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cochrane-simplification-train-3500

cochrane-simplification-train-3500

Three trials, which included 140 infants, met the inclusion criteria. All three trials compared a nebulized dose of salbutamol with placebo; in one of the three trials newborns were assigned to two different doses of the intervention. We found differences in the duration of oxygen therapy (mean difference (MD) -43.10 hours, 95% confidence interval (CI) -81.60 to -4.60). There were no differences in the need for continuous positive airway pressure (risk ratio (RR) 0.73, 95% CI 0.38 to 1.39; risk difference (RD) -0.15, 95% CI -0.45 to 0.16; 1 study, 46 infants) or the need for mechanical ventilation (RR 1.50, 95% CI 0.06 to 34.79; RD 0.03, 95% CI -0.08 to 0.14; 1 study, 46 infants). Tests for heterogeneity were not applicable for any of the analyses as only one study was included. Among secondary outcomes, we found no differences in terms of duration of hospital stay and tachypnea. The quality of the evidence was very low due to the imprecision of the estimates. One trial is ongoing. At present there is insufficient evidence to determine the efficacy and safety of salbutamol in the management of transient tachypnea of the newborn. The quality of evidence was low due to paucity of included trials, small sample sizes and overall poor methodologic quality.

In medical literature searches complete to March 2016, we identified and included three clinical trials with 140 newborns comparing salbutamol with placebo. Two studies evaluated a single, nebulized (where the medicine is given in a fine mist) dose of salbutamol, and one study evaluated two different dosages. We found one additional trial that is still underway. Salbutamol reduced the duration of treatment with oxygen in newborns with transient tachypnea (reported in one study); whereas it did not affect the need for respiratory support or any other relevant outcomes. The results of this systematic review were consistent with either a benefit or a detrimental effect of salbutamol and did not provide a definitive answer to the review question.

10.1002/14651858.CD011878.pub2

cochrane-simplification-train-3501

cochrane-simplification-train-3501

We included 70 RCTs with a total of 8461 participants randomised to either the intervention or control groups. The number of participants per trial ranged from 16 to 686. Fifty-five trials compared a behaviour-changing intervention with no treatment/usual care control and 15 evaluated the effectiveness of adding an additional component to a behaviour-changing intervention. Sixty-four trials were parallel RCTs, and four were cluster RCTs. Sixty-four trials were multicomponent, two were diet only and four were physical activity only interventions. Ten trials had more than two arms. The overall quality of the evidence was low or very low and 62 trials had a high risk of bias for at least one criterion. Total duration of trials ranged from six months to three years. The median age of participants was 10 years old and the median BMI z score was 2.2. Primary analyses demonstrated that behaviour-changing interventions compared to no treatment/usual care control at longest follow-up reduced BMI, BMI z score and weight. Mean difference (MD) in BMI was -0.53 kg/m2 (95% confidence interval (CI) -0.82 to -0.24); P < 0.00001; 24 trials; 2785 participants; low-quality evidence. MD in BMI z score was -0.06 units (95% CI -0.10 to -0.02); P = 0.001; 37 trials; 4019 participants; low-quality evidence and MD in weight was -1.45 kg (95% CI -1.88 to -1.02); P < 0.00001; 17 trials; 1774 participants; low-quality evidence. Thirty-one trials reported on serious adverse events, with 29 trials reporting zero occurrences RR 0.57 (95% CI 0.17 to 1.93); P = 0.37; 4/2105 participants in the behaviour-changing intervention groups compared with 7/1991 participants in the comparator groups). Few trials reported health-related quality of life or behaviour change outcomes, and none of the analyses demonstrated a substantial difference in these outcomes between intervention and control. In two trials reporting on minutes per day of TV viewing, a small reduction of 6.6 minutes per day (95% CI -12.88 to -0.31), P = 0.04; 2 trials; 55 participants) was found in favour of the intervention. No trials reported on all-cause mortality, morbidity or socioeconomic effects, and few trials reported on participant views; none of which could be meta-analysed. As the meta-analyses revealed substantial heterogeneity, we conducted subgroup analyses to examine the impact of type of comparator, type of intervention, risk of attrition bias, setting, duration of post-intervention follow-up period, parental involvement and baseline BMI z score. No subgroup effects were shown for any of the subgroups on any of the outcomes. Some data indicated that a reduction in BMI immediately post-intervention was no longer evident at follow-up at less than six months, which has to be investigated in further trials. Multi-component behaviour-changing interventions that incorporate diet, physical activity and behaviour change may be beneficial in achieving small, short-term reductions in BMI, BMI z score and weight in children aged 6 to 11 years. The evidence suggests a very low occurrence of adverse events. The quality of the evidence was low or very low. The heterogeneity observed across all outcomes was not explained by subgrouping. Further research is required of behaviour-changing interventions in lower income countries and in children from different ethnic groups; also on the impact of behaviour-changing interventions on health-related quality of life and comorbidities. The sustainability of reduction in BMI/BMI z score and weight is a key consideration and there is a need for longer-term follow-up and further research on the most appropriate forms of post-intervention maintenance in order to ensure intervention benefits are sustained over the longer term.

We found 70 randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups) comparing diet, physical activity, and behavioural (where habits are changed or improved) treatments to a variety of control groups delivered to 8461 overweight or obese children aged 6 to 11 years. We reported on the effects of 64 multicomponent interventions (different combinations of diet and physical activity and behaviour change), four physical activity interventions and two dietary interventions compared with no intervention, 'usual care’ or some other therapy if it was also delivered in the intervention arm. The children in the included studies were followed up between six months and three years. The average age of the children was 10 years. Most studies reported the body mass index (BMI) z score: BMI is a measure of body fat and is calculated by dividing weight (in kilograms) by the square of the body height measured in metres (kg/m²). In children, BMI is often measured in a way that takes into account sex and age, weight, and height changes as children grow older (BMI z score). We summarised the results of 37 trials in 4019 children reporting the BMI z score, which on average was 0.06 units lower in the intervention groups compared with the control groups. We summarised the results of 24 trials in 2785 children reporting BMI, which on average was 0.53 kg/m2 lower in the intervention groups compared with the control groups. We summarised the results of 17 trials in 1774 children reporting weight, which on average was 1.45 kg lower in the intervention groups compared with the control groups. Other effects of the interventions, such as improvements in health-related quality of life were less clear. No study investigated death from any cause, morbidity or socioeconomic effects. Serious adverse events were rare: only two of 31 trials with data reported any serious adverse events (4/2105 participants in the behaviour-changing intervention groups compared with 7/1991 participants in the comparator groups). This evidence is up to date as of July 2016. The overall quality of the evidence was low or very low, mainly because of limited confidence in how studies were performed, and the results were inconsistent between the studies. Also there were just a few studies for some outcomes, with small numbers of included children.

10.1002/14651858.CD012651

cochrane-simplification-train-3502

cochrane-simplification-train-3502

Twenty eight studies met our inclusion criteria. The majority of the studies were for the management of osteoporosis or low back pain, and most evaluated interventions aimed at health professionals. To improve the use of imaging in the management of osteoporosis, the effect of any type of intervention compared to no-intervention controls was modest (absolute improvement in bone mineral density test ordering +10%, IQR 0.0 to +27.7). Patient mediated, reminder, and organisational interventions appeared to have most potential for improving imaging use in osteoporosis. For low back pain studies, the most common intervention evaluated was distribution of educational materials and this showed varying effects. Other interventions in low back pain studies also showed variable effects. For other musculoskeletal conditions, distribution of educational materials, educational meetings and audit and feedback were not shown to be effective for changing imaging ordering behaviour. Across all conditions, increasing the number of intervention components did not increase effect. For improving the use of imaging in osteoporosis, most professional interventions demonstrated benefit, and patient mediated, reminder, and organisational interventions appeared to have most potential for benefit. For low back pain studies interventions showed varying effects. For other musculoskeletal conditions, no firm conclusions can be drawn.

Twenty eight studies met our inclusion criteria. The majority of studies evaluated interventions designed to change health professional behaviour, for example, the distribution of educational materials, reminders to health professionals and patient education. For improving the use of imaging in osteoporosis, most interventions aimed at health professionals demonstrated benefit, and patient mediated, reminder, and organisational interventions appeared to have most potential for benefit. For low back pain studies, the most common intervention evaluated was distribution of educational materials and this showed varying effects. Other interventions in low back pain studies showed variable effects. For other musculoskeletal conditions, distribution of educational materials, educational meetings and audit and feedback were not shown to be effective for changing imaging ordering behaviour. Across all conditions, increasing the number of intervention components did not result in a larger effect of interventions.

10.1002/14651858.CD006094.pub2

cochrane-simplification-train-3503

cochrane-simplification-train-3503

In our original review we included 15 studies with 1020 participants and excluded two. In this updated review we included seven new studies and excluded six, bringing the total number of included studies to 22 and involving 1732 participants. The control group intervention was the axillary block in 14 studies, supraclavicular block in six studies, mid-humeral block in two studies, and parascalene block in one study. One study compared ICB to both axillary and supraclavicular blocks. Nine studies employed ultrasound-guided ICB. The risk of failed surgical anaesthesia 30 minutes after block completion was similar for ICB and all other BPBs (11.4% versus 12.9%, risk ratio (RR) 0.88, 95% CI 0.51 to 1.52, P = 0.64), but tourniquet pain was less likely with ICB (11.9% versus 18.0%; RR of experiencing tourniquet pain 0.66, 95% CI 0.47 to 0.92, P = 0.02). Subgroup analysis by method of nerve localization, and by control group intervention, did not show any statistically significant differences in the risk of failed surgical anaesthesia. However when compared to a single-injection axillary block, ICB was better at providing complete sensory block of the musculocutaneous nerve (RR for failure 0.46, 95% CI 0.27 to 0.60, P < 0.0001). ICB had a slightly longer sensory block onset time (mean difference (MD) 1.9 min, 95% CI 0.2 to 3.6, P = 0.03) but was faster to perform than multiple-injection axillary (MD -2.7 min, 95% CI -3.4 to -2.0, P < 0.00001) or mid-humeral (MD -4.8 min, 95% CI -6.0 to -3.6, P < 0.00001) blocks. ICB is as safe and effective as any other BPBs, regardless of whether ultrasound or neurostimulation guidance is used. The advantages of ICB include a lower likelihood of tourniquet pain during surgery, more reliable blockade of the musculocutaneous nerve when compared to a single-injection axillary block, and a significantly shorter block performance time compared to multi-injection axillary and mid-humeral blocks.

