement restriction. It was unclear to what extent these three adverse events could be attributed to the treatment. We rated the certainty of the evidence as very low for all outcomes. This was mainly because there were not enough data and we were unsure how reliable the results were from the individual studies. Thus we are uncertain about the estimates of effect. Overall, the current evidence is insufficient to inform the choice of immobilisation in external versus internal rotation. There is no evidence to inform on any other conservative interventions following closed reduction of traumatic anterior dislocation of the shoulder.

10.1002/14651858.CD004962.pub4

cochrane-simplification-train-1064

cochrane-simplification-train-1064

We identified 95 studies enrolling over 15,000 women. Compared with placebo or no treatment, the use of prophylactic antibiotics in women undergoing cesarean section reduced the incidence of wound infection (RR 0.40, 95% CI 0.35 to 0.46, 82 studies, 14,407 women), endometritis (RR 0.38, 95% CI 0.34 to 0.42, 83 studies, 13,548 women) and maternal serious infectious complications (RR 0.31, 95% CI 0.20 to 0.49, 32 studies, 6159 women). When only studies that included women undergoing an elective cesarean section were analyzed, there was also a reduction in the incidence of wound infections (RR 0.62, 95% CI 0.47 to 0.82, 17 studies, 3537 women) and endometritis (RR 0.38, 95% CI 0.24 to 0.61, 15 studies, 2502 women) with prophylactic antibiotics. Similar estimates of effect were seen whether the antibiotics were administered before the cord was clamped or after. The effect of different antibiotic regimens was studied and similar reductions in the incidence of infections were seen for most of the antibiotics and combinations. There were no data on which to estimate the effect of maternal administration of antibiotics on infant outcomes. No studies systematically collected and reported on adverse infant outcomes nor the effect of antibiotics on the developing infant immune system. No studies reported on the incidence of oral candidiasis (thrush) in babies. Maternal adverse effects were also rarely described. We judged the evidence for antibiotic treatment compared with no treatment to be of moderate quality; most studies lacked an adequate description of methods and were assessed as being at unclear risk of bias. The conclusions of this review support the recommendation that prophylactic antibiotics should be routinely administered to all women undergoing cesarean section to prevent infection. Compared with placebo or no treatment, the use of prophylactic antibiotics in women undergoing cesarean section reduced the incidence of wound infection, endometritis and serious infectious complications by 60% to 70%. There were few data on adverse effects and no information on the effect of antibiotics on the baby, making the assessment of overall benefits and harms difficult. Prophylactic antibiotics given to all women undergoing elective or non-elective cesarean section is beneficial for women but there is uncertainty about the consequences for the baby.

This review looked at whether antibiotics are effective in preventing infection in women having a cesarean section. It also studied the effect of giving the antibiotics before or after the cord is clamped and different kinds of antibiotics. The review found 95 studies involving over 15,000 women. Routine use of antibiotics at cesarean section reduced the risk of wound and womb infections in mothers as well as the risk of serious complications of infections for the mothers by 60% to 70%. This was so whether the cesarean section was planned (elective) or not, and whether the antibiotics were given before or after clamping of the umbilical cord. The evidence to support antibiotic treatment was of moderate quality but often the way the study was done was not described well enough. None of the studies looked properly at possible adverse effects on the baby and so, although there are benefits for the mother, there is some uncertainty about whether there are any important effects on the baby.

10.1002/14651858.CD007482.pub3

cochrane-simplification-train-1065

cochrane-simplification-train-1065

We included 14 studies with 923 participants in this review. Studies took place in Australia, Canada, the UK, and the USA. Six of the 14 included studies were funded by government agencies and one was funded by a university grant. The rest were funded by charitable foundations or trusts. Each study compared phonics training alone, or in conjunction with one other reading-related skill, to either no training (i.e. treatment as usual) or alterative training (e.g. maths). Participants were English-speaking children or adolescents, of low and middle socioeconomic status, whose reading was one year, one grade, or one standard deviation below the level expected for their age or grade for no known reason. Phonics training varied between studies in intensity (up to four hours per week), duration (up to seven months), training group size (individual and small groups), and delivery (human and computer). We measured the effect of phonics training on seven primary outcomes (mixed/regular word reading accuracy, non-word reading accuracy, irregular word reading accuracy, mixed/regular word reading fluency, non-word reading fluency, reading comprehension, and spelling). We judged all studies to be at low risk of bias for most risk criteria, and used the GRADE approach to assess the quality of the evidence. There was low-quality evidence that phonics training may have improved poor readers' accuracy for reading real and novel words that follow the letter-sound rules (standardised mean difference (SMD) 0.51, 95% confidence interval (CI) 0.13 to 0.90; 11 studies, 701 participants), and their accuracy for reading words that did not follow these rules (SMD 0.67, 95% CI 0.26 to 1.07; 10 studies, 682 participants). There was moderate-quality evidence that phonics training probably improved English-speaking poor readers' fluency for reading words that followed the letter-sounds rules (SMD 0.45, 95% CI 0.19 to 0.72; 4 studies, 224 participants), and non-word reading fluency (SMD 0.39, 95% CI 0.10 to 0.68; 3 studies, 188 participants), as well as their accuracy for reading words that did not follow these rules (SMD 0.84, 95% CI 0.30 to 1.39; 4 studies, 294 participants). In addition, there was low-quality evidence that phonics training may have improved poor readers' spelling (SMD 0.47, 95% CI –0.07 to 1.01; 3 studies, 158 participants), but only slightly improve their reading comprehension (SMD 0.28, 95% CI –0.07 to 0.62; 5 studies, 343 participants). Phonics training appears to be effective for improving literacy-related skills, particularly reading fluency of words and non-words, and accuracy of reading irregular words. More studies are needed to improve the precision of outcomes, including word and non-word reading accuracy, reading comprehension, spelling, letter-sound knowledge, and phonological output. More data are also needed to determine if phonics training in English-speaking poor readers is moderated by factors such as training type, intensity, duration, group size, or administrator.

The search, updated in May 2018, identified 14 studies that tested phonics training in 923 English-speaking poor readers. The studies took place in Australia, Canada, the UK, and the USA. Six of the 14 included studies were funded by government agencies and one was funded by a university grant. The rest were funded by charitable foundations or trusts. Each study compared phonics training alone, or with one other reading-related skill, to either no training (i.e. treatment as usual) or alterative training (e.g. maths). Participants were English-speaking children or adolescents, of low and middle socioeconomic status, whose reading was one year, one grade, or one standard deviation (distance from the average) below the level expected for their age or grade for no known reason. Phonics training varied between studies in frequency (up to four hours per week), duration (up to seven months), training group size (individual and small groups), and delivery (human and computer). We measured the effect of phonics training on poor readers' ability to read words and novel words (non-words) accurately and fluently, as well as their comprehension of text, and their knowledge of letter-sound rules (letter-sound knowledge) and speech sounds (phonological output). We found that phonics training in English-speaking poor readers probably improved irregular word reading accuracy, mixed/regular word reading fluency, and non-word reading fluency. It may also have improved mixed/regular word reading accuracy, non-word reading accuracy, reading comprehension, spelling, letter-sound knowledge, and phonological output. The overall quality of the evidence ranged from low to moderate. This was primarily due to large differences in the size of phonics-training effects between studies. More studies are needed to improve the precision of the outcomes. The evidence suggests that phonics training can improve literacy in English-speaking poor readers. The positive effects of phonics training on all reading-related outcomes suggests that phonics training is not harmful for poor readers.

10.1002/14651858.CD009115.pub3

cochrane-simplification-train-1066

cochrane-simplification-train-1066

Four trials (involving a total of 269 participants) were included. The participants were children with cystic fibrosis and their parents or caregivers in three trials and adults with cystic fibrosis in one trial. The trials compared four different self-management education interventions versus standard treatment: (1) a training programme for managing cystic fibrosis in general; (2) education specific to aerosol and airway clearance treatments; (3) disease-specific nutrition education; and (4) general and disease-specific nutrition education. Training children to manage cystic fibrosis in general had no statistically significant effects on weight after six to eight weeks, mean difference -7.74 lb (i.e. 3.51 kg) (95% confidence interval -35.18 to 19.70). General and disease-specific nutrition education for adults had no statistically significant effects on: pulmonary function (forced expiratory volume at one second), mean difference -5.00 % (95% confidence interval -18.10 to 8.10) at six months and mean difference -5.50 % (95% confidence interval -18.46 to 7.46) at 12 months; or weight, mean difference - 0.70 kg (95% confidence interval -6.58 to 5.18) at six months and mean difference -0.70 kg (95% confidence interval -6.62 to 5.22) at 12 months; or dietary fat intake scores, mean difference 1.60 (85% confidence interval -2.90 to 6.10) at six months and mean difference 0.20 (95% confidence interval -4.08 to 4.48) at 12 months. There is some limited evidence to suggest that self-management education may improve knowledge in patients with cystic fibrosis but not in parents or caregivers. There is also some limited evidence to suggest that self-management education may result in positively changing a small number of behaviours in both patients and caregivers. The available evidence from this review is of insufficient quantity and quality to draw any firm conclusions about the effects of self-management education for cystic fibrosis. Further trials are needed to investigate the effects of self-management education on a range of clinical and behavioural outcomes in children, adolescents and adults with cystic fibrosis and their caregivers.

We set out to review the effects of self-management education for cystic fibrosis on a range of health outcomes in individuals of all ages with cystic fibrosis and their caregivers. Our search for available evidence identified four trials, and all four compared a form of self-management education to standard treatment. The precise focus of self management differed between trials and included a training programme for managing cystic fibrosis, education on chest treatments, education on nutrition specific to cystic fibrosis, and education on general and disease-specific nutrition. Self-management education had no positive effects on lung function, weight, or intake of fatty food. There is some evidence to suggest that self-management education improves knowledge about cystic fibrosis and its management in patients with this condition and some self-management behaviours in patients and caregivers. However, due to the small number of trials in this review, and because of concerns about the quality of these trials, we are unable to reach any firm conclusions about the effects of self-management education for cystic fibrosis. We recommend that further trials are conducted to evaluate the effects of self-management education interventions.

10.1002/14651858.CD007641.pub3

cochrane-simplification-train-1067

cochrane-simplification-train-1067

This updated review includes a total of 24 studies (six cross-over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design) with a total of 4473 participants. Ten studies were included in the 2008 update, and 14 studies have been added to this update. Thirteen studies (2380 participants) evaluated cranberry juice/concentrate; nine studies (1032 participants) evaluated cranberry tablets or capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were not included in the meta-analyses because either the design was a cross-over study and data were not reported separately for the first phase, or there was a lack of relevant data. Data included in the meta-analyses showed that, compared with placebo, water or not treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04) or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20). Overall heterogeneity was moderate (I² = 55%). The effectiveness of cranberry was not significantly different to antibiotics for women (RR 1.31, 95% CI 0.85, 2.02) and children (RR 0.69 95% CI 0.32 to 1.51). There was no significant difference between gastrointestinal adverse effects from cranberry product compared to those of placebo/no treatment (RR 0.83, 95% CI 0.31 to 2.27). Many studies reported low compliance and high withdrawal/dropout problems which they attributed to palatability/acceptability of the products, primarily the cranberry juice. Most studies of other cranberry products (tablets and capsules) did not report how much of the 'active' ingredient the product contained, and therefore the products may not have had enough potency to be effective. Prior to the current update it appeared there was some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. The addition of 14 further studies suggests that cranberry juice is less effective than previously indicated. Although some of small studies demonstrated a small benefit for women with recurrent UTIs, there were no statistically significant differences when the results of a much larger study were included. Cranberry products were not significantly different to antibiotics for preventing UTIs in three small studies. Given the large number of dropouts/withdrawals from studies (mainly attributed to the acceptability of consuming cranberry products particularly juice, over long periods), and the evidence that the benefit for preventing UTI is small, cranberry juice cannot currently be recommended for the prevention of UTIs. Other preparations (such as powders) need to be quantified using standardised methods to ensure the potency, and contain enough of the 'active' ingredient, before being evaluated in clinical studies or recommended for use.

This review identified 24 studies (4473 participants) comparing cranberry products with control or alternative treatments. There was a small trend towards fewer UTIs in people taking cranberry product compared to placebo or no treatment but this was not a significant finding. Many people in the studies stopped drinking the juice, suggesting it may not be an acceptable intervention. Cranberry juice does not appear to have a significant benefit in preventing UTIs and may be unacceptable to consume in the long term. Cranberry products (such as tablets or capsules) were also ineffective (although had the same effect as taking antibiotics), possibly due to lack of potency of the 'active ingredient'.