We searched the databases until June 2013, and included 22 studies involving 1732 patients of whom 842 had an infraclavicular block and 930 had brachial plexus blockade with another technique. These other techniques were axillary block (injection in the armpit area; 14 studies), supraclavicular block (injection in the area just above the collarbone; six studies), mid-humeral block (injection in the upper arm; two studies) and parascalene block (injection in the lower neck area; one study). One study compared an infraclavicular block with both an axillary block and a supraclavicular block. The infraclavicular block had a high success rate and was as good as all other blocks in providing anaesthesia of the lower arm. Advantages of the infraclavicular block included a reduced risk of pain from the tourniquet applied to the upper arm during surgery and a faster performance time (four minutes on average) compared to more complex techniques of axillary or mid-humeral block that used three or four separate injections (instead of just one). Side-effects were uncommon, and no difference was seen between the infraclavicular block and all other blocks in this regard. In conclusion, this review showed that the infraclavicular block is an effective and safe choice for producing anaesthesia of the lower arm.

10.1002/14651858.CD005487.pub3

cochrane-simplification-train-3504

cochrane-simplification-train-3504

We identified six eligible studies in total. The six Included studies were generally of high quality, but the largest eligible study was excluded because of concerns about its validity. Study populations were statin naive, which led to a considerable loss of eligible participants. Five RCTs compared statin use with placebo or standard care. We pooled results from three studies, with a total of 178 participants, for mortality and non-fatal event outcomes. In the statin group, 7/105 (6.7%) participants died within 30 days of surgery, as did 10/73 (13.7%) participants in the control group. Only one death in each group was from cardiovascular causes, with an incidence of 0.95% in statin participants and 1.4% in control participants, respectively. All deaths occurred in a single study population, and so effect estimates were derived from one study only. The risk ratio (RR) of all-cause mortality in statin users showed a non-significant decrease in risk (RR 0.73, 95% CI 0.31 to 1.75). For cardiovascular death, the risk ratio was 1.05 (95% CI 0.07 to 16.20). Non-fatal MI within 30 days of surgery was reported in three studies and occurred in 4/105 (3.8%) participants in the statin group and 8/73 (11.0%) participants receiving placebo, for a non-significant decrease in risk (RR 0.47, 95% CI 0.15 to 1.52). Several studies reported muscle enzyme levels as safety measures, but only three (with a total of 188 participants) reported explicitly on clinical muscle syndromes, with seven events reported and no significant difference found between statin users and controls (RR 0.94, 95% CI 0.24 to 3.63). The only participant-reported outcome was nausea in one small study,with no significant difference in risk between groups. Two studies compared different doses of atorvastatin, with a total of 145 participants, but reported data were not sufficient to allow us to determine the effect of higher doses on any outcome. Evidence was insufficient to allow review authors to conclude that statin use resulted in either a reduction or an increase in any of the outcomes examined. The existing body of evidence leaves questions about the benefits of perioperative use of statins for vascular surgery unanswered. Widespread use of statins in the target population means that it may now be difficult for researchers to undertake the large RCTs needed to demonstrate any effect on the incidence of postoperative cardiovascular events. However, participant-reported outcomes have been neglected and warrant further study.

In July 2012 we searched medical databases for controlled trials of participants who had undergone aortic or arterial surgery and were randomly assigned to either statins or placebo (or standard care). Many vascular surgery patients are already taking statins; therefore we also included trials that randomly assigned participants to different doses of statin. Statin treatment should have been started any time between the decision to operate and performance of the operation and continued for at least 48 hours after the operation. We wanted to investigate the effect of this short-term statin therapy on the risk of death and cardiovascular events such as heart attack and stroke within 30 days of surgery. We also considered adverse effects of statins such as muscle pain. We found five studies that compared participants receiving statins with a control treatment or with placebo, but only three of these reported outcomes could be combined in the meta-analyses. These three studies were of high quality but studied only 178 participants in total. This means that evidence was insufficient to allow review authors to determine whether statins improved patient outcomes after surgery. We were also not able to establish whether any adverse effects such as muscle pain were associated with statin use. We found that two studies had compared different doses of atorvastatin, but evidence was insufficient to determine whether any benefits or risks were associated with using a higher dose. Given the limited quantity of data obtained from randomized controlled trials, further studies are required to allow investigators to gather better information about whether prescribing statins around the time of vascular surgery can improve outcomes. However, widespread use of statins in patients before they need surgery may make these studies impracticable.

10.1002/14651858.CD009971.pub2

cochrane-simplification-train-3505

cochrane-simplification-train-3505

Ten trials involving 10,479 participants were included. There was inconclusive evidence of an effect on the proportion of participants with index case management (defined as individuals tested, diagnosed and treated for CT or NG, or both) in the group with home-based (45/778, 5.8%) compared with clinic-based (51/788, 6.5%) specimen collection (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.60 to 1.29; 3 trials, I² = 0%, 1566 participants, moderate quality). Harms of home-based specimen collection were not evaluated in any trial. All 10 trials compared the proportions of individuals tested. The results for the proportion of participants completing testing had high heterogeneity (I² = 100%) and were not pooled. We could not combine data from individual studies looking at the number of participants tested because the proportions varied widely across the studies, ranging from 30% to 96% in home group and 6% to 97% in clinic group (low-quality evidence). The number of participants with positive test was lower in the home-based specimen collection group (240/2074, 11.6%) compared with the clinic-based group (179/967, 18.5%) (RR 0.72, 95% CI 0.61 to 0.86; 9 trials, I² = 0%, 3041 participants, moderate quality). Home-based specimen collection could result in similar levels of index case management for CT or NG infection when compared with clinic-based specimen collection. Increases in the proportion of individuals tested as a result of home-based, compared with clinic-based, specimen collection are offset by a lower proportion of positive results. The harms of home-based specimen collection compared with clinic-based specimen collection have not been evaluated. Future RCTs to assess the effectiveness of home-based specimen collection should be designed to measure biological outcomes of STI case management, such as proportion of participants with negative tests for the relevant STI at follow-up.

We searched the available literature for trials in which people were invited either to collect specimens at home or to attend a clinic for collection of specimens. We found 10 relevant trials in total. Three trials (including 1566 people) provided data to assess the proportion of people who completed testing, diagnosis and treatment. All trials gave information about the percentages of people who took self-collected specimens for detection of chlamydia and gonorrhoea infections at home and those who took the test at a clinic. Nine studies reported percentages related to positive test results. Trials in this review were funded by governmental or non-governmental organisations. There was no evidence of a difference between home-based and clinic-based specimen collection in the proportion of people who completed testing, diagnosis and treatment. In the home-based group 45 infections were detected and treated in a total of 778 people invited to collect specimens at home. In the clinic-based group 51 infections were detected and treated in a total of 788 people invited to attend a clinic. We could not combine data from individual studies looking at the number of participants tested because the proportions varied widely. A lower number of participants diagnosed in the home-based compared with the clinic-based group was documented. The potential harms of testing with home-collected specimens were not evaluated in any trial. The GRADE quality for the main outcomes was moderate (index case management, positive test prevalence) or low (proportion of individuals tested). The quality of evidence was downgraded because of methodological limitations in the studies. Home-based specimen collection could result in similar levels of index case management forChlamydia trachomatisorNeisseria gonorrhoeaeinfection when compared with clinic-based specimen collection. The safety of home-based specimen collection compared with clinic-based specimen collection have not been evaluated.

10.1002/14651858.CD011317.pub2

cochrane-simplification-train-3506

cochrane-simplification-train-3506

Four studies in 170 participants compared antidepressant therapy (fluoxetine, sertraline, citalopram or escitalopram) versus placebo or psychological training for 8 to 12 weeks. In generally very low or ungradeable evidence, compared to placebo, antidepressant therapy had no evidence of benefit on quality of life, had uncertain effects on increasing the risk of hypotension (3 studies, 144 participants: RR 1.72, 95% CI 0.75 to 3.92), headache (2 studies 56 participants: RR 2.91, 95% CI 0.73 to 11.57), and sexual dysfunction (2 studies, 101 participants: RR 3.83, 95% CI 0.63 to 23.34), and increased nausea (3 studies, 114 participants: RR 2.67, 95% CI 1.26 to 5.68). There were few or no data for hospitalisation, suicide or all-cause mortality resulting in inconclusive evidence. Antidepressant therapy may reduce depression scores during treatment compared to placebo (1 study, 43 participants: MD -7.50, 95% CI -11.94 to -3.06). Antidepressant therapy was not statistically different from group psychological therapy for effects on depression scores or withdrawal from treatment and a range of other outcomes were not measured. Despite the high prevalence of depression in dialysis patients and the relative priority that patients place on effective treatments, evidence for antidepressant medication in the dialysis setting is sparse and data are generally inconclusive. The relative benefits and harms of antidepressant therapy in dialysis patients are poorly known and large randomised studies of antidepressants versus placebo are required.