10.1002/14651858.CD001321.pub5

cochrane-simplification-train-1068

cochrane-simplification-train-1068

Ten efficacy trials of SPf66 involving 9698 participants were included. Results with SPf66 in reducing new episodes of P. falciparum malaria were heterogeneous: it was not effective in four African trials (RR 0.98, 95% CI 0.90 to 1.07; 2371 participants) or in one Asian trial (RR 1.06, 95% CI 0.90 to 1.25; 1221 participants). In four trials in South America the number of first attacks with P. falciparum was reduced by 28% (RR 0.72, 95% CI 0.63 to 0.82; 3807 participants). It did not reduce episodes of P. vivax malaria or admission to hospital with severe malaria. Trials have not indicated any serious adverse events with SPf66 vaccine. There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in South America. There is no justification for further trials of SPf66 in its current formulation. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified.

SPf66 has had 10 trials in Africa, Asia, and South America. Results were initially promising, but further trials showed only a small effect in some trials, and no effect in Africa. There is no evidence that SPf66 is effective enough to be introduced on a routine basis for prevention of malaria.

10.1002/14651858.CD005966

cochrane-simplification-train-1069

cochrane-simplification-train-1069

We found three trials which met our inclusion criteria, covering 1567 smokers (cessation: STRATUS-EU and STRATUS-US), and 1661 quitters (relapse prevention: STRATUS-WW). At one year, the pooled risk ratio (RR) for quitting with rimonabant 20 mg was 1.50 (95% confidence interval (CI) 1.10 to 2.05). No significant benefit was demonstrated for rimonabant at 5 mg dosage. Adverse events included nausea and upper respiratory tract infections. In the relapse prevention trial, smokers who had quit on the 20 mg regimen were more likely to remain abstinent on either active regimen than on placebo; the RR for the 20 mg maintenance group was 1.29 (95% CI 1.06 to 1.57), and for the 5 mg maintenance group 1.30 (95% CI 1.06 to 1.59). There appeared to be no significant benefit of maintenance treatment for the 5 mg quitters. One trial of taranabant was not included in our meta-analyses, as it followed participants only until end of treatment; at eight weeks it found no benefit for treatment over placebo, with an OR of 1.2 (90% CI 0.6 to 2.5). For rimonabant, weight gain was reported to be significantly lower among the 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight, while normal weight smokers did not. For taranabant, weight gain was significantly lower for 2-8 mg versus placebo at the end of eight weeks of treatment. In 2008, post-marketing surveillance led the European Medicines Agency (EMEA) to require Sanofi Aventis to withdraw rimonabant, because of links to mental disorders. The development of taranabant was also suspended by Merck & Co because of unacceptable adverse events. From the trial reports available, rimonabant 20 mg may increase the chances of quitting approximately 1½-fold. The evidence for rimonabant in maintaining abstinence is inconclusive. Rimonabant 20 mg may moderate weight gain in the long term. Taranabant 2-8 mg may moderate weight gain, at least in the short term. In 2008, development of both rimonabant and taranabant was discontinued by the manufacturers.

We searched our own specialised register of controlled trials. We also contacted Sanofi Aventis, the manufacturers of rimonabant, and researchers who presented early findings at conferences. We found two randomized controlled trials (RCTs) of rimonabant for smoking cessation, covering 1567 smokers, and one RCT of rimonabant for relapse prevention covering 1661 quitters. The available information shows that rimonabant at the 20 mg dose increased by 1½-fold the chances of not smoking at one year, compared with placebo. Rimonabant 5 mg did no better than placebo at any time point. In the relapse prevention trial, smokers who quit successfully with rimonabant 20 mg were 1½ times more likely to remain abstinent on active treatment (5 mg or 20 mg for 42 weeks) than on placebo. For those who quit successfully on 5 mg, neither active nor placebo treatment appeared to benefit them in avoiding relapse. This inconsistent picture makes it difficult to find a clear benefit for rimonabant in preventing relapse. One trial of taranabant (317 smokers) did not find a benefit for treatment over placebo, and the taranabant group suffered more side effects than the placebo group. Main side effects for rimonabant included nausea and upper respiratory tract infections, and serious harms were reported to be low. For taranabant, the main side effects included problems with digestive, nervous, psychiatric, skin and blood vessel organ systems. For both drugs, the number and severity of the side effects increased in those taking higher doses. Although the evidence on weight change is sparse in these trials, weight gain was reported to be significantly lower among the rimonabant 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight on 20 mg, while normal weight smokers did not. Taranabant also limited weight gain during cessation attempts. In 2008 both rimonabant and taranabant were withdrawn by the manufacturers, because of links to mental disorders and unacceptable side effects.

10.1002/14651858.CD005353.pub4

cochrane-simplification-train-1070

cochrane-simplification-train-1070

This is an update of a 2001 review that identified no eligible trials. One trial including 40 infants met the inclusion criteria for this review. Using GRADE criteria, we judged the quality of the evidence as low owing to risk of bias (inadequate reporting of methods of randomisation, allocation concealment and/or blinding) and imprecision (wide confidence intervals and data from a single small trial). We found no evidence of a difference between calcium and phosphorus supplementation versus no supplementation for neonatal growth outcomes (weight, length, head circumference) at any time point reported (two, four or six weeks postnatal age). At six weeks postnatal age, supplementation with calcium/phosphorus was associated with a decrease in serum alkaline phosphatase concentration (MD -56.85 IU/L, 95% CI -101.27 to -12.43; one randomised controlled trial (RCT); n = 40 infants). Investigators provided no data on growth at 12 to 18 months, neonatal fractures, feed intolerance, breastfeeding or any of the prespecified childhood outcomes for this review (fractures, growth, neurodevelopmental outcomes). We identified one small trial including only 40 infants that compared supplementation of human milk with calcium and phosphorus versus no supplementation in hospitalised preterm infants. We judged the evidence to be of low quality and found no evidence of differences between groups for clinically important outcomes including growth and fractures. Although serum alkaline phosphatase concentration was reduced in the group receiving supplementation at six weeks postnatal age, this difference is unlikely to be of clinical significance. We conclude that evidence is insufficient to determine whether benefit or harm ensues when human milk is supplemented with calcium and/or phosphorus for the hospitalised preterm infant. We see no advantage of conducting further trials of this intervention because with the advent of multi-component human milk fortifier, supplementation of human milk with calcium and/or phosphorus alone is no longer common practice. Future trials should consider assessing effects of multi-component fortifiers with different mineral compositions on clinically important outcomes during the neonatal period and in later childhood.

We searched for evidence in April 2016 and identified one randomised controlled trial including 40 babies. Investigators reported a small decrease in the concentration of alkaline phosphatase (an enzyme involved in bone growth) among infants who had received calcium/phosphorus supplementation. We found no difference in growth between infants who had been given human milk supplemented with extra calcium and phosphorus and infants who had received no supplementation. One small trial provided the evidence, and we judged the evidence to be of low quality. Researchers reported no follow-up of these babies into childhood. Evidence is insufficient to allow a judgement as to whether extra calcium and/or phosphorus provided to preterm babies confers benefit for their bones and growth. It is no longer very common to give calcium and phosphorus supplements alone, as human milk fortifiers now available include many other components as well as minerals to support the growth and development of preterm babies. We therefore suggest that future trials conducted to examine effects of mineral supplements in preterm babies include them in multi-component human milk fortifiers and assess clinically important outcomes into childhood.

10.1002/14651858.CD003310.pub2

cochrane-simplification-train-1071

cochrane-simplification-train-1071

There were a total of 19 trials that met inclusion criteria and that had data sufficient for analysis. Thirteen trials reported sufficient information to use a global rating of improvement and nine trials provided information on a comprehensive rating scale. Three trials provided both outcome measures. It was not possible to use many of the published results in a combined analysis owing to the lack of sufficient data to perform statistical analyses. For the 12 trials that used global ratings, there was a significant effect favouring hydergine (OR 3.78, 95% CI, 2.72 to 5.27). For the nine trials that used comprehensive ratings, there was a significant mean difference favouring hydergine (WMD 0.96, 95%CI, 0.54 to 1.37). Hydergine was well tolerated in these trials, with 78% of randomized subjects available for data analyses. Greater effect sizes on global ratings were associated with younger age, and possibly higher dose, although most of the subgroup analyses were statistically insignificant. As in an earlier systematic review, we found hydergine to show significant treatment effects when assessed by either global ratings or comprehensive rating scales (based here on a smaller set of trials than in the earlier published systematic review because trials were required to have data that could conform with MetaView, the Cochrane Collaboration statistics software). The small number of trials available for analysis, however, limited the ability of subgroup analyses to identify statistically significant moderating effects. Unfortunately, most of the randomized, double-blind, and placebo-controlled trials of hydergine were conducted and published before the advent of consensus-based diagnostic standards of dementia in 1984; therefore diagnostic criteria were less specific. As a result, uncertainty remains regarding hydergine's efficacy in dementia.

The statistical evidence for efficacy in 'possible or probable Alzheimer's disease' patients was so modest however that one additional statistically non-significant trial would have reduced the results to non significance; evidence for efficacy in vascular dementia rested on relatively stronger effects for hydergine on clinical ratings; and effective doses may be higher than 3 mg/d (i.e., than that currently approved in the USA). Despite its availability for 40 years, the circumstances of hydergine's efficacy in dementia syndromes have not been adequately researched, and have yet to be precisely defined.

10.1002/14651858.CD000359

cochrane-simplification-train-1072

cochrane-simplification-train-1072

We included three RCTs in the review, randomising a total of 161 overweight and obese women with endometrial cancer. All studies compared combined behavioural and lifestyle interventions to facilitate weight loss through dietary modification and increased physical activity. The included RCTs were of low or very low quality, due to high risk of bias by failing to blind participants, personnel and outcome assessors, and significant loss to follow-up (attrition rate up to 29%). Combined behaviour and lifestyle interventions were not associated with improved overall survival (risk ratio (RR mortality), 0.23 95% confidence interval (CI) 0.01 to 4.55, P = 0.34, one RCT, 37 participants; very low-certainty evidence) compared with usual care at 24 months. There was no evidence that such interventions were associated with improvements in cancer-specific survival or cardiovascular event frequency as no cancer-related deaths, myocardial infarctions or strokes were reported in the included studies. None of the included RCTs reported data for the outcome of recurrence-free survival. Combined behaviour and lifestyle interventions were not associated with significant weight loss at either six months (mean difference (MD) -1.88 kg, 95% CI -5.98 to 2.21 kg, P = 0.37, three RCTs, 131 participants, I2= 0%; low-certainty evidenc e)or 12 months (MD -8.98 kg, 95% CI -19.88 to 1.92 kg, P = 0.11, two RCTs, 91 participants, I2= 0%; very low-certainty evidence) when compared with usual care. Combined behaviour and lifestyle interventions were not associated with increased quality of life, when measured using either the SF-12 Physical Health questionnaire or FACT-G at six months (FACT-G MD 2.51, 95% CI -5.61 to 10.64, P = 0.54, two RCTs, 95 participants, I2= 83%; very low-certainty evidence), or by FACT-G alone at 12 months (MD 2.77, 95% CI -0.65 to 6.20, P = 0.11, two RCTs, 89 participants, I2= 0%; very low-certainty evidence) when compared with usual care. No serious adverse events, for example hospitalisation or deaths, were reported in included trials. Lifestyle and behavioural interventions were associated with a higher risk of musculoskeletal symptoms (RR 19.03, 95% CI 1.17, 310.52, P = 0.04, two RCTs, 91 participants; low-certainty evidence). There is currently insufficient high-quality evidence to determine the effect of combined lifestyle and behavioural interventions on survival, quality of life, or significant weight loss in women with a history of endometrial cancer compared to those receiving usual care. The limited evidence suggests that there is little or no serious or life-threatening adverse effects due to these interventions, although musculoskeletal problems were increased, presumably due to increased activity levels. Our conclusion is based on low- and very low-quality evidence from a small number of trials and very few patients. We therefore have very little confidence in the evidence: the true effect of weight-loss interventions in obese women with endometrial cancer is currently not known. Further methodologically-rigorous, adequately-powered RCTs are required with follow-up of 5 to 10 years duration. These should focus on the effects of varying dietary modification regimens, pharmacological treatments associated with weight loss and bariatric surgery on survival, quality of life, weight loss and adverse events.

We included three randomised controlled trials in which women were allocated at random to receive one of several interventions (treatments) and which involved 161 obese participants. The trials were conducted in the USA and the UK. All compared lifestyle advice (diet and exercise) plus self-help techniques (to encourage adherence to the advice) with usual care. The evidence is current to January 2018. We found no benefit for endometrial cancer survivors from receiving lifestyle advice in terms of survival, cardiovascular events or quality of life, though such interventions were not associated with significant or serious harms to participants. They did, however, report higher rates of musculoskeletal symptoms, presumably due to increases in physical activity. Whilst some women lost weight with these interventions, others did not, meaning that overall there was little or no benefit. The quality of included studies was, however, low or very low and all were small in terms of the number of participants and not designed to specifically look at the effect of their intervention on survival. Additional high-quality studies are required in this field and currently there are five ongoing trials.

10.1002/14651858.CD012513.pub2

cochrane-simplification-train-1073

cochrane-simplification-train-1073

We included 43 studies that met our inclusion criteria in this updated review out of 88 potentially eligible studies. The studies included a large polyclonal IVIG trial in neonates that was concluded in 2011 and classified as ongoing in the 2010 version of this review. Pooled analysis of polyclonal and monoclonal IVIG was not done due to clinical heterogeneity. Subgroup analysis of 10 polyclonal IVIG trials (n = 1430) and seven trials on IgM-enriched polyclonal IVIG (n = 528) showed significant reductions in mortality in adults with sepsis compared to placebo or no intervention (relative risk (RR) 0.81; 95% confidence interval (CI) 0.70 to 0.93 and RR 0.66; 95% CI 0.51 to 0.85, respectively). Subgroup analysis of polyclonal IVIG in neonates, which now includes the recently concluded large polyclonal IVIG trial, showed no significant reduction in mortality for standard IVIG (RR 1.00; 95% CI 0.92 to 1.08; five trials, n = 3667) and IgM-enriched polyclonal IVIG (RR 0.57; 95% CI 0.31 to 1.04; three trials, n = 164). Sensitivity analysis of trials with low risk of bias showed no reduction in mortality with polyclonal IVIG in adults (RR 0.97; 95% CI 0.81 to 1.15; five trials, n = 945) and neonates (RR 1.01; 95% CI 0.93 to 1.09; three trials, n = 3561). Mortality was not reduced among patients (eight trials, n = 4671) who received anti-endotoxin antibodies (RR 0.99; 95% CI 0.91 to1.06) while anti-cytokines (nine trials, n = 7893) demonstrated a marginal reduction in mortality (RR 0.92; 95% CI 0.86 to 0.97). Polyclonal IVIG reduced mortality among adults with sepsis but this benefit was not seen in trials with low risk of bias. Among neonates with sepsis, there is sufficient evidence that standard polyclonal IVIG, as adjunctive therapy, does not reduce mortality based on the inclusion of the large polyclonal IVIG trial on neonates. For Ig-M enriched IVIG, the trials on neonates and adults were small and the totality of the evidence is still insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.

Sepsis is the inflammatory response of the body to severe infection, which can be caused by a variety of micro-organisms including bacteria, viruses and fungi. Signs of sepsis include fever, hypothermia, rapid heart rate and respiration; and a laboratory finding of increased or decreased white blood cell count. Deaths as a result of sepsis and septic shock remain high despite giving antibiotics, especially if the functions of a persons's vital organs such as the lungs, heart and kidneys are affected. Several studies have looked into other agents than antibiotics to help the body fight the effects of sepsis. Intravenous immunoglobulin preparations contain antibodies that help the body to neutralize bacterial toxins. There are two types of preparations. These are polyclonal immunoglobulins that contain several antibodies directed at endotoxin and inflammatory mediators, and monoclonal immunoglobulins which target a specific inflammatory mediator or antigen. Intravenous immunoglobulins are blood products, specifically pooled sera derived from human donor blood. For this updated Cochrane review, we searched the medical literature databases to January 2012. We included 43 randomized controlled trials (RCTs); 25 were RCTs of polyclonal intravenous immunoglobulins (IVIGs) with 17 in adults (1958 participants) and eight in newborn infants (3831 participants) including a large polyclonal IVIG trial on infants with sepsis that was published in 2011. The remaining 18 trials (a total of 13,413 participants) were of monoclonal antibodies. Both standard and immunoglobulin M (IgM)-enriched polyclonal immunoglobulins decreased the number of deaths in adults but not in infants. However, no reductions in adult deaths were seen with polyclonal IVIG using high quality trials only. Among newborn infants with sepsis, there is definitive evidence that standard polyclonal IVIG does not reduce the number of deaths. In the monoclonal immunoglobulin trials, anti-endotoxin antibodies showed no benefit while the anti-cytokines showed a very small reduction in deaths among adults with sepsis. The polyclonal immunoglobulin trials in adults were small compared to the trials of monoclonal agents. The reduction in deaths observed with polyclonal IgM-enriched preparations as add-on therapy for sepsis needs to be confirmed in large studies that use high quality methods.

10.1002/14651858.CD001090.pub2

cochrane-simplification-train-1074

cochrane-simplification-train-1074

We included three trials with a total of 420 children; there were no trials in adult populations. The largest of the three trials was conducted in settings with high mortality rates and was judged to have low risk of bias for all domains, except performance bias which was high risk. The other two smaller trials were not of high quality.The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% confidence interval (CI) 0.53 to 1.27; 407 participants; low quality of evidence) or acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08; 407 participants; low quality of evidence). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group for spasticity (RR 0.50, 95% CI 0.27 to 0.93; 357 participants); and seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83; 357 participants) and 14 days (RR 0.19, 95% CI 0.04 to 0.88; 357 participants). There was very low quality of evidence favouring maintenance fluid over restrictive fluid for chronic severe neurological sequelae at three months follow-up (RR 0.42, 95% CI 0.20 to 0.89; 351 participants). The quality of evidence regarding fluid therapy in children with acute bacterial meningitis is low to very low and more RCTs need to be conducted. There is insufficient evidence to guide practice as to whether maintenance fluids should be chosen over restricted fluids in the treatment of acute bacterial meningitis.

The evidence is current to March 2016. We did not find any trials in adult populations and included three trials involving 420 children. All trials were set in countries where death rates for meningitis are high. In one study no funding source was mentioned. The remaining two studies were funded jointly by pharmaceutical concerns with government agencies and a charitable agency. No studies reported important healthcare outcomes such as duration of hospital stay, raised intracranial pressure, or status epilepticus. An adverse effect in children with restricted fluid intake was that they were less likely to have low levels of sodium in their blood and therefore they would experience greater reductions in body fluids. An adverse effect of unrestricted fluid administration was reported in one study as short-term swelling of the face and low blood sodium levels one to two days after fluids were started, although the largest study found no difference in blood sodium levels. Quality of the evidenceAnalysis of available trials found low quality evidence that there is no significant difference between maintenance versus restrictive fluid regimens for the outcome of death and acute severe neurological complications. There was also some evidence favouring maintenance fluid therapy over restricted fluids for chronic severe neurological events at three months follow-up, but the quality was very low.

10.1002/14651858.CD004786.pub5

cochrane-simplification-train-1075

cochrane-simplification-train-1075

A total of 4092 titles were screened and 14 full text reports reviewed; a single small study met the inclusion criteria. In the included RCT, 40 women (35 with ovarian cancer) had extensive elective surgery including bowel resection for treatment of gynaecological malignancy. Randomisation was made to either early oral feeding (oral fluids in the first 24 hours, solid foods on the following day) or to a 'traditional' feeding regimen where oral fluids and foods were delayed until there was evidence of bowel function. Most women in the early feeding group (14/18) were able to resume eating solid food one day after surgery. This resulted in a significantly shorter hospital stay with no increase in postoperative complications or change in quality of life measures in comparison with the women on the 'traditional' feeding regimen. The incidence of nausea and vomiting during the postoperative stay was similar in both groups and was noted in slightly more than half of the women. Overall survival was evaluated until 30 days following discharge from hospital; in this period, there was one death of a woman who had been in the 'traditional oral feeding' group, cause of death was not noted. We assessed risk of bias and found no high risk of bias was identified in the methodology and reporting of the included study, although there was an increased risk of bias due to the small size of the study in which not all of the women had ovarian cancer. Although women with ovarian cancer have been shown to be at risk of malnutrition, there is a lack of evidence derived from RCTs evaluating the identification, assessment and treatment of malnutrition during the perioperative phase of treatment. There is evidence from one small study that some women with ovarian cancer undergoing surgery with associated bowel resection may safely commence oral fluids within 24 hours of surgery and solid foods on the following day. Further research is required, including a RCT, to generate guidance concerning the treatment of malnutrition in this patient group.

In this review, the authors looked for studies (randomised controlled trials (RCTs)) from around the world to find out how women with ovarian cancer were assessed to see if they were eating and drinking well and what help they may be given with nutrition before or after surgery. A lack of information was found on this topic. One RCT was found where a small group of women (40 including 35 with ovarian cancer) requiring extensive elective surgery for gynaecological cancer including surgery to the gut, were able to restart eating normal foods on the day after surgery. They were able to leave hospital earlier and did not have more complications in the month after surgery than women who were not allowed to resume eating normal foods until at least three days after the operation. More studies are needed to confirm whether restarting normal eating one day after surgery can be recommended for women having surgery for ovarian cancer. More research is needed to provide information about how to identify and treat problems of malnutrition in women with ovarian cancer.

10.1002/14651858.CD009884.pub2

cochrane-simplification-train-1076

cochrane-simplification-train-1076

One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases. We are very uncertain about the effects of TES on bowel movements, colonic transit, soiling symptoms and quality of life due to high risk of bias, indirectness and imprecision. For our outcomes of interest the 95% CI of most analysis results include potential benefit and no effect. There is insufficient evidence to determine the effect of TES on bowel movements and colonic transit. The study reported that 16/21 children in the TES group and 15/21 in the sham group had > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53; very low-quality evidence). Ten out of 14 children in the TES group had improved colonic transit compared to 1/7 in the sham group (RR 5.00, 95% CI 0.79 to 31.63; very low-quality evidence). Mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants; very low-quality evidence). The radiological assessment of colonic transit outcomes means that these results might not translate to important improvement in clinical symptoms or increased bowel movements. There is insufficient evidence to determine the effect of TES on symptoms and quality of life (QoL) outcomes. Nine out of 13 children in the TES group had improved soiling-related symptoms compared to 4/12 sham participants (RR 2.08, 95% CI 0.86 to 5.00; very low-quality evidence). Four out of 8 TES participants reported an improvement in QoL compared to 1/8 sham participants (RR 4.00, 95% CI 0.56 to 28.40; very low-quality evidence). The effects of TES on self-perceived (MD 5.00, 95% CI -1.21 to 11.21; one study, 33 participants; very low-quality evidence) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants; very low-quality evidence) are uncertain. No adverse effects were reported in the included study. The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the efficacy and safety of TES in children with chronic constipation can be drawn. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.

We included a single study with 11 reports that focused on results for different outcomes. The participants of the included study were 46 children aged 8 to 18 years recruited from the clinic of a tertiary hospital in Melbourne, Australia who were diagnosed with long-term constipation either based on their symptoms and/or X-ray studies. The studies divided the patients into two groups, one receiving the actual TES , with electrodes placed on their belly and electrical current running, and the other receiving sham stimulation, with identical device administered but without the electrical current. The participants were followed-up for up to four years, although only outcome information up until the follow-up period of two months were available in this review. The study was funded by the Australian National Health and Medical Research Council and Murdoch Children's Research Institute Theme Investment Grants. There was not enough information on certain aspects of the trial methodologies from the reports gathered, although it was clear that the physiotherapists who administered the TES treatment or sham treatment were aware of which group the patients were allocated to. The knowledge of the participants' allocated group might have influenced the way the actual and sham therapies were administered, as well as the way some of the outcome data, such as symptoms of constipation and soiling and quality of life, might have been reported by the therapist as well as the patients and their carers. This raised concerns regarding the overall methodological quality of the study. The very low quality evidence for all of the results means that we are uncertain about the effects of TES when compared with sham stimulation. Overall, there were no differences between children who received TES and sham stimulation in the number of children with improved complete spontaneous bowel movements, improved bowel movements (as assessed by X-Ray with special contrast), improved symptoms related to soiling and quality of life. There were also no differences between the two groups in the average change in the quality of life scores after the therapy, as assessed by the children themselves as well as their parents. The only difference noted was in mean bowel transit rate, namely, distance travelled by the radioactive substance along the bowel, in which children who received TES had their radioactive substance slightly further down their bowel compared to children who received a sham stimulation. However, it was unclear whether such a difference in distance travelled in the bowel translated to any meaningful differences in defaecation and constipation-related symptoms. No side effects were reported in the study. Overall, this study included a small number of patients and we had concerns regarding the methods resulting in very low quality evidence for all the outcomes assessed. The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the effectiveness and side effects of TES in children with chronic constipation can be drawn. Further studies assessing TES for the management of constipation are needed. We suggest that future research should provide clear documentation on specific methods in the conduct of the trials, and include outcomes that are important for patients, such as spontaneous or complete bowel movements or improvement in constipation-related symptoms along with assessments of quality of life.