We included all studies which have looked at drug treatment against placebo (sugar pill) or other kinds of mental health support. People included in the studies had an equal chance of receiving either treatment. Unfortunately, even though depression is very common and finding good treatments for depression are highly valued by patients on dialysis, there are only a few small studies to tell us about whether drug treatments are both safe and reduce symptoms. Based on this information, we still don't know whether depression treatment works well for people treated with dialysis and is safe (doesn't cause excess and serious side effects). The question of whether drugs can reduce symptoms of depression and improve quality of life for people on dialysis is still important. We need a big study that involves dialysis patients and assesses a commonly-used antidepressant drug with a placebo and measures the treatment effects based on what patients and their families value most.

10.1002/14651858.CD004541.pub3

cochrane-simplification-train-3507

cochrane-simplification-train-3507

We included 244 randomised clinical trials with 28,619 participants that met our inclusion criteria. We considered all trials to be at high risk of bias. Two trials accounted for one-third of all included participants. The included participants were heterogenous with regard to disease (20 different medical specialties). The experimental interventions were parenteral nutrition (86 trials); enteral nutrition (tube-feeding) (80 trials); oral nutrition support (55 trials); mixed experimental intervention (12 trials); general nutrition support (9 trials); and fortified food (2 trials). The control interventions were treatment as usual (122 trials); no intervention (107 trials); and placebo (15 trials). In 204/244 trials, the intervention lasted three days or more. We found no evidence of a difference between nutrition support and control for short-term mortality (end of intervention). The absolute risk was 8.3% across the control groups compared with 7.8% (7.1% to 8.5%) in the intervention groups, based on the risk ratio (RR) of 0.94 (95% confidence interval (CI) 0.86 to 1.03, P = 0.16, 21,758 participants, 114 trials, low quality of evidence). We found no evidence of a difference between nutrition support and control for long-term mortality (maximum follow-up). The absolute risk was 13.2% in the control group compared with 12.2% (11.6% to 13%) following nutritional interventions based on a RR of 0.93 (95% CI 0.88 to 0.99, P = 0.03, 23,170 participants, 127 trials, low quality of evidence). Trial Sequential Analysis showed we only had enough information to assess a risk ratio reduction of approximately 10% or more. A risk ratio reduction of 10% or more could be rejected. We found no evidence of a difference between nutrition support and control for short-term serious adverse events. The absolute risk was 9.9% in the control groups versus 9.2% (8.5% to 10%), with nutrition based on the RR of 0.93 (95% CI 0.86 to 1.01, P = 0.07, 22,087 participants, 123 trials, low quality of evidence). At long-term follow-up, the reduction in the risk of serious adverse events was 1.5%, from 15.2% in control groups to 13.8% (12.9% to 14.7%) following nutritional support (RR 0.91, 95% CI 0.85 to 0.97, P = 0.004, 23,413 participants, 137 trials, low quality of evidence). However, the Trial Sequential Analysis showed we only had enough information to assess a risk ratio reduction of approximately 10% or more. A risk ratio reduction of 10% or more could be rejected. Trial Sequential Analysis of enteral nutrition alone showed that enteral nutrition might reduce serious adverse events at maximum follow-up in people with different diseases. We could find no beneficial effect of oral nutrition support or parenteral nutrition support on all-cause mortality and serious adverse events in any subgroup. Only 16 trials assessed health-related quality of life. We performed a meta-analysis of two trials reporting EuroQoL utility score at long-term follow-up and found very low quality of evidence for effects of nutritional support on quality of life (mean difference (MD) -0.01, 95% CI -0.03 to 0.01; 3961 participants, two trials). Trial Sequential Analyses showed that we did not have enough information to confirm or reject clinically relevant intervention effects on quality of life. Nutrition support may increase weight at short-term follow-up (MD 1.32 kg, 95% CI 0.65 to 2.00, 5445 participants, 68 trials, very low quality of evidence). There is low-quality evidence for the effects of nutrition support on mortality and serious adverse events. Based on the results of our review, it does not appear to lead to a risk ratio reduction of approximately 10% or more in either all-cause mortality or serious adverse events at short-term and long-term follow-up. There is very low-quality evidence for an increase in weight with nutrition support at the end of treatment in hospitalised adults determined to be at nutritional risk. The effects of nutrition support on all remaining outcomes are unclear. Despite the clinically heterogenous population and the high risk of bias of all included trials, our analyses showed limited signs of statistical heterogeneity. Further trials may be warranted, assessing enteral nutrition (tube-feeding) for different patient groups. Future trials ought to be conducted with low risks of systematic errors and low risks of random errors, and they also ought to assess health-related quality of life.

We included 244 trials, with 28,619 participants. The included trials assessed the effects of different kinds of nutrition support (i.e. dietary advice, enriching regular food with extra protein and calories, protein shakes, feeding through a catheter directly into a vein or through a tube directly into the stomach or gut). The nutrition support was provided to people in the trial who were ill with many different types of diseases and undergoing different procedures. What they all had in common was that they were at risk by at least one measure, including the trialists' clinical opinion. We found no evidence of a difference between nutrition support and control for risk of death. We found that 8.3% people died at short-term follow-up in the control groups compared with 7.8% in those who had been given nutritional support (low quality of evidence). At the longest point of follow-up 13.2% people in the control groups died compared with 12.2% in those who had been given nutritional support (low quality of evidence). We found no evidence of a difference between nutrition support and control for risk of a serious complications in the short term. People in the control groups had a serious complication rate of 9.9% at short-term follow-up compared with 9.2% with nutrition (low quality of evidence). At long-term follow-up 15.2% of people in the control groups had a serious complication compared with 13.8% in the nutrition groups (low quality of evidence). These results are based on just over 21,000 participants. Nutrition may increase weight by about 1.32 kg compared with people in the control groups. The increase in weight of 1.32 kg on average is of uncertain benefit. We could not reliably assess the effects on quality of life due to the variation in the reporting of this information. When we looked at the different types of nutrition support, a secondary analysis suggested that tube-feeding might be beneficial, reducing serious complications at maximum follow-up, but the strength of this finding is low. The evidence for our conclusions is of low quality for death and serious complications, and very low quality for weight. All trials had a high risk of bias (i.e. the trials were all conducted in a way that may overestimate the benefits and underestimate the harms of nutrition support). The results were consistent for death and serious complications, but there was a high level of variation in the effects on weight across the studies.

10.1002/14651858.CD011598.pub2

cochrane-simplification-train-3508

cochrane-simplification-train-3508

Five trials with 1838 randomised patients were included. There is some evidence for improved overall survival after treatment with purine antagonists compared to alkylators, but statistical significance was not reached (HR 0.89 [95% CI 0.78 to 1.01], 4 trials, N = 1638). However, the relative risk for achieving an overall response (RR 1.22 [95% CI 1.13 to 1.31], 5 trials, N = 1751) and complete remission (RR 1.94 [95% CI 1.65 to 2.28], 5 trials, N = 1751) was significantly higher, resulting in a longer progression-free survival (HR 0.70 [95% CI 0.61 to 0.82], 4 trials, N = 1638). Incidence of grade III/IV infections was significantly higher in patients receiving treatment with purine antagonists (RR 1.83 [95% 1.30 to 2.58], 4 trials, N = 1620). There was no significant difference concerning the relative risk for grade III/IV neutropenia (RR 1.14 [95% CI 0.98-1.34], 4 trials, N = 1620) and therapy-related mortality (RR 0.94 [95% CI 0.45 to 1.95]). Overall incidence of haemolytic anaemia was low, but significantly increased in the purine antagonist group (RR 3.36 [95% CI 1.27 to 8.91], 3 trials, N = 1258). Despite significantly increased overall response and complete remission rates and longer progression-free survival with first-line treatment of B-CLL patients with single-agent purine antagonists, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of purine antagonists also augments the risk for grade III/IV infections and haemolytic anaemia.

This review confirms the greater response rates achievable by using purine antagonists but at the cost of greater toxicity, mainly infections. There is inconclusive evidence whether treatment with purine antagonists improves survival. None of the studies included quality of life data. More research is needed to fully explore the role of purine antagonists in the treatment of B-CLL and their potential impact on survival.

10.1002/14651858.CD004270.pub2

cochrane-simplification-train-3509

cochrane-simplification-train-3509

Twenty two trials (3707 patients) were included. Hb ≥ 133 g/L was not associated with a reduction in the risk of all-cause mortality compared with 120 g/L in dialysis and pre-dialysis patients. In pre-dialysis patients, there was a significantly lower end of treatment creatinine clearance with Hb < 120 g/L compared to > 130 g/L (MD -4.17, 95% CI -6.33 to -2.02) but no significant difference in the risk of end-stage kidney disease (ESKD) (RR 1.05, 95% CI 0.50 to 2.22). Lower Hb targets resulted in an increased risk for seizures (RR 5.25, 95% CI 1.13 to 24.34) and a reduced risk of hypertensive episodes (RR 0.50, 95% CI 0.33 to 0.76). There were no significant differences in the risk of vascular access thrombosis. There was no significant difference in the risk of death for low (< 120 g/L) versus higher Hb targets (>133 g/L). Lower Hb targets were significantly associated with an increased risk for seizures but a reduced risk of hypertension. In general study quality was poor. There is a need for more adequately powered, well-designed and reported trials. Trials should be pragmatic, focusing on hard end-points (mortality, ESKD, major side effects) or outcomes which were previously not studied adequately (e.g. seizures, quality of life).

This review of clinical studies found that increasing haemoglobin to high levels lowered the chance of a person having a seizure, but increased blood pressure. Haemoglobin levels above 133 g/L did not reduce the risk of death in people with heart and kidney disease.

10.1002/14651858.CD003967.pub2

cochrane-simplification-train-3510

cochrane-simplification-train-3510

We included 41 articles reporting on 25 RCTs with 4404 participants. Risk of bias was low in 16 studies. Three studies involved workers with acute back pain, eight studies workers with subacute back pain, and 14 studies workers with chronic back pain. In 14 studies, physical conditioning as part of a return to work strategy was compared to usual care. The physical conditioning mostly consisted of graded activity with work-related exercises aimed at increasing back strength and flexibility, together with a set date for return to work. The programmes were divided into a light version with a maximum of five sessions, or an intense version with more than five sessions up to full time or as inpatient treatment. For acute back pain, there was low quality evidence that both light and intense physical conditioning programmes made little or no difference in sickness absence duration compared with care as usual at three to 12 months follow-up (3 studies with 340 workers). For subacute back pain, the evidence on the effectiveness of intense physical conditioning combined with care as usual compared to usual care alone was conflicting (four studies with 395 workers). However, subgroup analysis showed low quality evidence that if the intervention was executed at the workplace, or included a workplace visit, it may have reduced sickness absence duration at 12 months follow-up (3 studies with 283 workers; SMD -0.42, 95% CI -0.65 to -0.18). For chronic back pain, there was low quality evidence that physical conditioning as part of integrated care management in addition to usual care may have reduced sickness absence days compared to usual care at 12 months follow-up (1 study, 134 workers; SMD -4.42, 95% CI -5.06 to -3.79). What part of the integrated care management was most effective remained unclear. There was moderate quality evidence that intense physical conditioning probably reduced sickness absence duration only slightly compared with usual care at 12 months follow-up (5 studies, 1093 workers; SMD -0.23, 95% CI -0.42 to -0.03). Physical conditioning compared to exercise therapy showed conflicting results for workers with subacute and chronic back pain. Cognitive behavioural therapy was probably not superior to physical conditioning as an alternative or in addition to physical conditioning. The effectiveness of physical conditioning as part of a return to work strategy in reducing sick leave for workers with back pain, compared to usual care or exercise therapy, remains uncertain. For workers with acute back pain, physical conditioning may have no effect on sickness absence duration. There is conflicting evidence regarding the reduction of sickness absence duration with intense physical conditioning versus usual care for workers with subacute back pain. It may be that including workplace visits or execution of the intervention at the workplace is the component that renders a physical conditioning programme effective. For workers with chronic back pain physical conditioning has a small effect on reducing sick leave compared to care as usual after 12 months follow-up. To what extent physical conditioning as part of integrated care management may alter the effect on sick leave for workers with chronic back pain needs further research.

The evidence was current to March 2012. We analysed 17 comparisons of physical conditioning as part of a return to work strategy. Some trials examined physical conditioning in addition to care as usual versus care as usual only, and others compared physical conditioning to other types of interventions such as standard exercise therapy. Participants had either acute back pain (duration of symptoms less than six weeks), subacute back pain (duration of symptoms more than six but less than 12 weeks), or chronic back pain (duration of symptoms more than 12 weeks). Participants were followed for anywhere from three weeks to three years. We divided physical conditioning into light or intense, depending on its intensity and duration. Results showed that light physical conditioning has no effect on sickness absence duration for workers with subacute or chronic back pain. We found conflicting results for intense physical conditioning for workers with subacute back pain. Intense physical conditioning probably had a small effect on reducing sick leave at 12 months follow-up compared to usual care for workers with chronic back pain. Involving the workplace, or physical conditioning being part of integrated care management may have had a positive effect on reducing sick leave, but this needs further research. The quality of the evidence ranged from very low to moderate. Although 16 of the included studies were well designed and had no major flaws, some studies were poorly conducted and the small number of participants in most studies lowered the overall quality of the evidence.

10.1002/14651858.CD001822.pub3

cochrane-simplification-train-3511

cochrane-simplification-train-3511

We included 23 studies with 1250 participants that compared one drug with one or more other drugs. Of these comparisons, 19 studies compared propofol with another drug. Seven of these compared propofol with etomidate (four of which combined the drugs with remifentanil or fentanyl), five midazolam, six thiopentone and two sevoflurane. Three studies compared etomidate with thiopentone, and three etomidate with midazolam. Two studies compared thiopentone with midazolam, one thiopentone with diazepam and one midazolam with diazepam. Drug doses and the time over which the drugs were given varied between studies. Although all studies were described as randomized, limited information was provided about the methods used for selection and group allocation. A high level of performance bias was observed across studies, as study authors had not attempted to blind the anaesthetist to group allocation. Similarly, study authors had rarely provided sufficient information on whether outcome assessors had been blinded. Included studies presented outcome data for hypotension, apnoea, participant recall, success of cardioversion, minor adverse events of nausea and vomiting, pain at injection site and myoclonus, additional analgesia and participant satisfaction. We did not pool the data from different studies in view of the multiple drug comparisons, differences in definitions and reporting of outcomes, variability of endpoints and high or unclear risk of bias across studies. Few studies reported statistically significant results for our relevant outcomes, and most study authors concluded that both, or all, agents compared in individual studies were adequate for cardioversion procedures. It is our opinion that at present, there is no evidence to suggest that current anaesthetic practice for cardioversion should change.

Evidence is current to 27 March 2014. We found 23 relevant randomized controlled trials with 1250 participants undergoing cardioversion procedures. These studies compared one anaesthetic drug against one or more other drugs, including propofol, etomidate, thiopentone, sevoflurane, midazolam and diazepam. Study authors considered clinical outcomes such as decreased blood pressure, interrupted breathing and whether cardioversion was successful, as well as patient relevant outcomes such as recall, nausea and vomiting, pain on injection and satisfaction with the procedures. In addition to a variety of drug comparisons between studies, differences in study methods were described, with drugs given in different doses and over different lengths of time. These differences meant that it was inappropriate to combine the results of these studies. We believe that the quality of these studies was not sufficiently high, and that it would be misleading to combine the findings of all studies within this review. Study authors had not taken enough steps to reduce the risk of differences in methods within the studies, for example, by masking doctors and assessors regarding which drug was given to each patient. Most authors of individual studies concluded that all agents studied were adequate for making patients unaware during cardioversion. It is our opinion that at present, there is no evidence to suggest that drugs used by anaesthetists to make patients unaware of cardioversion should change.

10.1002/14651858.CD010824.pub2

cochrane-simplification-train-3512

cochrane-simplification-train-3512

We included three RCTs involving a total of 2303 participants: 1150 participants were randomized to receive TDC and 1153 participants were randomized to receive medical therapy. Overall, the risk of bias was regarded as high. The mean follow-up period of all three included trials was less than five years. Baseline characteristics (age, sex, and vascular risk factors) were similar across trials. Intention-to-treat analyses did not show a statistically significant risk reduction in the composite endpoint of recurrent stroke or TIA in the TDC group when compared with medical therapy (RR 0.73, 95% CI 0.45 to 1.17). A time-to-event analysis combining the results of two RCTs also failed to show a significant risk reduction with TDC (HR 0.69, 95% CI 0.43 to 1.13). When assessing stroke prevention alone, TDC still did not show a statistically significant benefit (RR 0.61, 95% CI 0.29 to 1.27) (HR 0.55, 95% CI 0.26 to 1.18). In a sensitivity analysis including the two studies using the Amplatzer PFO occluder, TDC showed a possible protective effect on recurrent stroke compared with medical therapy (HR 0.38, 95% CI 0.14 to 1.02); however, it did not reach statistical significance. Safety analysis found that the overall risks for all-cause mortality and adverse events were similar in both the TDC and medical therapy groups. However, TDC increased the risk of new-onset atrial fibrillation (RR 3.50, 95% CI 1.47 to 8.35) and may be associated with the type of device used. The combined data from recent RCTs have shown no statistically significant differences between TDC and medical therapy in the prevention of recurrent ischemic stroke. TDC closure was associated with an increased risk of atrial fibrillation but not with serious adverse events.

The evidence is current to July 2014. We included in our analysis three multicenter randomized trials involving a total of 2303 participants. All three trials recruited participants aged 60 years or younger with a cryptogenic stroke or minor stroke and had a PFO diagnosed by specialist heart scan. 1150 participants were randomized to the TDC group where the procedure was performed with the Amplatzer device in two studies, and with the STARFlex device in one study. The mean follow-up period of all three included trials was less than five years. Two studies were sponsored by St Jude Medical and one study was sponsored by NMT Medical. We found that, when compared with medical therapy, TDC failed to show any significant benefit in reducing the risk of recurrent stroke or similar events. However, there was a possible protective effect on recurrent strokes in those participants for whom an Amplatzer device was used compared with medical therapy. We did not find evidence that TDC increased the rate of serious adverse events overall. However, TDC increased the risk of new-onset atrial fibrillation (where there is a problem with the rate or rhythm of the heartbeat) and may be associated with the type of device used. We performed this systematic review of three randomized trials to compare both the safety and efficacy of TDC with medical therapy on recurrent cerebrovascular events in people with cryptogenic stroke and PFO following theCochrane Handbook for Systematic Reviews of Interventions.The major problem in terms of risk of bias is the high dropout rate compared with event rate in these three trials and different dropout rates between groups. Meanwhile, we lack individual-level data for analysis. Although there is a suggestion of potential benefit with the Amplatzer device closure in preventing recurrent stroke, our findings still need to be confirmed in further studies.

10.1002/14651858.CD009938.pub2

cochrane-simplification-train-3513

cochrane-simplification-train-3513

We included 19 studies (1756 participants). We selected only randomized, placebo-controlled, double-blinded studies to minimize inclusion of poor quality studies. However, the risk of bias in the included studies was not formally assessed. Children receiving a single intraoperative dose of dexamethasone (dose range = 0.15 to 1.0 mg/kg) were half as likely to vomit in the first 24 hours compared to children receiving placebo (risk ratio (RR) 0.49; 95% confidence interval (CI) 0.41 to 0.58; P < 0.00001). Routine use in five children would be expected to result in one less patient experiencing post-tonsillectomy emesis (risk difference (RD) -0.24; 95% CI -0.32 to -0.15; P < 0.00001). Children receiving dexamethasone were also more likely to advance to a soft/solid diet on post-tonsillectomy day one (RR 1.45; 95% CI 1.15 to 1.83; P = 0.001) than those receiving placebo. Finally, postoperative pain was improved in children receiving dexamethasone as measured by a visual analog scale (VAS, 0 to 10) (MD -1.07; 95% CI -1.73 to -0.41; P = 0.001), which correlates clinically to a reduction in pain (on a VAS of 0 to 10) from 4.72 to 3.65. No adverse events were noted in the included studies. The evidence suggests that a single intravenous dose of dexamethasone is an effective, safe and inexpensive treatment for reducing morbidity from pediatric tonsillectomy.