10.1002/14651858.CD010873.pub4

cochrane-simplification-train-1077

cochrane-simplification-train-1077

Sixty-five (65) studies were identified for possible inclusion in this review. Fourteen published RCTs with a total of 1551 participants met the inclusion criteria. Duration of cry was significantly reduced in infants who were administered a sweet-tasting solution [MD -13.47 (95% CI -16.80 to -10.15)], P < 0.00001 compared with water. However, there was considerable heterogeneity between the studies (I2 = 94%) that we were unable to explain. Meta-analysis was not able to be undertaken for any of the other outcome measures, except for cry duration, because of differences in study design. However, most of the individual studies that measured pain found sucrose to significantly reduce pain compared with the control group. One study compared sucrose and Lidocaine-prilocaine cream and no significant difference was found between the two treatments for the outcomes pain and cry duration. Due to the differences between the studies, we were unable to identify the optimal concentration, volume or method of administration of sweet-tasting solutions in infants aged one to 12 months. Further large RCTs are needed. There is insufficient evidence to confidently judge the effectiveness of sweet-tasting solutions in reducing needle-related pain in infants (one month to 12 months of age). The treatments do, however, appear promising. Data from a series of individual trials are promising, as are the results from a subset meta-analysis of studies measuring duration of crying. Further well controlled RCTs are warranted in this population to determine the optimal concentration, volume, method of administration, and possible adverse effects.

In this review we were interested in whether giving babies sugar-based solutions to taste when the needle breaks the skin will help reduce their pain. We found 14 separate studies that had asked this question. However, the differences between the studies were often too great to let us combine their findings. Overall, the studies show that different types of sugar-based solutions were effective but we were not able to confidently assert that there is strong evidence for this treatment in reducing pain. We did find some evidence that babies may not cry for as long if given sugar-based solutions. This review is broadly in agreement with two other reviews, one asking this question in younger children, and one in older children. There is a need for better studies in this field.

10.1002/14651858.CD008411.pub2

cochrane-simplification-train-1078

cochrane-simplification-train-1078

The search identified 3659 abstracts, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta-analyses were possible. The main outcome was reduction of severity (response) of depression, not of psychosis. We found no evidence for the efficacy of monotherapy with an antidepressant or an antipsychotic. However, evidence suggests that the combination of an antidepressant plus an antipsychotic is more effective than antidepressant monotherapy (three RCTs; RR 1.49, 95% CI 1.12 to 1.98, P = 0.006), more effective than antipsychotic monotherapy (four RCTs; RR 1.83, 95% CI 1.40 to 2.38, P = 0.00001) and more effective than placebo (two identical RCTs; RR 1.86, 95% CI 1.23 to 2.82, P = 0.003). Risk of bias is considerable: there were differences between studies with regard to diagnosis, uncertainties around randomisation and allocation concealment, differences in treatment interventions (pharmacological differences between the various antidepressants and antipsychotics) and different outcome criteria. Psychotic depression is heavily understudied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone.

The aim of this review is to compare the efficacy of the various forms of drug treatment that have been used to treat psychotic depression. We did this by analysing all randomised controlled trials (RCTs) that investigated drug treatments for psychotic depression. We searched for these trials in a wide-ranging way. The search identified 3659 studies, but in the end, we found only 12 RCTs that met our inclusion criteria. These trials involved a total of 929 people. From these trials, we found evidence that the combination of an antidepressant plus an antipsychotic provides more effective treatment for psychotic depression than either treatment alone. However, our confidence in this conclusion is limited because the information came from only a small number of RCTs, which included small numbers of people. In addition, the types of people involved varied between RCTs, and the RCTs differed in design, which means that we cannot confidently generalise their findings.

10.1002/14651858.CD004044.pub4

cochrane-simplification-train-1079

cochrane-simplification-train-1079

One trial involving 1639 women was included. It compared SFH measurement with clinical abdominal palpation. There was no difference in the two reported primary outcomes of incidence of small-for-gestational age (risk ratio (RR) 1.32; 95% confidence interval (CI) 0.92 to 1.90, low quality evidence) or perinatal death.(RR 1.25, 95% CI 0.38 to 4.07; participants = 1639, low quality evidence). There were no data on the neonatal detection of large-for-gestational age (variously defined by authors). There was no difference in the reported secondary outcomes of neonatal hypoglycaemia, admission to neonatal nursery, admission to the neonatal nursery for IUGR (low quality evidence), induction of labour and caesarean section (very low quality evidence). The trial did not address the other outcomes specified in the 'Summary of findings' table (intrauterine death; neurodevelopmental outcome in childhood). GRADEpro software was used to assess the quality of evidence, downgrading of evidence was based on including a small single study with unclear risk of bias and a wide confidence interval crossing the line of no effect. There is insufficient evidence to determine whether SFH measurement is effective in detecting IUGR. We cannot therefore recommended any change of current practice. Further trials are needed.

We wanted to know which of these two methods is more likely to detect poor growth. Ultrasound assessment can also be used to detect growth restriction but this is costly and not always available, and there are concerns about its unnecessary use. We found only one randomised trial (involving 1639 women at 20 weeks’ gestation and above) comparing repeated measures of SFH with abdominal palpation. The trial found no difference between the two approaches in detecting poor growth. With such limited evidence, it is still not known whether one method is more effective than the other, and how these methods compare with ultrasound measurement. The main findings from this review were assessed for quality using software called GRADEpro. The overall evidence was of low/very low quality.

10.1002/14651858.CD008136.pub3

cochrane-simplification-train-1080

cochrane-simplification-train-1080

We included two RCTs examining a total of 191 young children, 180 of whom were included in the analyses. The two trials tested different comparisons. Both trials were at high risk of bias, particularly from lack of blinding of participants and personnel, and of outcome assessment. The trials did not record fingertip function, nail growth or nail deformity. The quality of the evidence for the reported outcomes was judged to be 'low' using the GRADE approach (i.e. further research is very likely to have an important impact on our confidence in the estimate of the effect and is likely to change the estimate). One trial compared a seven-day course of antibiotics with no antibiotics after formal surgical repair of fingertip entrapment injuries. One child in each group had an infection at day seven (1/66 antibiotic group versus 1/69 no antibiotic group; RR 1.05, 95% CI 0.07 to 16.37). Both participants with infections had a more severe injury (partial fingertip amputation). The other trial compared two different dressings (silicone net and paraffin gauze) for use after either surgical or initial conservative management of fingertip entrapment injuries. It reported that two of 20 children in the silicone group versus one of 25 in the paraffin group had complications of wound infection (RR 2.50, 95% CI 0.24 to 25.63) and that one of 20 children in the silicone group versus two of 25 in the paraffin group had skin necrosis (RR 0.63, 95% CI 0.06 to 6.41). All complications healed with conservative treatment. The results for mean healing times and mean number of dressing changes were similar between groups but benefits of either silicone or paraffin dressings could not be excluded (silicone mean 4.1 weeks versus paraffin mean 4.0 weeks; MD 0.10 weeks, 95% CI -0.61 to 0.81); (silicone mean 4.3 dressing changes versus paraffin mean 4.2 dressing changes; MD 0.10, 95% CI -0.57 to 0.77). The trial found that a silicone dressing was less likely to adhere to the wound or cause distress for the child at the one-week dressing change. There is a lack of evidence from RCTs to inform all key treatment decisions for the management of fingertip entrapment injuries in children. Given that the quality of evidence is low from one trial, we do not have conclusive evidence that prophylactic use of antibiotics after surgical repair fails to reduce risk of infection. The two children who experienced infection had more severe wounds. Similarly, the low quality evidence from one trial has not enabled us to draw firm conclusions regarding the effect on healing time or complications (infection, skin necrosis) at four-week follow-up between a silicone net dressing and a paraffin gauze dressing when applied post-surgery or after simple wound irrigation; however, the silicone net dressing may be easier to remove in the first week. Further RCTs are required in this area, preferably comparing surgical with conservative methods of managing fingertip entrapment injuries. Outcome assessment should include fingertip function, nail growth and nail deformity for a minimum of three months post treatment.

We searched the medical literature until 30 April 2013 for studies comparing different methods of treating fingertip entrapment injuries. Our review includes evidence from two studies where participants were randomly allocated to one of two conditions. The studies included 191 children with results available for a total of 180 children. Both the studies had weaknesses that could undermine the reliability of the results. Since the studies compared different methods, we could not combine their results. One study looked at the routine use of antibiotics in children with a surgically repaired fingertip injury to prevent infection. Due to the small number of children experiencing infection this study does not provide conclusive evidence of the effect of giving or withholding antibiotics. Only one child in each group had an infection after a week. Both children had had more severe injuries. The other study compared two different dressing types for use in fingertip entrapment injuries. The low number of complications was comparable in the two treatment groups. Due to the low number of participants in the study we could not be certain that length of time the injuries took to heal and the number of dressing changes were the same in the treatment groups. However, it also found that the dressing made of silicone caused less distress for the child when being changed after the first week, probably because it stuck less to the wound than the paraffin dressing. Overall, there is not enough evidence about how to best treat fingertip entrapment injuries in children. We recommend that further research is carried out, especially to see if surgery leads to better outcomes than simple wound cleaning and dressing. These studies should evaluate the effect of the treatment on fingertip function, nail growth and nail deformity for a minimum of three months after treatment.

10.1002/14651858.CD009808.pub2

cochrane-simplification-train-1081

cochrane-simplification-train-1081

Seven studies were included in the review, including a total of 298 children in the out-patient/home group. The one high quality trial identified suggested that home-based management of children with newly diagnosed type 1 diabetes may lead to slightly improved long term metabolic control (at two and three years follow-up). No differences between comparison groups were found in any of the psychosocial and behavioural variables assessed or in rates of acute diabetic complications within two years. Parental costs were found to be decreased, while health system costs were increased, leaving total social costs virtually unchanged. None of the other studies assessing metabolic control found a difference between the comparison groups. There seemed to be no differences in hospitalisations or acute diabetic complications between the out-patient/home groups and the hospital groups. Due to the generally low quality or limited applicability of the studies identified, the results of this review are inconclusive. On the whole, the data seem to suggest that where adequate out-patient/home management of type 1 diabetes in children at diagnosis can be provided, this does not lead to any disadvantages in terms of metabolic control, acute diabetic complications and hospitalisations, psychosocial variables and behaviour, or total costs.

This review asked the question whether there are any benefits or dangers of using this type of care. We found only data of limited quality and or applicability, so no clear answers are possible. The seven studies we looked at suggested that home management of children newly diagnosed with type 1 diabetes does not lead to any disadvantages in terms of blood glucose, acute diabetic complications and hospitalisations, psychological variables and behaviour, or total costs. This would be particularly relevant for children not acutely ill, but also for children who require a short period of initial treatment in the hospital.

10.1002/14651858.CD004099.pub2

cochrane-simplification-train-1082

cochrane-simplification-train-1082

Six trials including a total of 454 patients met our inclusion criteria. The methodological quality of most included trials was not high. It was shown that compared to placebo, Huperzine A had beneficial effects on the improvement of general cognitive function measured by MMSE (WMD 2.81; 95% CI 1.87 to 3.76; P < 0.00001) and ADAS-Cog at six weeks (WMD 1.91; 95% CI 1.27 to 2.55) and at 12 weeks (WMD 2.51; 95% CI 1.74 to 3.28), global clinical assessment measured by CDR (WMD -0.80; 95% CI -0.95 to -0.65) and CIBIC-plus (OR 4.32, 95% CI 2.37 to 7.90), behavioral disturbance measured by ADAS-non-Cog at six weeks (WMD -1.33, 95%CI -2.12 to -0.54) and at 12 weeks (WMD -1.52, 95% CI-2.39 to -0.65), and functional performance measured by ADL (WMD = -7.17; 95% CI -9.13 to -5.22; P < 0.00001). However, Huperzine A was not superior to placebo in the improvement of general cognitive function measured by Hasegawa Dementia Scale (HDS) (WMD: 2.78; 95% CI -0.17 to 5.73, P = 0.06) and specific cognitive function measured by Weshler Memory Scale (WMS) (WMD = 6.64; 95% CI -3.22 to 16.50; P = 0.19). No data were available on quality of life and caregiver burden. The adverse events of Huperzine A were mild and there were no significant differences of adverse events between Huperzine A groups and control groups. From the available evidence, Huperzine A seems to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance, with no obvious serious adverse events for patients with AD. However, only one study was of adequate quality and size. There is therefore inadequate evidence to make any recommendation about its use. Rigorous design, randomized, multi-centre, large-sample trials of Huperzine A for AD are needed to further assess the effects.

This review looked for randomized trials comparing Huperzine A with control in patients with AD. Six trials were identified but most trials were of low methodological quality. Although Huperzine A seemed to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance for patients with AD, the small trials with limited numbers of patients and the low methodological quality resulted in cautious assessment of the results. More large, high-quality randomized trials are needed.

10.1002/14651858.CD005592.pub2

cochrane-simplification-train-1083

cochrane-simplification-train-1083

We included only one study in this review, which compared two surgical interventions: pedicled buccal fat pad flap and buccal flap for the treatment of oro-antral communications. The study involved 20 participants. The risk of bias was unclear. The relevant outcome reported in this trial was successful (complete) closure of oro-antral communication. The quality of the evidence for the primary outcome was very low. The study did not find evidence of a difference between interventions for the successful (complete) closure of an oro-antral communication (RR 1.00, 95% Cl 0.83 to 1.20) one month after the surgery. All oro-antral communications in both groups were successfully closed so there were no adverse effects due to treatment failure. We did not find trials evaluating any other intervention for treating oro-antral communications or fistulae due to dental procedures. We found very low quality evidence from a single small study that compared pedicled buccal fat pad and buccal flap. The evidence was insufficient to judge whether there is a difference in the effectiveness of these interventions as all oro-antral communications in the study were successfully closed by one month after surgery. Large, well-conducted RCTs investigating different interventions for the treatment of oro-antral communications and fistulae caused by dental procedures are needed to inform clinical practice.