We included 19 randomized controlled trials in the review, with a total of 1756 patients. The review of trials found that a dose of corticosteroid during tonsillectomy or adenotonsillectomy can prevent vomiting for one out of every five children who gets the drug. Children also return to a normal diet more quickly and they have less pain after surgery.

10.1002/14651858.CD003997.pub2

cochrane-simplification-train-3514

cochrane-simplification-train-3514

Two studies with a total of 84 participants were included: a 12-month RCT of early rehabilitation in adults of mean age 72 years conducted in two centres in England (UK) and a six-month proof-of-concept RCT of an expert patient programme (EPP) in adults of mean age 60 years in a single regional respiratory centre in Northern Ireland (UK). The EPP was delivered in group format once a week for eight weeks using standardised EPP materials plus disease-specific education including airway clearance techniques, dealing with symptoms, exacerbations, health promotion and available support. We did not find any studies that included children. Data aggregation was not possible and findings are reported narratively in the review. For the primary outcomes, both studies reported health-related quality of life, as measured by the St George's Respiratory Questionnaire (SGRQ), but there was no clear evidence of benefit. In one study, the mean SGRQ total scores were not significantly different at 6 weeks', 3 months' and 12 months' follow-up (12 months mean difference (MD) -10.27, 95% confidence interval (CI) -45.15 to 24.61). In the second study there were no significant differences in SGRQ. Total scores were not significantly different between groups (six months, MD 3.20, 95% CI -6.64 to 13.04). We judged the evidence for this outcome as low or very low. Neither of the included studies reported data on exacerbations requiring antibiotics. For serious adverse events, one study reported more deaths in the intervention group compared to the control group, (intervention: 4 of 8, control: 2 of 12), though interpretation is limited by the low event rate and the small number of participants in each group. For our secondary outcomes, there was no evidence of benefit in terms of frequency of hospital admissions or FEV1 L, based on very low-quality evidence. One study reported self-efficacy using the Chronic Disease Self-Efficacy scale, which comprises 10 components. All scales showed significant benefit from the intervention but effects were only sustained to study endpoint on the Managing Depression scale. Further details are reported in the main review. Based on overall study quality, we judged this evidence as low quality. Neither study reported data on respiratory symptoms, economic costs or adverse events. There is insufficient evidence to determine whether self-management interventions benefit people with bronchiectasis. In the absence of high-quality evidence it is advisable that practitioners adhere to current international guidelines that advocate self-management for people with bronchiectasis. Future studies should aim to clearly define and justify the specific nature of self-management, measure clinically important outcomes and include children as well as adults.

We conducted a search on 13 December 2017 and found just two UK studies that included 84 participants, comparing a self-management approach with normal care for adults with bronchiectasis. One study looked at the impact of an expert patient self-management programme and the other, involving just a small number of participants with bronchiectasis, looked at self-management in combination with exercises to improve lung function. Neither study included children. Health-related quality of life did not improve in either study. Although there were more deaths in the group receiving self-management in one study, the numbers were very small and we do not know whether the difference is meaningful. The number of admissions to hospital, and lung function showed no benefit from self-management. In one of the studies, people receiving self-management felt more empowered to manage their condition. There was no information on the impact of self-management on symptoms of bronchiectasis, adverse events or potential cost savings arising from more effective self-management. There are no studies looking at self-management in children. Overall there is not enough information to assess whether strategies to support self-management may help people with bronchiectasis and further studies are needed. Future studies will need to look at how often flare ups occur, how often antibiotics are prescribed, and how long for, whether people have a better quality of life, and the impact of self-management on costs of care. It is also important to look at self-management for bronchiectasis in children. This review is based on only two small trials and the quality of the studies is very poor. With only two studies looking at very specific approaches to self-management we cannot say with any degree of certainty whether self-management strategies work for people with bronchiectasis, but until further evidence is available we advocate adherence to current international guidelines that recommend self-management for people with bronchiectasis.

10.1002/14651858.CD012528.pub2

cochrane-simplification-train-3515

cochrane-simplification-train-3515

We included 21 studies (6016 participants) in this review. Trimethoprim-sulfamethoxazole (TMP-SMX) was as effective as fluoroquinolones in achieving short-term (RR 1.00, 95% CI 0.97 to 1.03) and long-term (RR 0.99, 95% CI 0.94 to 1.05) symptomatic cure. Beta-lactam drugs were as effective as TMP-SMX for short-term (RR 0.95, 95% CI 0.81 to 1.12) and long-term (RR 1.06, 95% CI 0.93 to 1.21) symptomatic cure. Short-term cure for nitrofurantoin was similar to that of TMP-SMX (RR 0.99, 95% CI 0.95 to 1.04) as was long-term symptomatic cure (RR 1.01, 95% CI 0.94 to 1.09). Fluoroquinolones were more effective than beta-lactams (RR 1.22, 95% CI 1.13 to 1.31) for short-term bacteriological cure. Rashes were more frequent in patients treated with TMP-SMX than with nitrofurantoin or fluoroquinolones and in patients treated with beta-lactam drugs compared to fluoroquinolones. Minimal data were available on the emergence of resistant strains during or after antimicrobial treatment. No differences were observed between the classes of antimicrobials included in this review for the symptomatic cure of acute uncomplicated UTI. Fluoroquinolones proved more effective than beta-lactams for the short-term bacteriological outcome, probably with little clinical significance. Individualised treatment should take into consideration the predictable susceptibility of urinary pathogens in local areas, possible adverse events and resistance development, and patient preference.

Twenty one good quality studies, enrolling 6016 participants, which used different classes of antimicrobials for treating acute cystitis in women for 3 up to 10 days, were included in this review. The classes of antimicrobials included in the review proved equally effective for the symptomatic cure. Fluoroquinolones proved more effective than beta-lactams for the short-term bacteriological cure, but the significance of this finding is doubtful. Fewer rashes developed in patients treated with fluoroquinolones. Nitrofurantoin caused fewer rashes than TMP-SMX while having similar rates of any adverse events. Given the small number of studies included in each comparison and for each outcome it is recommended that further randomised controlled trials be conducted.

10.1002/14651858.CD007182.pub2

cochrane-simplification-train-3516

cochrane-simplification-train-3516

We included a single-centre non-blinded randomised controlled trial that reported a total of 302 intubation attempts in 232 infants. The median gestational age of enrolled infants was 29 weeks. Paediatric residents and fellows performed the intubations. We judged the study to be at low risk of bias overall. Investigators compared success rates of first-attempt intubation with and without use of a stylet and reported success rates as similar between stylet and no-stylet groups (57% and 53%) (P = 0.47). Success rates did not differ between groups in subgroup analyses by provider level of training and infant weight. Results showed no differences in secondary review outcomes, including duration of intubation, number of attempts, participant instability during the procedure, and local airway trauma. Only 25% of all intubations took less than 30 seconds to perform. Study authors did not report neonatal morbidity nor mortality. We considered the quality of evidence as low on GRADE analysis, given that we identified only one unblinded study. Current available evidence suggests that use of a stylet during neonatal orotracheal intubation does not significantly improve the success rate among paediatric trainees. However, only one brand of stylet and one brand of endotracheal tube have been tested, and researchers performed all intubations on infants in a hospital setting. Therefore, our results cannot be generalised beyond these limitations.

In literature searches updated in April 2017, we found one randomised controlled trial (302 intubations) that met the inclusion criteria of this review. Rates of successful intubation at first attempt with or without use of a stylet as an aid were similar, at 57% and 53%, respectively. Success rates with and without use of a stylet did not differ between infants of different weights, or between trainee paediatric doctors with different levels of experience. The length of time it took to intubate and the number of attempts made before successful intubation were comparable between groups. The incidence of a drop in a patient’s oxygen level and in heart rate was equivalent between groups, as was the reported incidence of trauma to the airway associated with the procedure. The quality of evidence was low. We downgraded the level because we included only one unblinded study.