We searched various databases until 23 May 2018. Only one study, which was conducted in Iran, is included in our review. The study ran for two years and involved 20 people with OAC aged between 25 and 56 years. Participants were divided into two groups and two surgical treatments were compared for treating oro-antral communications; one group was treated with pedicled buccal fat pad flap (PBFPF) and the other with buccal flap (BF). The study did not find evidence of a difference between PBFPF and BF in terms of successful (complete) closure of OAC. Both interventions resulted in successful closure by one month after surgery. The study did not therefore report any adverse effects of treatment failure. It may not be possible to generalise these findings because the quality of the evidence was very low, due to unclear risk of bias and the small numbers studied in the single included trial. The evidence currently available is insufficient to draw reliable conclusions regarding the effects of interventions used to treat OAC or fistulae due to dental procedures. More well-designed and well-reported trials evaluating different interventions are needed to provide reliable evidence to inform clinical decisions.

10.1002/14651858.CD011784.pub3

cochrane-simplification-train-1084

cochrane-simplification-train-1084

We identified 15 trials, with a total of 3129 ICU participants from university-associated hospitals in the USA, Colombia, Saudi Arabia, Canada, Greece, Germany and Iran. There are two ongoing studies. Participants suffered from medical and surgical conditions, with a variety of inclusion criteria. Four studies used parenteral nutrition and nine studies used only enteral nutrition; it was unclear whether the remaining two used parenteral nutrition. Most of them could not achieve the proposed caloric targets, resulting in small differences in the administered calories between intervention and control groups. Most studies were funded by the US government or non-governmental associations, but three studies received funding from industry. Five studies did not specify their funding sources. The included studies suffered from important clinical and statistical heterogeneity. This heterogeneity did not allow us to report pooled estimates of the primary and secondary outcomes, so we have described them narratively. When comparing hypocaloric nutrition support with a control nutrition support, for hospital mortality (9 studies, 1775 participants), the risk ratios ranged from 0.23 to 5.54; for ICU mortality (4 studies, 1291 participants) the risk ratios ranged from 0.81 to 5.54, and for mortality at 30 days (7 studies, 2611 participants) the risk ratios ranged from 0.79 to 3.00. Most of these estimates included the null value. The quality of the evidence was very low due to unclear or high risk of bias, inconsistency and imprecision. Participants who received hypocaloric nutrition support compared to control nutrition support had a range of mean hospital lengths of stay of 15.70 days lower to 10.70 days higher (10 studies, 1677 participants), a range of mean ICU lengths of stay 11.00 days lower to 5.40 days higher (11 studies, 2942 participants) and a range of mean lengths of mechanical ventilation of 13.20 days lower to 8.36 days higher (12 studies, 3000 participants). The quality of the evidence for this outcome was very low due to unclear or high risk of bias in most studies, inconsistency and imprecision. The risk ratios for infectious complications (10 studies, 2804 participants) of each individual study ranged from 0.54 to 2.54. The quality of the evidence for this outcome was very low due to unclear or high risk of bias, inconsistency and imprecision We were not able to explain the causes of the observed heterogeneity using subgroup and sensitivity analyses or meta-regression. The included studies had substantial clinical heterogeneity. We found very low-quality evidence about the effects of prescribed hypocaloric nutrition support on mortality in hospital, in the ICU and at 30 days, as well as in length of hospital and ICU stay, infectious complications and the length of mechanical ventilation. For these outcomes there is uncertainty about the effects of prescribed hypocaloric nutrition, since the range of estimates includes both appreciable benefits and harms. Given these limitations, results must be interpreted with caution in the clinical field, considering the unclear balance of the risks and harms of this intervention. Future research addressing the clinical heterogeneity of participants and interventions, study limitations and sample size could clarify the effects of this intervention.

We included 15 trials with 3129 ICU surgical or medical participants from academic hospitals. Four studies used parenteral nutrition and nine studies used only enteral nutrition. The route was unclear in the remaining two studies. While the studies planned to give different amounts of calories in the experimental and control groups, the actual difference in calories was small. Most studies were funded by the US government or non-governmental associations, but three studies received funding from the industry. Five studies did not state how they were funded. The differences in the type of nutrition and type of participants across studies did not allow us to combine study results, so we describe the range of results across the individual studies. The number of deaths at the hospital, in the ICU and at 30 days in those who received low-calorie nutrition was similar to those in the control group. The length of hospital and ICU stay and the length of mechanical ventilation varied across studies, sometimes shorter and sometimes longer when compared to the control group. The number of infections also varied across studies. We tried to analyse subgroups of participants in order to clarify this variation, but the results were not consistent. The overall quality of evidence for each outcome according to GRADE classification varied from very low to low. This was due to problems in the design and conduct of the studies, the variation in the study results (inconsistency between studies) and the wide range of possible results (imprecision).

10.1002/14651858.CD007867.pub2

cochrane-simplification-train-1085

cochrane-simplification-train-1085

We included 121 trials. The risk of bias must be kept in mind as only 13 trials were double blind. Compared to placebo, misoprostol was associated with reduced failure to achieve vaginal delivery within 24 hours (average relative risk (RR) 0.51, 95% confidence interval (CI) 0.37 to 0.71). Uterine hyperstimulation, without fetal heart rate (FHR) changes, was increased (RR 3.52 95% CI 1.78 to 6.99). Compared with vaginal prostaglandin E2, intracervical prostaglandin E2 and oxytocin, vaginal misoprostol was associated with less epidural analgesia use, fewer failures to achieve vaginal delivery within 24 hours and more uterine hyperstimulation. Compared with vaginal or intracervical prostaglandin E2, oxytocin augmentation was less common with misoprostol and meconium-stained liquor more common. Lower doses of misoprostol compared to higher doses were associated with more need for oxytocin augmentation and less uterine hyperstimulation, with and without FHR changes. We found no information on women's views. Vaginal misoprostol in doses above 25 mcg four-hourly was more effective than conventional methods of labour induction, but with more uterine hyperstimulation. Lower doses (25 mcg four-hourly or less) were similar to conventional methods in effectiveness and risks. The authors request information on cases of uterine rupture known to readers. The vaginal route should not be researched further as another Cochrane review has shown that the oral route of administration is preferable to the vaginal route. Professional and governmental bodies should agree guidelines for the use of misoprostol, based on the best available evidence and local circumstances. [Note: The 27 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]

The review of 121 trials found that larger doses of misoprostol are more effective than prostaglandin and that oxytocin is used in addition less often. However, misoprostol also increases hyperstimulation of the uterus. With smaller doses, the results are similar to other methods. The trials reviewed are too small to determine whether the risk of rupture of the uterus is increased. More research is needed into the safety and best dosages of misoprostol. Another Cochrane review has shown that the oral route of administration is preferable to the vaginal route.

10.1002/14651858.CD000941.pub2

cochrane-simplification-train-1086

cochrane-simplification-train-1086

We included seven studies of 324 adults and children with eczema. Overall, the included studies had a high risk of bias. Four of the seven trials tested interventions with multiple components, and three tested a single intervention. Two of the seven trials included only children, four included children and adults, and one included only adults. Interventions to reduce or avoid exposure to house dust mite included covers for mattresses and bedding, increased or high-quality vacuuming of carpets and mattresses, and sprays that kill house dust mites. Four studies assessed our first primary outcome of 'Clinician-assessed eczema severity using a named scale'. Of these, one study (n = 20) did not show any significant short-term benefit from allergen impermeable polyurethane mattress encasings and acaricide spray versus allergen permeable cotton mattress encasings and placebo acaricide spray. One study (n = 60) found a modest statistically significant benefit in the Six Area, Six Sign Atopic Dermatitis (SASSAD) scale over six months (mean difference of 4.2 (95% confidence interval 1.7 to 6.7), P = 0.008) in favour of a mite impermeable bedding system combined with benzyltannate spray and high-filtration vacuuming versus mite permeable cotton encasings, water with a trace of alcohol spray, and a low-filtration vacuum cleaner. The third study (n = 41) did not compare the change in severity of eczema between the two treatment groups. The fourth study (n = 86) reported no evidence of a difference between the treatment groups. With regard to the secondary outcomes 'Participant- or caregiver-assessed global eczema severity score' and the 'Amount and frequency of topical treatment required', one study (n = 20) assessed these outcomes with similar results being reported for these outcomes in both groups. Four studies (n = 159) assessed 'Sensitivity to house dust mite allergen using a marker'; there was no clear evidence of a difference in sensitivity levels reported between treatments in any of the four trials. None of the seven included studies assessed our second primary outcome 'Participant- or caregiver-assessed eczema-related quality of life using a named instrument' or the secondary outcome of 'Adverse effects'. We were unable to combine any of our results because of variability in the interventions and paucity of data. We were unable to determine clear implications to inform clinical practice from the very low-quality evidence currently available. The modest treatment responses reported were in people with atopic eczema, specifically with sensitivity to one or more aeroallergens. Thus, their use in the eczema population as a whole is unknown. High-quality long-term trials of single, easy-to-administer house dust mite reduction or avoidance measures are worth pursuing.

We found seven randomised controlled trials, which included 324 adults and children with eczema. We conducted the search up to 14 August 2014. Two of the seven trials included only children; four included children and adults; and one only included adults. Four of the seven trials compared treatments made up of multiple different house dust mite reduction and avoidance measures, and three trials tested a single treatment. The treatments were compared against other house dust mite reduction or avoidance treatments, no treatment, a placebo intervention (e.g., cotton bed covers), or standard care only. We did not find any evidence to inform clinical practice. Some small treatment responses reported were in people with atopic eczema who were sensitive to one or more airborne allergens. We found no evidence of benefit in the other six included studies. Therefore, their use in the eczema population as a whole is unknown. High-quality longer trials of single, easy-to-use house dust mite reduction or avoidance measures should be performed. These seven very low-quality (Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach) small trials do not provide enough evidence to recommend any of the house dust mite reduction and avoidance measures tested.

10.1002/14651858.CD008426.pub2

cochrane-simplification-train-1087

cochrane-simplification-train-1087

We included 19 RCTs (1099 participants). The mean age of participants ranged from 47 to 66 years. Most studies (12/19) had fewer than 25 patients in each treatment group. Most studies (16/19) used immunonutrition formulas containing arginine, but there was variation in the actual products and amounts used, and in the length of intervention postoperatively. Follow-up time for outcome measurement varied considerably across studies, ranging from five days to greater than or equal to 16 months. Primary outcomes We found no evidence of a difference in the length of hospital stay (mean difference -2.5 days, 95% confidence interval (CI) -5.11 to 0.12; 10 studies, 757 participants; low-quality evidence). Similarly, we found no evidence of an effect of immunonutrition on wound infection (risk ratio (RR) 0.94, 95% CI 0.70 to 1.26; 12 studies, 812 participants; very low-quality evidence). Fistula formation may be reduced with immunonutrition; the absolute risks were 11.3% and 5.4% in the standard care and immunonutrition groups, with a RR of 0.48 (95% CI 0.27 to 0.85; 10 studies, 747 participants; low-quality evidence). We found no evidence of a difference in terms of tolerance of feeds ('adverse events') between treatments (RR 1.33, 95% CI 0.86 to 2.06; 9 studies, 719 participants; very low-quality evidence). Secondary outcomes We found no evidence of a difference between treatments in all-cause mortality (RR 1.33, 95% CI 0.48 to 3.66; 14 studies, 776 participants; low-quality evidence). Other postoperative complications such as pneumonia and urinary tract infections were not commonly reported. The risk of postoperative fistula formation may be reduced with immunonutrition, but we found no evidence of an effect of immunonutrition on any of the other outcomes that we assessed. The studies included in this review were generally small or at high risk of bias (or both). We judged the overall quality of the evidence to be low for the outcomes length of hospital stay and all-cause mortality, and very low for wound infection and adverse events. Further research should include larger, better quality studies.

We included 19 studies that recruited 1099 adults in total (studies ranged in size from 8 to 209 participants, but most (12 out of 19) had fewer than 25 participants per treatment group). The studies focused on people who were given immunonutrition or a standard feed before and after or only after their surgery. The studies varied in the length of time over which people were given the feeds, but this was usually at least five days. The evidence is current to February 2018. We did not find evidence of a difference in the length of hospital stay but there was wide variation between the individual studies in what they showed. We found some evidence that people who had immunonutrition may be about half as likely to have breakdown of their surgical wound called a fistula (a channel between the inside of the throat and the surface skin). We found no evidence that immunonutrition had any effect on wound infection (but not all studies were clear in how they measured this) or death. Study feeds were generally well tolerated and there was no evidence of a difference in adverse events such as diarrhoea between treatment groups. Other clinical complications such as pneumonia and urinary tract infections were not commonly reported, but there was little evidence of a reduction with immunonutrition. Most studies included in this review were small and poorly reported, which means that their results may be less reliable. More studies are needed that are larger, of better quality and conducted within current healthcare systems.

10.1002/14651858.CD010954.pub2

cochrane-simplification-train-1088

cochrane-simplification-train-1088

We included two trials (105 participants) comparing ergonomic versus placebo keyboards. Neither trial assessed the primary outcome (short-term overall improvement) or adverse effects of interventions. In one small trial (25 participants) an ergonomic keyboard significantly reduced pain after 12 weeks (MD -2.40; 95% CI -4.45 to -0.35) but not six weeks (MD -0.20; 95% CI -1.51 to 1.11). In this same study, there was no difference between ergonomic and standard keyboards in hand function at six or 12 weeks or palm-wrist sensory latency at 12 weeks. The second trial (80 participants) reported no significant difference in pain severity after six months when using either of the three ergonomic keyboards versus a standard keyboard. No trials comparing (i) ergonomic positioning or equipment with no treatment, (ii) ergonomic positioning or equipment with another non-surgical treatment, or (iii) different ergonomic positioning or equipment regimes, were found. There is insufficient evidence from randomised controlled trials to determine whether ergonomic positioning or equipment is beneficial or harmful for treating carpal tunnel syndrome.

This review aimed to find out how effective ergonomic treatments were in treating CTS. Only two studies were found (involving 105 participants). Both were designed to minimise research biases, but neither was of high quality. Neither study assessed short-term overall improvement, adverse effects or need for surgery as outcomes. One small study (25 participants) found an ergonomic keyboard reduced pain after 12 weeks but the second study reported no difference in pain severity between the keyboard groups at six months. Neither study found improvements in hand function or signs of CTS by people using ergonomic computer keyboards more than those experienced by people using standard keyboards. Based on the two studies in this review, which represent all the available evidence of sufficient quality for inclusion, there is no strong evidence for or against the use of ergonomic keyboards for the treatment of CTS.

10.1002/14651858.CD009600

cochrane-simplification-train-1089

cochrane-simplification-train-1089

We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancers Oral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5). The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6). Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT) Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3, although the uncertainty surrounding the effect estimate means that the 95% CI ranges from 2 NNTB, to 111 NNTH (number needed to treat in order to harm one additional person, i.e. for one additional person to develop oral mucositis). The results were similar for moderate to severe oral mucositis (RR 0.43, 95% CI 0.17 to 1.09, 5 studies, 270 analysed, low quality evidence). NNTB 3 (95% CI 2 NNTB to 17 NNTH). Severe oral mucositis is probably reduced (RR 0.38, 95% CI 0.20 to 0.72, 5 studies, 270 analysed, moderate quality evidence). Where 427 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 162 (95% CI 85 to 308), NNTB 4 (95% CI 3 to 9). Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance, and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies. There was limited or no evidence on the secondary outcomes of this review, or on patients undergoing other chemotherapies, radiotherapy, targeted therapy, or on comparisons of oral cryotherapy with other interventions or different oral cryotherapy regimens. Therefore no further robust conclusions can be made. There was also no evidence on the effects of oral cryotherapy in children undergoing cancer treatment. We are confident that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving 5FU for solid cancers. We are less confident in the ability of oral cryotherapy to reduce oral mucositis in adults receiving high-dose melphalan before HSCT. Evidence suggests that it does reduce oral mucositis in these adults, but we are less certain about the size of the reduction, which could be large or small. However, we are confident that there is an appreciable reduction in severe oral mucositis in these adults. This Cochrane review includes some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments.

Authors from the Cochrane Oral Health Group carried out this review of existing studies and the evidence is current up to 17 June 2015. It includes 14 studies published from 1991 to 2015 in which 1316 participants were randomised (1280 of whom were included in the analyses) to receive oral cryotherapy versus standard care (usually saline mouthrinses) or no treatment or a different treatment or a different method of oral cryotherapy, and the number of people developing oral mucositis of different severities was compared. Nearly all the evidence was on adults receiving oral cryotherapy versus standard care or no treatment. This evidence fell into two main groups: 1) adults receiving fluorouracil-based (5FU) treatment for solid cancers; or 2) adults receiving high-dose melphalan-based cancer treatment before haematopoietic stem cell transplantation (HSCT). HSCT is given to help the body to produce all types of blood cells, which are destroyed during cancer treatment. There is evidence showing that oral cryotherapy can lead to large reductions in the numbers of adults who get oral mucositis of all severities after receiving 5FU-based treatment for solid cancers. There is less certain evidence to suggest that oral cryotherapy may reduce the numbers of adults who get oral mucositis after receiving high-dose melphalan-based cancer treatment prior to HSCT. The evidence suggests that it does reduce oral mucositis in these adults, but the size of the reduction is much less certain. However, there is more certain evidence that there is a large reduction in severe oral mucositis in these adults. Oral cryotherapy did not cause any serious side effects in any of the participants of these studies, and most people seemed able to carry it out properly and complete it. The evidence presented, on the main outcome of whether or not people developed oral mucositis of all severities, is of moderate (because the nature of the oral cryotherapy treatment meant that the studies could not be 'blinded' which is a desirable characteristic of these studies) to low quality (because in addition to the above problem, the results of the individual studies were too different to give a precise result when they were combined).

10.1002/14651858.CD011552.pub2

cochrane-simplification-train-1090

cochrane-simplification-train-1090

We included nine RCTs (N = 2955 infertile couples). The quality of the evidence ranged from very low to low. The main limitations were high risk of bias in the included studies, imprecision, indirectness, and inconsistency. There were no data on cumulative live birth or ongoing pregnancy rate or cumulative clinical pregnancy rate. TLS with conventional morphological assessment of still TLS images versus conventional incubation and assessment It is unclear whether there is any difference between interventions in rates of live birth or ongoing pregnancy (odds ratio (OR) 0.91, 95% confidence interval (CI) 0.67 to 1.23, 3 RCTs, N = 826, I2 = 33%, low-quality evidence) or in miscarriage rates (OR 1.90, 95% CI 0.99 to 3.61, 3 RCTs, N = 826, I2 = 0%, low-quality evidence). The evidence suggests that if the rate of live birth or ongoing pregnancy associated with conventional incubation and assessment is 35%, the rate with the use of TLS with conventional morphological assessment of still TLS images would be between 27% and 40%, and if the miscarriage rate with conventional incubation is 4%, the rate associated with conventional morphological assessment of still TLS images would be between 4% and 14%. It is unclear whether there is a difference between the interventions in rates of stillbirth (OR 1.00, 95% CI 0.13 to 7.49, 1 RCT, N = 76, low-quality evidence) or clinical pregnancy (OR 1.06, 95% CI 0.79 to 1.41, 4 RCTs, N = 875, I2 = 0%, low-quality evidence). TLS utilising embryo selection software versus TLS with conventional morphological assessment of still TLS images All findings for this comparison were very uncertain due to the very low-quality of the evidence. No data were available on live birth, but one RCT reported ongoing pregnancy. It is unclear whether there is any difference between the interventions in rates of ongoing pregnancy (OR 0.61, 95% CI 0.32 to 1.20, 1 RCT, N = 163); miscarriage (OR 1.39, 95% CI 0.64 to 3.01, 2 RCTs, N = 463, I2 = 0%); or clinical pregnancy (OR 0.97, 95% CI 0.67 to 1.42, 2 RCTs, N = 463, I2 = 0%). The evidence suggests that if the rate of ongoing pregnancy associated with TLS with conventional morphological assessment of still TLS images is 47%, the rate associated with TLS utilising embryo selection software would be between 22% and 52%, and if the miscarriage rate associated with conventional morphological assessment of still TLS images is 5%, the rate associated with TLS utilising embryo selection software would be between 4% and 15%. No studies reported stillbirth. TLS utilising embryo selection software versus conventional incubation and assessment The findings for this comparison were also very uncertain due to the very low quality of the evidence. It is unclear whether there is any difference between the interventions in rates of live birth (OR 1.12, 95% CI 0.92 to 1.36, 3 RCTs, N = 1617, I2 = 84%). There was very low-quality evidence that TLS might reduce miscarriage rates (OR 0.63, 95% CI 0.45 to 0.89, 3 RCTs, N = 1617, I2 = 0%). It is unclear whether there is any difference between the interventions in rates of clinical pregnancy (OR 0.95, 95% CI 0.78 to 1.16, 3 RCTs, N = 1617, I2 = 89%). The evidence suggests that if the rate of live birth associated with conventional incubation and assessment is 48%, the rate with TLS utilising embryo selection software would be between 46% and 55%, and if the miscarriage rate with conventional incubation and assessment is 11%, the rate associated with TLS would be between 5% and 10%. No stillbirths occurred in the only study reporting this outcome. There is insufficient good-quality evidence of differences in live birth or ongoing pregnancy, miscarriage and stillbirth, or clinical pregnancy to choose between TLS, with or without embryo selection software, and conventional incubation. As the evidence is of low or very low-quality, our findings should be interpreted with caution.

The evidence is current to January 2019. We included nine studies (randomised controlled trials, that is studies in which participants are assigned to one of two or more treatment groups using a random method) of 2955 infertile couples undergoing IVF or ICSI. There were three different study designs: (1) TLS with conventional assessment of still TLS images versus conventional incubation and assessment; (2) TLS utilising embryo selection software versus TLS with conventional assessment of still TLS images; and (3) TLS utilising embryo selection software versus conventional incubation and assessment. TLS with conventional assessment of still TLS images versus conventional incubation and assessment All the evidence for this comparison was low-quality. It is unclear whether there is any difference between the interventions in rates of livebirth or ongoing pregnancy or miscarriage. The evidence suggests that if the rate of livebirth or ongoing pregnancy associated with conventional incubation and assessment is 35%, the rate with use of TLS with conventional morphological assessment of still TLS images would be between 27% and 40%, and if the miscarriage rate with conventional incubation is 4%, the rate associated with conventional morphological assessment of still TLS images would be between 4% and 14%. It is unclear whether there is a difference between interventions in rates of stillbirth or clinical pregnancy. TLS utilising embryo selection software versus TLS with conventional assessment of still TLS images All findings for this comparison were very uncertain due to very low-quality evidence. No data were available on livebirth, but one study reported ongoing pregnancy. It is unclear whether there is any difference between interventions in rates of ongoing pregnancy, miscarriage, or clinical pregnancy. The evidence suggests that if the rate of ongoing pregnancy associated with TLS with conventional morphological assessment of still TLS images is 47%, the rate associated with TLS utilising embryo selection software would be between 22% and 52%, and if the miscarriage rate associated with conventional morphological assessment of still TLS images is 5%, the rate associated with TLS utilising embryo selection software would be between 4% and 15%. No studies reported stillbirth. TLS utilising embryo selection software versus conventional incubation and assessment All findings for this comparison were very uncertain due to the very low-quality of the evidence. It is unclear whether there is any difference between interventions with respect to rates of livebirth or clinical pregnancy. The evidence suggests lower rates of miscarriage in the TLS group for the outcome of miscarriage. The evidence suggests that if the livebirth rate associated with conventional incubation is 48%, the rate with the use of TLS would be between 46% and 55%, and if the miscarriage rate with conventional incubation is 11%, the rate associated with TLS would be between 5% and 10%. There is no good evidence showing that TLS is more or less effective than conventional methods of embryo incubation. Patients may wish to take part in randomised controlled trials on TLS in order to add to the existing evidence base and to help guide assisted reproductive technology patients in the future. The quality of the evidence ranged from very low to low. The main limitations were high risk of bias in the included studies, imprecision, indirectness, and inconsistency.

10.1002/14651858.CD011320.pub4

cochrane-simplification-train-1091

cochrane-simplification-train-1091

Data from 8447 participants in 23 studies were included in the analyses. In people undergoing surgery for closed fracture fixation, single dose antibiotic prophylaxis significantly reduced deep surgical site infection (risk ratio 0.40, 95% CI 0.24 to 0.67), superficial surgical site infections, urinary infections, and respiratory tract infections. Multiple dose prophylaxis had an effect of similar size on deep surgical site infection (risk ratio 0.35, 95% CI 0.19 to 0.62), but significant effects on urinary and respiratory infections were not confirmed. Although the risk of bias in many studies as reported was unclear, sensitivity analysis showed that removal from the meta-analyses of studies at high risk of bias did not alter the conclusions. Economic modelling using data from one large trial indicated that single dose prophylaxis with ceftriaxone is a cost-effective intervention. Data for the incidence of adverse effects were very limited, but as expected they appeared to be more common in those receiving antibiotics, compared with placebo or no prophylaxis. Antibiotic prophylaxis should be offered to those undergoing surgery for closed fracture fixation.