10.1002/14651858.CD011791.pub2

cochrane-simplification-train-3517

cochrane-simplification-train-3517

For abdominal wall lift with pneumoperitoneum versus pneumoperitoneum, a total of 130 participants (all with low anaesthetic risk) scheduled for elective laparoscopic cholecystectomy were randomised in five trials to abdominal wall lift with pneumoperitoneum (n = 53) versus pneumoperitoneum only (n = 52). One trial which included 25 people did not state the number of participants in each group. All five trials had a high risk of bias. There was no mortality or conversion to open cholecystectomy in any of the participants in the trials that reported these outcomes. There was no significant difference in the rate of serious adverse events between the two groups (two trials; 2/29 events (0.069 events per person) versus 2/29 events (0.069 events per person); rate ratio 1.00; 95% CI 0.17 to 5.77). None of the trials reported quality of life, the proportion of people discharged as day-patient laparoscopic cholecystectomies, or pain between four and eight hours after the operation. There was no significant difference in the operating time between the two groups (four trials; 53 participants versus 54 participants; 13.39 minutes longer (95% CI 2.73 less to 29.51 minutes longer) in the abdominal wall lift with pneumoperitoneum group and 100 minutes in the pneumoperitoneum group). For abdominal wall lift versus pneumoperitoneum, a total of 774 participants (the majority with low anaesthetic risk) scheduled for elective laparoscopic cholecystectomy were randomised in 18 trials to abdominal wall lift without pneumoperitoneum (n = 332) versus pneumoperitoneum (n = 358). One trial which included 84 people did not state the number in each group. All the trials had a high risk of bias. There was no mortality in any of the trials that reported this outcome. There was no significant difference in the proportion of participants with serious adverse events (six trials; 5/172 (weighted proportion 2.4%) versus 2/171 (1.2%); RR 2.01; 95% CI 0.52 to 7.80). There was no significant difference in the rate of serious adverse events between the two groups (three trials; 5/99 events (weighted number of events per person = 0.346 events) versus 2/99 events (0.020 events per person); rate ratio 1.73; 95% CI 0.35 to 8.61). None of the trials reported quality of life or pain between four and eight hours after the operation. There was no significant difference in the proportion of people who underwent conversion to open cholecystectomy (11 trials; 5/225 (weighted proportion 2.3%) versus 7/235 (3.0%); RR 0.76; 95% CI 0.26 to 2.21). The operating time was significantly longer in the abdominal wall lift group than in the pneumoperitoneum group (16 trials; 6.87 minutes longer (95% CI 4.74 minutes to 9.00 minutes longer) in the abdominal wall lift group versus 75 minutes in the pneumoperitoneum group). There was no significant difference in the proportion of people discharged as laparoscopic cholecystectomy day-patients (two trials; 15/31 (weighted proportion 48.5%) versus 9/31 (29%); RR 1.67; 95% CI 0.85 to 3.26). Abdominal wall lift with or without pneumoperitoneum does not seem to offer an advantage over pneumoperitoneum in any of the patient-oriented outcomes for laparoscopic cholecystectomy in people with low anaesthetic risk. Hence it cannot be recommended routinely. The safety of abdominal wall lift is yet to be established. More research on the topic is needed because of the risk of bias in the included trials and because of the risk of type I and type II random errors due to the few participants included in the trials. Future trials should include people at higher anaesthetic risk. Furthermore, such trials should include blinded assessment of outcomes.

A total of 130 participants (all with low anaesthetic risk) were included in five trials which compared abdominal wall lift combined with very low pressure pneumoperitoneum and standard pneumoperitoneum. All five trials had a high risk of bias (introducing the possibility of overestimating benefits or underestimating the harms of abdominal wall lift). No-one died as a result of surgery. There was no significant difference in the rate of serious complications related to the surgery. None of the trials reported quality of life, the proportion of people discharged as laparoscopic cholecystectomy day-patients, or pain between four and eight hours after the operation. None required conversion of key-hole surgery to an open operation using a larger incision. There was no significant difference in the operating time between the two groups. Abdominal wall lift versus pneumoperitoneum A total of 774 participants (the majority with low anaesthetic risk) who underwent planned laparoscopic cholecystectomy were included in 18 trials which compared abdominal wall lift and standard pneumoperitoneum. All the trials had a high risk of bias. No-one died as a result of the surgery. There was no significant difference in the rate of serious complications related to surgery. None of the trials reported quality of life or pain between four and eight hours after the operation. There was no significant difference in the rate of serious adverse events, the proportion of people who underwent an open operation using a larger incision, or the proportion discharged on the same day of surgery. The operating time was about seven minutes longer on average if the operation was performed using abdominal wall lift rather than pneumoperitoneum. In summary, abdominal wall lift does not seem to offer an advantage over pneumoperitoneum in any of the patient-oriented outcomes for laparoscopic cholecystectomy in people with low anaesthetic risk. Abdominal wall lift may increase costs by increasing the operating time. Hence it cannot be recommended routinely. The safety of abdominal wall lift is yet to be established. More randomised clinical trials on the topic are needed since the possibility of arriving at erroneous conclusions due to bias and due to the play of chance was high because of the design of the trials. Future trials should include people at high risk during anaesthesia. Furthermore, such trials should employ blinded assessments of outcome measures.

10.1002/14651858.CD006574.pub4

cochrane-simplification-train-3518

cochrane-simplification-train-3518

We included 13 studies, with a total 467 participants, testing a range of different interventions. Outcome measures included 36 measures of sensory impairment and 13 measures of upper limb function. All but two studies had unclear or high risk of bias. While there is insufficient evidence to reach conclusions about the effects of interventions included in this review, three studies provided preliminary evidence for the effects of some specific interventions, including mirror therapy for improving detection of light touch, pressure and temperature pain; a thermal stimulation intervention for improving rate of recovery of sensation; and intermittent pneumatic compression intervention for improving tactile and kinesthetic sensation. We could not perform meta-analysis due to a high degree of clinical heterogeneity in both interventions and outcomes. Multiple interventions for upper limb sensory impairment after stroke are described but there is insufficient evidence to support or refute their effectiveness in improving sensory impairment, upper limb function, or participants' functional status and participation. There is a need for more well-designed, better reported studies of sensory rehabilitation.

We found 13 studies involving 467 participants that tested different treatments for sensory loss. There is limited evidence that these treatments may be effective. No more than one study examined each particular intervention, frequently the studies were of poor quality and lacked sufficient information. Further research is needed before clear recommendations can be made.

10.1002/14651858.CD006331.pub2

cochrane-simplification-train-3519

cochrane-simplification-train-3519

Nine trials involving 1822 patients with bleeding haemorrhoids were identified. The included trials were generally not of high quality and used one TCMH preparation compared with another TCMH preparation (Type I) (five trials) or western medicines (Type II) (four trials). We could not pool the data to perform a meta-analysis as only two of the included trials used the same intervention or comparison. In the nine trials, TCMHs showed a statistically significant difference for the improvement in the general curative effects or total grade of symptoms in six trials (P < 0.05; P < 0.01), of hematochezia in three trials (P < 0.05; P < 0.001), and of inflammation of perianal mucosa in one trial (P < 0.05). The adverse effects reported were not serious and were scarce. This review did not provide strong evidence concerning the effectiveness of TCMHs for stopping bleeding from haemorrhoids. Most of the included studies were of low quality and there was a scarcity of eligible trials and numbers of participants. Limited, weak evidence showed that some herbal formulae, when including Radix Sanguisorbae, Radix Rehmanniae, Fructus Sophorae, Radix Angelicae Sinensis, Radix Scutellariae, etc., may alleviate some symptoms caused by haemorrhoids. These include hematochezia, congestive haemorrhoidal cushions and inflammation of perianal mucosa in the short term. Well-designed clinical trials are required urgently before any confident conclusions can be drawn about the value of TCMHs for stopping bleeding from haemorrhoids. At present, the evidence is not enough that clinical practice should be changed immediately on the basis of these results.

However, our primary research for this review showed that there was no strong evidence concerning the effectiveness of TCMHs in stopping bleeding from haemorrhoids. The included studies were few and of low quality. Limited, weak evidence showed that some formulae, when including Radix Sanguisorbae, Radix Rehmanniae, Fructus Sophorae, etc., may alleviate some symptoms caused by haemorrhoids. These symptoms include hematochezia and congestive haemorrhoidal cushions, in the short term. Additional, standardised trials are needed for meta-analysis to draw a final conclusion.

10.1002/14651858.CD006791.pub2

cochrane-simplification-train-3520

cochrane-simplification-train-3520

We included two RCTs (1167 participants). The first RCT compared zoledronic acid with placebo in 96 men undergoing pelvic radiotherapy for non-metastatic prostate cancer. The second RCT had four treatment arms, two of which evaluated zoledronic acid plus adjuvant androgen suppression compared with androgen suppression only in 1071 men undergoing pelvic radiotherapy for non-metastatic prostate cancer. Both studies were at a moderate to high risk of bias and all evidence was judged to be of very low certainty. The studies provided no evidence on the primary outcomes of the review and provided limited data in relation to secondary outcomes, such that meta-analyses were not possible. Both studies focused on interventions to improve bone health in relation to androgen deprivation rather than radiation-related insufficiency fractures and avascular necrosis. Few fractures were described in each study and those described were not specific to insufficiency fractures secondary to radiotherapy. Both studies reported that zoledronic acid in addition to androgen deprivation and pelvic radiotherapy led to improvements in BMD; however, the changes in BMD were measured and reported differently. There was no available evidence regarding adverse effects. The evidence relating to interventions to prevent insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults is of very low certainty. This review highlights the need for prospective clinical trials using interventions prior to and during radiotherapy to prevent radiation-related bone morbidity, insufficiency fractures and avascular necrosis. Future trials could involve prospective assessment of bone health including BMD and bone turnover markers prior to pelvic radiotherapy. The interventions for investigation could begin as radiotherapy commences and remain ongoing for 12 to 24 months. Bone turnover markers and BMD could be used as surrogate markers for bone health in addition to radiographic imaging to report on presence of insufficiency fractures and development of avascular necrosis. Clinical assessments and patient reported outcomes would help to identify any associated adverse effects of treatment and quality of life outcomes.

We found two studies where people were randomly put into one of two or more treatment groups (called randomised controlled trials) which were sufficiently relevant to the review topic. Both studies, which involved 1167 participants altogether, were conducted in men undergoing radiotherapy for prostate cancer and evaluated a bisphosphonate medicine called zoledronic acid. These men also received hormone treatment for their condition as reduced bone mineral density (BMD; how many minerals are in the bones, which determines how solid and strong the bones are) is a known side effect of this treatment. Studies measured and reported outcomes differently and we were unable to pool their results (data); however, limited evidence suggested that zoledronic acid might improve BMD in this specific group (men with prostate cancer) who received both hormone treatment and radiotherapy. There were few fractures or avascular necrosis events in the studies, therefore, it is very uncertain whether zoledronic acid has an impact on these important outcomes. As the studies were not specifically designed to evaluate the effect of zoledronic acid on radiotherapy-related bone outcomes, and participants also received hormone treatment, it is very uncertain whether the evidence applies to people undergoing pelvic radiotherapy for other cancers and people not receiving adjuvant hormone treatment. Both studies were at a moderate to high risk of bias and all evidence was judged to be of very low certainty. There is insufficient evidence that zoledronic acid and other medicines prevent radiotherapy-induced bone complications. This review highlights the need for clinical trials using interventions prior to and during radiotherapy to prevent radiation-related bone morbidity, insufficiency fractures and avascular necrosis.