This review included 23 trials, involving a total of 8447 participants. The review found that antibiotics are effective in reducing the incidence of infection, both at the surgical-wound site and in the chest and urinary tract. The effect of a single dose of antibiotic is similar to that from multiple doses if the antibiotic chosen is active through the period from the beginning of surgery until the wound is sealed. There were too few data available to confirm the expected tendency for increased adverse drug-related events such as gut problems and skin reactions.

10.1002/14651858.CD000244.pub2

cochrane-simplification-train-1092

cochrane-simplification-train-1092

From 6394 references, we included four studies evaluating 77 participants, including two RCTs, studying children and adults with hypoglycaemia, respectively, and two non-RCTs with healthy volunteers. The studies included three different routes of glucose administration (sublingual, buccal and a combination of oral and buccal administration). All studies had a high risk of bias in one or more 'Risk of bias' domain. Glucose administration by the sublingual route, in the form of table sugar under the tongue, resulted in a higher blood glucose concentration after 20 minutes compared with the oral route in the very specific setting of children with hypoglycaemia and symptoms of concomitant malaria or respiratory tract infection (MD 17 mg/dL, 95% CI 4.4 to 29.6; P = 0.008; 1 study; 42 participants; very low-quality evidence). Resolution of hypoglycaemia at 80 minutes may favour sublingual administration (RR 2.10, 95% CI 1.24 to 3.54; P = 0.006; 1 study; 42 participants; very low-certainty evidence), but no substantial difference could be demonstrated at 20 minutes (RR 1.26, 95% CI 0.91 to 1.74; P = 0.16; 1 study; 42 participants; very low-certainty evidence). A decrease in the time to resolution of hypoglycaemia was found in favour of sublingual administration (MD -51.5 min, 95% CI -58 to -45; P < 0.001; 1 study; 42 participants; very low-certainty evidence). No adverse events were reported in either group. No data were available for resolution of symptoms and time to resolution of symptoms, and treatment delay. Glucose administered by the buccal route in one study resulted in a lower plasma glucose concentration after 20 minutes compared with oral administration (MD -14.4 mg/dL, 95% CI -17.5 to -11.4 for an imputed within-participants correlation coefficient of 0.9; P < 0.001; 1 trial; 16 participants; very low-quality evidence). In another study there were fewer participants with increased blood glucose at 20 minutes favouring oral glucose (RR 0.07, 95% CI 0.00 to 0.98; P = 0.05; 1 study; 7 participants; very low-certainty evidence). No data were available for resolution of symptoms and time to resolution of symptoms, resolution of hypoglycaemia and time to resolution of hypoglycaemia, adverse events, and treatment delay. For the combined oral and buccal mucosal route (in the form of a dextrose gel) the MD was -15.3 mg/dL, 95%CI -33.6 to 3; P = 0.09; 1 study; 18 participants; very low-quality evidence . No improvement was identified for either route in the resolution of symptoms at 20 minutes or less following glucose administration (RR 0.36, 95% CI 0.12 to 1.14; P = 0.08; 1 study; 18 participants; very low-certainty evidence). No data were available for time to resolution of symptoms, resolution of hypoglycaemia and time to resolution of hypoglycaemia, adverse events, and treatment delay. When providing first aid to individuals with hypoglycaemia, oral glucose administration results in a higher blood glucose concentrations after 20 minutes when compared with buccal administration of glucose. A difference in plasma glucose concentration could not be demonstrated, when administering a dextrose gel, defined as “a combined oral and buccal mucosal route” compared to oral administration of a glucose tablet or solution. In the specific population of children with concomitant malaria and respiratory illness, sublingual sugar results in a higher blood glucose concentration after 20 minutes when compared with oral administration.These results need to be interpreted cautiously because our confidence in the body of evidence is very low due to the low number of participants and studies as well as methodological deficiencies in the included studies.

We identified four studies. One randomised study (clinical trials where people are randomly allocated to one of two or more treatment groups) compared sublingual glucose administration, in the form of table sugar, with an oral administration in 42 hypoglycaemic children between one and 15 years old. Two non-randomised studies compared buccal glucose administration with oral administration in 23 adult healthy fasting volunteers. One randomised study compared a dextrose gel with oral administration of glucose in 18 people with type 1 diabetes and hypoglycaemia. Providing sugar under the tongue (sublingual) resulted in a greater rise in blood glucose after 20 minutes than giving the sugar orally, but this was in a specific setting including children with hypoglycaemia and symptoms of concomitant malaria or respiratory tract infection. On the other hand, giving glucose by the buccal mucosa route resulted in a lower plasma glucose concentration than with the oral route. For dextrose gel (where uptake of the glucose occurs through a combination of oral swallowing and via the buccal mucosa), no clear benefit was shown compared to oral glucose administration (glucose tablets or glucose solutions). Most studies did not report on time to resolution of symptoms, resolution of hypoglycaemia as defined by blood glucose levels above a certain threshold, time to resolution of hypoglycaemia, adverse events, and treatment delay. The evidence is of very low certainty due to limitations in study design, few studies and small number of participants in the studies, and because half of the studies were performed with healthy volunteers rather than in people with characteristic hypoglycaemia.

10.1002/14651858.CD013283.pub2

cochrane-simplification-train-1093

cochrane-simplification-train-1093

A total of three studies met the inclusion criteria, allocating 2971 participants to the intervention and control groups. The total number of participants randomised to the intervention groups was 1467, whilst 1504 were randomised to the control groups. The length of intervention was 9, 12 and 24 months in the different trials. The use of TTM SOC in combination with diet or physical activity, or both, and other interventions in the included studies produced inconclusive evidence that TTM SOC interventions led to sustained weight loss (the mean difference between intervention and control groups varied from 2.1 kg to 0.2 kg at 24 months; 2971 participants; 3 trials; low quality evidence). Following application of TTM SOC there were improvements in physical activity and dietary habits, such as increased exercise duration and frequency, reduced dietary fat intake and increased fruit and vegetable consumption (very low quality evidence). Weight gain was reported as an adverse event in one of the included trials. None of the trials reported health-related quality of life, morbidity, or economic costs as outcomes. The small number of studies and their variable methodological quality limit the applicability of the findings to clinical practice. The main limitations include inadequate reporting of outcomes and the methods for allocation, randomisation and blinding; extensive use of self-reported measures to estimate the effects of interventions on a number of outcomes, including weight loss, dietary consumption and physical activity levels; and insufficient assessment of sustainability due to lack of post-intervention assessments. The evidence to support the use of TTM SOC in weight loss interventions is limited by risk of bias and imprecision, not allowing firm conclusions to be drawn. When combined with diet or physical activity, or both, and other interventions we found very low quality evidence that it might lead to better dietary and physical activity habits. This systematic review highlights the need for well-designed RCTs that apply the principles of the TTM SOC appropriately to produce conclusive evidence about the effect of TTM SOC lifestyle interventions on weight loss and other health outcomes.

We included three studies in our systematic review. Altogether the studies evaluated 2971 participants, with 1467 participants allocated to the intervention groups and 1504 to the control groups. The studies had a length of intervention of 9, 12 and 24 months. This plain language summary was current as of December 2013. The use of the TTM SOC in combination with diet or physical activity, or both, and other interventions in the included studies provided inconclusive evidence about the impact of such interventions on sustainable weight loss (mean difference in favour of the TTM SOC was between 2.1 kg and 0.2 kg at 24 months). However, other positive effects were noted, such as changes in physical activity and dietary habits that included increased exercise duration and frequency, reduced fat intake and increased fruit and vegetable consumption. The studies did not report other important outcomes such as health-related quality of life, illness (morbidity) and economic costs. Overall, the quality of the evidence was low or very low. The main limitations included incomplete reporting of outcomes, methodological shortcomings, extensive use of self-reported measures and insufficient assessment of sustainability due to the lack of long-term assessments.

10.1002/14651858.CD008066.pub3

cochrane-simplification-train-1094

cochrane-simplification-train-1094

No study examined the effect of screening (clinical and/or ultrasound) and early treatment versus not screening and later treatment. One study reported universal ultrasound compared to clinical examination alone did not result in a significant reduction in late diagnosed DDH or surgery but was associated with a significant increase in treatment. One study reported targeted ultrasound compared to clinical examination alone did not result in a significant reduction in late diagnosed DDH or surgery, with no significant difference in rate of treatment. Meta-analysis of two studies found universal ultrasound compared to targeted ultrasound did not result in a significant reduction in late diagnosed DDH or surgery. There was heterogeneity between studies reporting the effect on treatment rate. Meta-analysis of two studies found delayed ultrasound and targeted splinting compared to immediate splinting of infants with unstable (but not dislocated) hips resulted in no significant difference in the rate of late diagnosed DDH. Both studies reported a significant reduction in treatment with use of delayed ultrasound and targeted splinting. One study reported delayed ultrasound and targeted splinting compared to immediate splinting of infants with mild hip dysplasia on ultrasound resulted in no significant difference in late diagnosed DDH but a significant reduction in treatment. No infants in either group received surgery. There is insufficient evidence to give clear recommendations for practice. There is inconsistent evidence that universal ultrasound results in a significant increase in treatment compared to the use of targeted ultrasound or clinical examination alone. Neither of the ultrasound strategies have been demonstrated to improve clinical outcomes including late diagnosed DDH and surgery. The studies are substantially underpowered to detect significant differences in the uncommon event of late detected DDH or surgery. For infants with unstable hips or mildly dysplastic hips, use of delayed ultrasound and targeted splinting reduces treatment without significantly increasing the rate of late diagnosed DDH or surgery.

This review found no studies that compared the benefits and costs of early screening versus not screening for hip problems. Studies that compared the addition of ultrasound to clinical examination reported that when ultrasound was performed on all infants, the rate of treatment increased with no significant difference in rate of late detected dysplasia or surgery. Targeted ultrasound to infants at high risk of hip dysplasia did not significantly increase the rate of treatment but also did not significantly reduce the rate of late detected dysplasia or surgery. It is not possible to give clear recommendations for hip screening of newborn infants from the available evidence. Where infants are clinically detected as having unstable but not dislocated hips, or are detected on ultrasound to have mild hip dysplasia, there is evidence that delaying treatment by two to eight weeks reduces the need for treatment without a significant increase in late diagnosed dysplasia or surgery.

10.1002/14651858.CD004595.pub2

cochrane-simplification-train-1095

cochrane-simplification-train-1095

Seven studies were included in the analysis (368 participants in total). All were on mania, hypomania, mixed episodes or rapid-cycling disorder. Overall, their methodological quality was relatively low. There was no difference in the primary outcome analysis – a fall of  50% or more on the Young Mania Rating Scale (YMRS) - between oxcarbazepine and placebo (N=1, n=110, OR =2.10, 95% CI 0.94 to 4.73) in one study, conducted in children; no studies were available in adult participants. In comparison with other mood stabilisers, there was no difference between oxcarbazepine and valproate as an antimanic agent using the primary outcome (50% or more fall in YMRS, OR=0.44, 95% CI 0.10 to 1.97, 1 study, n=60, P=0.273) or the secondary outcome measure (differences in YMRS between the two groups, SMD=0.18, 95% CI -0.24 to 0.59, 2 studies, n=90, P=0.40). No primary or secondary efficacy outcome measures were found comparing oxcarbazepine with lithium monotherapy. As an adjunctive treatment to lithium, oxcarbazepine reduced depression rating scale scores more than carbamazepine in a group of manic participants on the Montgomery-Åsberg Depression Rating Scale (MADRS) (SMD=- 1.12, 95% CI -1.71 to -0.53, 1 study, n=52, P=0.0002) and on the Hamilton Depression Rating Scale (HDRS) (SMD=- 0.77, 95% CI -1.35 to -0.20, 1 study, n=52, P=0.008). There was a higher incidence of adverse effects, particularly neuropsychiatric, in participants randomised to oxcarbazepine compared to those on placebo (1 study, n=115, 17% to 39% of participants on oxcarbazepine had at least one such event compared to 7% to 10% on placebo).There was no difference in adverse events rates between oxcarbazepine and other mood stabilisers or haloperidol. Currently, there are insufficient trials of adequate methodological quality on oxcarbazepine in the acute treatment of bipolar disorder to inform us on its efficacy and acceptability. Studies predominantly examine the treatment of mania: there are data from subgroup analysis on mixed affective, hypomania and rapid-cycling states. From the few studies included in this review, oxcarbazepine did not differ in efficacy compared to placebo in children and adolescents. It did not differ from other active agents in adults. It may have a poorer tolerability profile compared to placebo. No data were found on outcomes relevant to patients and clinicians, such as length of hospital admission. There is a need for adequately powered randomised controlled trials of good methodological quality to inform us of the therapeutic potential of oxcarbazepine across the spectrum of acute episodes in bipolar disorder.

In this review we found seven studies that were eligible for inclusion, of which four studies compared the efficacy of oxcarbazepine to placebo or to other medications used in treating mania. While there was no evidence that oxcarbazepine worked better compared to a placebo, it did have similar efficacy to more accepted medications for the treatment of the illness. Two studies examined its acceptability to participants. Oxcarbazepine may cause more side effects than placebo. No differences in side effects were found between oxcarbazepine and other active medications. All the studies examined mania, hypomania, mixed episodes or rapid-cycling disorder. More studies of better methodological quality are needed if we are to be certain whether oxcarbazepine works or not when treating mania, mixed episodes, depression and rapid-cycling in bipolar disorder.

10.1002/14651858.CD004857.pub2

cochrane-simplification-train-1096

cochrane-simplification-train-1096

We identified 2190 unique records, evaluated the full text of seven studies and included one study with 1236 participants. This study reported tumour recurrence in 2.3% of women in the oestrogen arm versus 1.9% of women receiving placebo (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.54 to 2.50; very low-certainty evidence). The study reported one woman in the HRT arm (0.16%) and three women in the placebo arm (0.49%) who developed breast cancer (new malignancy) during follow-up (RR 0.80, 95% CI 0.32 to 2.01; 1236 participants, 1 study; very low-certainty evidence). The study did not report on symptom relief, overall survival or progression-free survival for HRT versus placebo. However, they did report the percentage of women alive with no evidence of disease (94.3% in the HRT group and 95.6% in the placebo group) and the percentage of women alive irrespective of disease progression (95.8% in the HRT group and 96.9% in the placebo group) at the end of the 36 months' follow-up. The study did not report time to recurrence and it was underpowered due to closing early. The authors closed it as a result of the publication of the Women's Health Initiative (WHI) study, which, at that time, suggested that risks of exogenous hormone therapy outweighed benefits and had an impact on study recruitment. No assessment of efficacy was reported. Currently, there is insufficient high-quality evidence to inform women considering HRT after treatment for endometrial cancer. The available evidence (both the single RCT and non-randomised evidence) does not suggest significant harm, if HRT is used after surgical treatment for early-stage endometrial cancer. There is no information available regarding use of HRT in higher-stage endometrial cancer (FIGO stage II and above). The use of HRT after endometrial cancer treatment should be individualised, taking account of the woman's symptoms and preferences, and the uncertainty of evidence for and against HRT use.

We searched clinical trial databases to look for any evidence of effectiveness and safety of HRT use in women who had had endometrial cancer up to May 2017. We only found one study that randomly allocated women to receive either HRT or a placebo (pretend treatment). This found no difference in the likelihood of the cancer regrowth between the two groups. They showed that HRT may or may not increase the risk of recurrence of developing a new cancer. They did not provide any information on survival or symptom relief. However, the study was not completed due to poor recruitment into the clinical trial, so was not large enough to definitively say whether the use of HRT could be recommended after treatment for early endometrial cancer. We are uncertain whether HRT increases the risk of recurrence after a diagnosis of endometrial cancer, as the certainty of the current evidence was very low. We identified only one randomised trial and this trial did not include enough women to definitely answer the question. This trial also had areas of potential bias that reduced our certainty in the results. Limited, very-low certainty, evidence suggests that HRT may have little or no effect on the risk of endometrial cancer returning for women who have been treated surgically for an early-stage endometrial cancer. There were no data to say whether HRT had an effect on overall survival after hysterectomy for endometrial cancer.

10.1002/14651858.CD008830.pub3

cochrane-simplification-train-1097

cochrane-simplification-train-1097

For this update, we added five studies (606 participants), meaning that the review now includes a total of 12 RCTs involving 2171 participants with COPD. Average age of participants was 66 years, male participants accounted for 67% and mean forced expiratory volume in one second (FEV1) was 1.2 L (five studies), 54% predicted (four studies). We assessed risks of selection, attrition and reporting bias as low, and risks of performance and detection bias as moderate. Compared with control, the vaccine group had a lower likelihood of developing community-acquired pneumonia (CAP) (odds ratio (OR) 0.59 , 95% confidence interval (CI) 0.41 to 0.85; six studies, n = 1372; GRADE: moderate), but findings did not differ specifically for pneumococcal pneumonia (Peto OR 0.26, 95% CI 0.05 to 1.31; three studies, n = 1158; GRADE: low). The number needed to treat for an additional beneficial outcome (NNTB) (preventing one episode of CAP) was 19 (95% CI 13 to 52). Mortality from cardiorespiratory causes did not differ between vaccine and control groups (OR 1.07, 95% CI 0.69 to 1.66; three studies, n = 888; GRADE: moderate), nor did all-cause mortality differ (OR 1.00, 95% CI 0.72 to 1.40; five studies, n = 1053; GRADE: moderate). The likelihood of hospital admission for any cause, or for cardiorespiratory causes, did not differ between vaccine and control groups. Vaccination significantly reduced the likelihood of a COPD exacerbation (OR 0.60, 95% CI 0.39 to 0.93; four studies, n = 446; GRADE: moderate). The NNTB to prevent a patient from experiencing an acute exacerbation was 8 (95% CI 5 to 58). Only one study (n = 181) compared the efficacy of different vaccine types - 23-valent PPV versus 7-valent PCV - and reported no differences for CAP, all-cause mortality, hospital admission or likelihood of a COPD exacerbation, but investigators described a greater likelihood of some mild adverse effects of vaccination with PPV-23. Injectable polyvalent pneumococcal vaccination provides significant protection against community-acquired pneumonia, although no evidence indicates that vaccination reduced the risk of confirmed pneumococcal pneumonia, which was a relatively rare event. Vaccination reduced the likelihood of a COPD exacerbation, and moderate-quality evidence suggests the benefits of pneumococcal vaccination in people with COPD. Evidence was insufficient for comparison of different pneumococcal vaccine types.

For this updated review, we identified five new studies (606 participants), bringing the total number of studies to 12, involving 2171 participants with COPD. The average age of participants was 66 years, 67% were male and participants had received a diagnosis of moderate to severe COPD. Eleven studies compared an injectable vaccine versus a control, and one study compared two different types of injectable vaccine. Key results People who were vaccinated were less likely to experience an episode of community-acquired pneumonia; 19 people with COPD (95% confidence interval (CI) 13 to 52) would have to be vaccinated to prevent one episode of pneumonia. Vaccination made no difference in the risk of pneumococcal pneumonia due to S pneumoniae or in the chance of dying or of being admitted to hospital. People who were vaccinated were less likely to experience a COPD exacerbation; eight people with COPD (95% CI 5 to 58) would have to be vaccinated to prevent one person from having an acute exacerbation. We found no difference in effectiveness between the two types of injectable vaccine. Quality of the evidence Evidence in this review is generally independent and reliable, and we are moderately certain about the results. Conclusions In line with current guidance, this review suggests that all people with COPD should be given pneumococcal vaccination to provide some protection against community-acquired pneumonia, and to reduce the chance of an acute exacerbation.

10.1002/14651858.CD001390.pub4

cochrane-simplification-train-1098

cochrane-simplification-train-1098

While there were no eligible trials in people with VWD identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of EACA published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference (RD) of -0.64 (95% confidence interval (CI) -0.93 to - 0.36) and the EACA trial a RD of -0.50 (95% CI 0.77 to -0.22). The combined RD of both trials was -0.57 (95% CI -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping EACA (combined RD of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the EACA trial, but overall the risk of bias appeared to be low for both trials. Despite the discovery of a beneficial effect of systemically administered tranexamic acid and EACA in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with VWD.

In the epsilon aminocaproic acid trial, the trial physicians assigned each person to receive a placebo or the active treatment based on a pair-matching technique for age, factor-assay and the number of extractions. The fact that the trial physicians made this decision may have introduced a selection bias. However, we do not think that this had a major impact on the trial's conclusions. Overall, the two trials were small and differed from each other in terms of how many of the people taking part had severe haemophilia, the simultaneous use of clotting factor concentrates and the different antifibrinolytic treatment schedules. We rated the overall quality of the evidence as low for using antifibrinolytic medicine to prevent bleeding in people with haemophilia after minor oral surgery or dental extractions. No evidence was found for people with Von Willebrand disease. It could however be argued that, if antifibrinolytic medicine works for people with haemophilia, it is likely that the medicine will also work for people with other bleeding disorders undergoing dental extractions or minor oral surgery.

10.1002/14651858.CD011385.pub3

cochrane-simplification-train-1099

cochrane-simplification-train-1099

We included five single-centre trials (undertaken in Italy) with 153 women and 154 pregnancies in this review. There were no clear differences in the primary outcomes reported between CSII and MDI in the included trials: caesarean section (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.66 to 1.77; three trials, 71 women, evidence graded very low), large-for-gestational age (RR 4.15, 95% CI 0.49 to 34.95; three trials, 73 infants; evidence graded very low), and perinatal mortality (RR 2.33, 95% CI 0.38 to 14.32; four trials, 83 infants, evidence graded very low). Other primary outcomes were not reported in these trials (hypertensive disorders of pregnancy, development of type 2 diabetes, composite outcome of serious neonatal outcomes, and neurosensory disability). There was no clear evidence of differences in the maternal secondary outcomes: maternal weight gain during pregnancy, 24 hour mean blood glucose in each trimester, mean maternal HbA1c in each trimester, maternal hypoglycaemia, and maternal hyperglycaemia. The included studies did not report several GRADE outcomes: perineal trauma, return to pre-pregnancy weight, postnatal depression, induction of labour. Many maternal secondary outcomes were also not reported. In two trials, including a total of 61 infants, CSII was associated with an increase in mean birthweight compared with MDI (mean difference (MD) 220.56 g, 95% CI -2.09 g to 443.20 g; P = 0.05). However, the large CI including anything from a small reduction to an increase in mean birthweight and the lack of a difference in macrosomia rate (RR 3.20, CI 0.14 to 72.62; two trials, 61 infants) suggests uncertainty. Large-for-gestational age (see above), andsmall-for-gestational age also suggests uncertainty of effect. No significant differences were found in: gestation at delivery, preterm birth < 37 weeks' gestation, preterm birth < 32 weeks' gestation, neonatal hypoglycaemia (evidence graded very low),respiratory distress syndrome, neonatal hyperbilirubinaemia, and fetal anomaly. There were no data reported on many important infant outcomes, including the GRADE outcomes adiposity and diabetes. There was no follow-up of infants in childhood or adulthood, so longer-term outcomes were not reported. The only outcome reported for use of health service resources wasmaternal days hospitalised, which did not show a difference between groups in the small number of women included (MD 9.40, CI -6.04 to 24.84; one trial, 10 women). The methods used by the trials were poorly reported, for example although blinding of participants and clinicians regarding intervention allocation is impossible, it is possible to blind assessors and this along with other aspects of trial methods was not reported, which means that the trials are at an unclear or high risk of bias. We do not know if the women who participated were representative, and therefore if the results can be generalised. Most GRADE outcomes were not reported. For the GRADE outcomes that were reported, our assessment was that the evidence is very low quality (caesarean section, large-for-gestational age, perinatal mortality, andneonatal hypoglycaemia). This was due to design limitations in the included trials, small sample sizes in the trials contributing data, wide CIs crossing both the line of no effect and the line of appreciable benefit and/or harm, and often few events. We are therefore uncertain whether CSII or MDI improves outcomes for pregnant women with diabetes and their infants, and the results of further studies may differ substantially from those presented in this review. There is no evidence to support the use of one particular form of insulin administration over another for pregnant women with diabetes. There are only a small number of trials appropriate for meta-analysis, a small number of women included and questionable generalisability of the trial population. Pump technology has progressed since these trials were undertaken. Well-designed randomised trials are required to evaluate comparisons such as patch pumps against MDI and more conventional CSII against MDI. These trials should be adequately powered to assess the effect of interventions, and report the core set of outcomes used in Cochrane reviews of diabetes in pregnancy. Trials to assess the effects of pumps on birthweight and macrosomia rates are needed. It would be beneficial for future trials to undertake longer-term follow-up of participants and their infants, assess women's preferences, and conduct an economic evaluation.

Five randomised trials involving 153 women (154 pregnancies) were included. These trials did not report many of the outcomes we had hoped to look at. The evidence was judged to be very low quality for important outcomes (caesarean section, large-for-gestational age, perinatal mortality, and neonatal hypoglycaemia). This was because the trials were small, may not have been fair tests, and did not show a clear difference between MDI and CSII. There were no clear differences in any of the reported outcomes between women who had insulin via a pump rather than as multiple injections. For mothers, this included caesarean section, weight gain during pregnancy, and blood sugar levels. For babies, this included the baby's weight, if they were born premature, and problems such as difficulty breathing, a low Apgar score at birth, low blood sugar, jaundice, or physical abnormalities. In one small trial, there was no difference in the number of days mothers spent in hospital. This was the only measure of cost or use of health service resources reported. The trials did not provide enough information to know whether an insulin pump or multiple injections are better for a pregnant woman with diabetes or her baby. More research is needed, with bigger groups of women, good reporting of how the trials were undertaken, more outcomes assessed and reported, and using the latest pump technology and insulins.

10.1002/14651858.CD005542.pub3