10.1002/14651858.CD010604.pub2

cochrane-simplification-train-3521

cochrane-simplification-train-3521

The overall quality of the evidence was very low. In this update no new studies were identified for inclusion; one additional study was excluded. Of the two small included studies, one study showed a non-significant effect of calcitonin on the number of patients with complete pain relief (risk ratio (RR) 2.50; 95% confidence interval (CI) 0.55 to 11.41). The second study provided no evidence that calcitonin reduced analgesia consumption (RR 1.05; 95% CI 0.90 to 1.21) in patients with painful bone metastases. There was no evidence that calcitonin was effective in controlling complications due to bone metastases, for improving quality of life or for patients' survival. Although not statistically significant, a greater number of adverse effects were observed in the groups given calcitonin in the two included studies (RR 3.50; 95% CI 0.77 to 15.88). Current available research evidence is of very low quality and there is a lack of evidence to support the use of calcitonin for managing bone pain from bone metastases. Since the last version of this review, we did not identify any additional studies.

This review looked at the effectiveness of calcitonin for controlling pain from bone metastases. However, only two studies were found with very low quality evidence to support the use of calcitonin for patients suffering from bone pain. We updated the review in 2015 and did not find any more studies. There were slightly more side effects for the patients given calcitonin. Unless new studies provide additional relevant information about this treatment, other therapeutic approaches should be considered.

10.1002/14651858.CD003223.pub2

cochrane-simplification-train-3522

cochrane-simplification-train-3522

We included 30 trials, with a total of 1569 participants, in this review. We included trials of ventilator mode or type, earplugs or eye masks or both, massage, relaxation interventions, foot baths, music interventions, nursing interventions, valerian acupressure, aromatherapy, and sound masking. Outcomes included objective sleep outcomes, subjective sleep quality and quantity, risk of delirium, participant satisfaction, length of ICU stay, and adverse events. Clinical heterogeneity (e.g., participant population, outcomes measured) and research design limited quantitative synthesis, and only a small number of studies were available for most interventions. The quality of the evidence for an effect of non-pharmacological interventions on any of the outcomes examined was generally low or very low. Only three trials, all of earplugs or eye masks or both, provided data suitable for two separate meta-analyses. These meta-analyses, each of two studies, showed a lower incidence of delirium during ICU stay (risk ratio 0.55, 95% confidence interval (CI) 0.38 to 0.80, P value = 0.002, two studies, 177 participants) and a positive effect of earplugs or eye masks or both on total sleep time (mean difference 2.19 hours, 95% CI 0.41 to 3.96, P value = 0.02, two studies, 116 participants); we rated the quality of the evidence for both of these results as low. There was also some low quality evidence that music (350 participants; four studies) may improve subjective sleep quality and quantity, but we could not pool the data. Similarly, there was some evidence that relaxation techniques, foot massage, acupressure, nursing or social intervention, and sound masking can provide small improvements in various subjective measures of sleep quality and quantity, but the quality of the evidence was low. The effects of non-pharmacological interventions on objective sleep outcomes were inconsistent across 16 studies (we rated the quality of the evidence as very low): the majority of studies relating to the use of earplugs and eye masks found no benefit; results from six trials of ventilator modes suggested that certain ventilator settings might offer benefits over others, although the results of the individual trials did not always agree with each other. Only one study measured length of stay in the ICU and found no significant effect of earplugs plus eye masks. No studies examined the effect of any non-pharmacological intervention on mortality, risk of post-traumatic stress disorder, or cost-effectiveness; the included studies did not clearly report adverse effects, although there was very low quality evidence that ventilator mode influenced the incidence of central apnoeas and patient-ventilator asynchronies. The quality of existing evidence relating to the use of non-pharmacological interventions for promoting sleep in adults in the ICU was low or very low. We found some evidence that the use of earplugs or eye masks or both may have beneficial effects on sleep and the incidence of delirium in this population, although the quality of the evidence was low. Further high-quality research is needed to strengthen the evidence base.

We found 30 trials, with a total of 1569 participants, and the interventions included changes to ventilator type and settings, earplugs and eye masks, relaxation therapy, sleep-inducing music, massage, foot baths, aromatherapy, valerian acupressure, sound masking, and changing the visiting times of family members. We assessed the effects of these interventions on sleep outcomes (e.g., quality and amount of sleep), length of stay in the ICU, the occurrence of delirium, other adverse events, and death. Overall, the quality of the evidence for an effect of the interventions on any of the outcomes was low or very low. Normally, we would try to pool findings from similar trials of each intervention, but this was difficult because the design of the trials varied greatly. We were able to combine the results from three trials of earplugs and eye masks and found that their use increased the number of hours slept and prevented delirium in adults in the ICU. However, we cannot be certain about these findings because of problems with how the trials were carried out. There was also some low quality evidence from four studies that music may improve subjective sleep quality and quantity, but we could not pool the data. Similarly, a low number of studies found that relaxation techniques, foot massage, acupressure, nursing or social intervention, and sound masking can provide small improvements in participant-reported or nurse-assessed sleep quality and quantity, but the quality of the evidence was low. The effects of the interventions on objective sleep outcomes (e.g., sleep measured by a machine) varied: the majority of studies that looked at the use of earplugs and eye masks found no benefit, and although the results from six trials of ventilator modes suggested that certain ventilator settings might offer benefits over others, the results of the individual trials did not always agree with each other. Only one study measured length of stay in the ICU and found no significant effect of earplugs plus eye masks. None of the included studies looked at economic outcomes, risk of post-traumatic stress disorder, or deaths. The trials did not clearly report adverse effects, although there was very low quality evidence that ventilator mode might influence certain adverse effects that can happen when people are on a ventilator. In summary, further well-designed and conducted research is needed to strengthen the evidence for the use of these interventions for improving sleep in critically ill adults.

10.1002/14651858.CD008808.pub2

cochrane-simplification-train-3523

cochrane-simplification-train-3523

Fifty-six trials met the inclusion criteria; 51 trials involving 4624 participants provided data for meta-analysis. Five trials were at low risk of bias, five at high and 46 at unclear risk of bias. There is moderate quality evidence that powered toothbrushes provide a statistically significant benefit compared with manual toothbrushes with regard to the reduction of plaque in both the short term (standardised mean difference (SMD) -0.50 (95% confidence interval (CI) -0.70 to -0.31); 40 trials, n = 2871) and long term (SMD -0.47 (95% CI -0.82 to -0.11; 14 trials, n = 978). These results correspond to an 11% reduction in plaque for the Quigley Hein index (Turesky) in the short term and 21% reduction long term. Both meta-analyses showed high levels of heterogeneity (I2 = 83% and 86% respectively) that was not explained by the different powered toothbrush type subgroups. With regard to gingivitis, there is moderate quality evidence that powered toothbrushes again provide a statistically significant benefit when compared with manual toothbrushes both in the short term (SMD -0.43 (95% CI -0.60 to -0.25); 44 trials, n = 3345) and long term (SMD -0.21 (95% CI -0.31 to -0.12); 16 trials, n = 1645). This corresponds to a 6% and 11% reduction in gingivitis for the Löe and Silness index respectively. Both meta-analyses showed high levels of heterogeneity (I2 = 82% and 51% respectively) that was not explained by the different powered toothbrush type subgroups. The number of trials for each type of powered toothbrush varied: side to side (10 trials), counter oscillation (five trials), rotation oscillation (27 trials), circular (two trials), ultrasonic (seven trials), ionic (four trials) and unknown (five trials). The greatest body of evidence was for rotation oscillation brushes which demonstrated a statistically significant reduction in plaque and gingivitis at both time points. Powered toothbrushes reduce plaque and gingivitis more than manual toothbrushing in the short and long term. The clinical importance of these findings remains unclear. Observation of methodological guidelines and greater standardisation of design would benefit both future trials and meta-analyses. Cost, reliability and side effects were inconsistently reported. Any reported side effects were localised and only temporary.

Authors from the Cochrane Oral Health Group carried out this review of existing studies and the evidence is current up to 23 January 2014. It includes 56 studies published from 1964 to 2011 in which 5068 participants were randomised to receive either a powered toothbrush or a manual toothbrush. Majority of the studies included adults, and over 50% of the studies used a type of powered toothbrush that had a rotation oscillation mode of action (where the brush head rotates in one direction and then the other). The evidence produced shows benefits in using a powered toothbrush when compared with a manual toothbrush. There was an 11% reduction in plaque at one to three months of use, and a 21% reduction in plaque when assessed after three months of use. For gingivitis, there was a 6% reduction at one to three months of use and an 11% reduction when assessed after three months of use. The benefits of this for long-term dental health are unclear. Few studies reported on side effects; any reported side effects were localised and only temporary. The evidence relating to plaque and gingivitis was considered to be of moderate quality.

10.1002/14651858.CD002281.pub3

cochrane-simplification-train-3524

cochrane-simplification-train-3524

Seven studies mostly with small sample sizes, comparing 4 different interventions (prostaglandins alone, mifepristone alone, and mifepristone/misoprostol and methotrexate/misoprostol versus vacuum aspiration) were included. Results are sometimes based on one trial only. Prostaglandins vs vacuum aspiration: the rate of abortions not completed with the intended method was statistically significant higher in the prostaglandin group (2.7, 95% CI 1.1 to 6.8) compared to surgery. There are no data on the most commonly medical (mifepristone/misoprostol) and surgical abortion available to be included in the review. Duration of bleeding was longer in the medical abortion groups compared to vacuum aspiration. There was only one major complication (uterine perforation) in one trial in the surgical group. There was no difference between the groups for ongoing pregnancies at the time of follow-up or pelvic infections. No data on acceptability, side effects or women's satisfaction with the procedure were availbale for inclusion in the review. The results are derived from relatively small trials. Prostaglandins used alone seems to be less effective and more painful compared to surgical first-trimester abortion. However, there is inadequate evidence to comment on the acceptability and side effects of medical compared to surgical first-trimester abortions. There is a need for trials to address the efficacy of currently used methods and women's preferences more reliably.

The review of trials found that medical methods for abortion in early pregnancy can be safe and effective, with the most evidence of effectiveness for a combination of mifepristone and misoprostol (a prostaglandin). Almost all of the trials were done in well-resourced hospitals where women returned for check-up.

10.1002/14651858.CD003037.pub2

cochrane-simplification-train-3525

cochrane-simplification-train-3525

Among 409 retrieved references, we identified 16 RCTs; six of them, published between 1987 and 2007, met the selection criteria and were included in this review. Five hundred and forty RR patients and 1049 PMS contributed to the analysis. In RR MS, a decrease in the mean EDSS score (-0.33 and -0.45), was found respectively at 2 years and 35 months without any significant effect on sustained disease progression. The reduction of mean number of relapse was evident at 1 year (-0.35 ) 2 years (-0.51 ) and 35 months (-0.64), but significant studies ' heterogeneity was found. The number of hospitalisations and steroid courses were significantly reduced. No benefit was shown in P MS patients. No major toxicity was found. The most common systemic adverse event was a transient and self-limiting patterned reaction of flushing, chest tightness, sweating, palpitations, anxiety. Local injection-site reactions were observed in up to a half of patients treated with glatiramer acetate, thus making a blind assessment of outcomes questionable. Glatiramer acetate did show a partial efficacy in RR MS in term of relapse -related clinical outcomes, without any significant effect on clinical progression of disease measured as sustained disability. The drug is not effective in progressive MS patients.

Previous studies indicate that glatiramer acetate, a synthetic drug, is effective in animal models of MS, and shows some benefits in MS patients. The objective of this review was to assess the efficacy of glatiramer acetate in RRMS and PMS patients. Among the pertinent medical literature six studies met the criteria of the methodological quality necessary for their inclusion in this review. 540 RRMS patients and 1049 PMS patients contributed to this analysis. The data showed no beneficial effects on disease progression in both MS forms, a slight beneficial effect  in the reduction of risk of relapses in RRMS patients and no benefits in PMS patients. Adverse events such as flushing, chest tightness, sweating, palpitations, anxiety and  local injection-site reactions occurred quite frequently, but no major adverse effects were observed.

10.1002/14651858.CD004678.pub2

cochrane-simplification-train-3526

cochrane-simplification-train-3526

The 2005 update includes a new trial (Kuriyama 2002) to bring the total of included studies to three (total n=33). One study, which used a cross-over design (Tolbert 1993) provided insufficient data to conduct an analysis. Another crossover study (Findling 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity. The latest study (Kuriyama 2002) was motivated by evidence from epilepsy research and was focussed on a subgroup of children with pervasive developmental disorders (PDDs) who exhibited clinical features similar to those with pyroxidine-dependent epilepsy. This small study (n=8) only measured IQ and 'Social Quotient' and found a statistically significant benefit for IQ (5.2, 95% CI = [0.2 to 10.3]) when in the treated group, by using change scores. Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.

Studies investigating the effect of vitamin B6 in improving the behaviour of children with autism spectrum disorder have been reported for over three decades. The purpose of this review was to summarize those studies and analyse the effectiveness of vitamin B6 as an intervention. Only three studies met the inclusion criteria of this review and of these only one study reported adequate data for analysis. Results were inconclusive and sample sizes were small. Therefore the use of vitamin B6 for improving the behaviour of individuals with autism cannot currently be supported. Further research using larger, well-designed trials is needed.

10.1002/14651858.CD003497.pub2

cochrane-simplification-train-3527

cochrane-simplification-train-3527

This review detected 36 eligible randomized controlled trials involving four major groups of developmental care interventions, 19 sub-groups and multiple clinical outcomes. In addition, the long-term outcomes of a previously included trial were added to the review. The results of the review indicate that developmental care interventions demonstrate limited benefit to preterm infants with respect to: decreased moderate-severe chronic lung disease, decreased incidence of necrotizing enterocolitis and improved family outcome. Conversely, an increase in mild lung disease and an increase in the length of stay were demonstrated in infants receiving developmental care compared to controls. There is also very limited evidence of the long-term positive effect of NIDCAP on behavior and movement at 5 years corrected age but no effect on cognition. Other individualized developmental care interventions have also demonstrated some effect in enhancing neurodevelopmental outcome. Although a limited number of other benefits were demonstrated, those results were from single studies with small sample sizes. The lack of blinding of the assessors was a significant methodological flaw in half of the studies. The cost of the interventions and personnel was not considered in any of the studies. Because of the inclusion of multiple interventions in most studies, the determination of the effect of any single intervention is difficult. Although there is evidence of limited benefit of developmental care interventions overall, and no major harmful effects reported, there were a large number of outcomes for which no or conflicting effects were demonstrated. The single trials that did show a significant effect of an intervention on a major clinical outcome were based on small sample sizes, and the findings were often not supported in other small trials. Before a clear direction for practice can be supported, evidence demonstrating more consistent effects of developmental care interventions on important short- and long-term clinical outcomes is needed. The economic impact of the implementation and maintenance of developmental care practices should be considered by individual institutions.

The review of trials suggests that these interventions may have some benefit to the outcomes of preterm infants; however, there continues to be conflicting evidence among the multiple studies. Before a clear direction for practice can be supported, evidence demonstrating more consistent effects of developmental care interventions on important short- and long-term clinical outcomes is needed. The economic impact of the implementation and maintenance of developmental care practices should be considered by individual institutions.

10.1002/14651858.CD001814.pub2

cochrane-simplification-train-3528

cochrane-simplification-train-3528

This review includes 19 studies with a total of 14,890 participants. We categorised the included studies according to the modes used to deliver the recruitment strategy: head to head comparison of individual recruitment strategies; comparison of the same delivery mode but with different content or intensity; and the addition of another mode to an existing recruitment method. We identified three studies that made head-to-head comparisons of different types of recruitment strategies. Of these, only one study detected a significant effect, finding that a personal phone call was more effective than a generic invitation letter (RR 40.73, 95% CI 2.53 to 654.74). Five studies compared interventions using the same delivery modes but different content. Results showed that tailored messages through an interactive voice response system resulted in a higher recruitment rate than assessment of smoking status alone using the same system (RR 8.64, 95% CI 4.41 to 16.93), and that text messages indicating scarcity of places available were more effective than generic text message reminders (RR 1.45, 95% CI 1.07 to 1.96). One study compared interventions using the same delivery mode but different intensity and found that allowing for more phone call attempts to reach potential participants can result in better recruitment (RR 1.87, 95% CI 1.61 to 2.18). Finally, 10 studies investigated the effect of adding a recruitment mode to existing recruitment strategies. Findings showed that: adding a text message reminder or real quotes from participants to a personal phone call improved recruitment of participants (RR 3.38, 95% CI 1.26 to 9.08 and RR 29.07, 95% CI 1.74 to 485.70, respectively); that adding a personal phone call to an existing newsletter can also increase recruitment rates (RR 65.12, 95% CI 4.06 to 1045.4]); that a reactive-proactive recruitment phase is more effective than a proactive phase alone (63.8% versus 47.5%, RR not available); and that active recruitment at schools is more effective than passive recruitment (p < 0.001, denominator not available for calculation of RR). Additionally, a number of studies in this category showed that providing incentives can effectively increase the number of participants recruited into smoking cessation programmes. Out of the 19 included studies, only four reported on the effect of recruitment strategy on smoking cessation at six months or longer. Three of these studies compared strategies that used the same delivery mode with different content. Their results were non-significant. The remaining three studies evaluated adding an additional mode to an existing recruitment intervention. Only one of them showed a significant difference in the levels of smoking cessation that favoured the enhanced recruitment strategy, but this may have reflected the offer of incentives once in the programme rather than the recruitment strategy itself (RR at 15 or 18 months 2.60, 95% CI 1.48 to 4.56). The substantial heterogeneity across the included studies restricts our ability to draw firm conclusions about the effectiveness of different recruitment strategies in relation to recruitment of participants into smoking cessation programmes or levels of smoking cessation. The limited evidence, however, suggests that the following elements may improve the recruitment of smokers into cessation programmes: personal, tailored interventions; recruitment methods that are proactive in nature; and more intensive recruitment strategies (i.e., those strategies that require increased contact with potential participants).

This review aims to identify whether certain recruitment strategies can help to increase the number of smokers enrolling into quit services. It also aims to determine whether these recruitment strategies have any impact on people successfully quitting smoking at six months or longer. This review covers 19 studies, with almost 15,000 participants, but the significant differences across these studies meant that we were unable to draw conclusive answers to our research questions. Our findings do, however, suggest that the following elements could result more people joining quit smoking programmes: (1) recruitment strategies tailored to the individual; (2) proactive strategies; and (3) increased contact time with potential participants. This review also highlights the areas within this field that need more attention: identifying the elements of a recruitment strategy that are more likely to effectively engage smokers; whether or not elements of recruitment strategies have an impact on quit rates; and identifying those recruitment strategies (or different combinations of particular recruitment strategies with certain smoking cessation programmes) that work better for different population groups.

10.1002/14651858.CD009187.pub2

cochrane-simplification-train-3529

cochrane-simplification-train-3529

We included five studies with a total of 311 eyes (247 participants) of which 133 eyes (participants) were quasi-randomised. One hundred and sixty eyes which had trabeculectomy were compared to 151 eyes that had non-penetrating glaucoma surgery (of which 101 eyes had deep sclerectomy and 50 eyes had viscocanalostomy). The confidence interval (CI) for the odds ratio (OR) of success (defined as achieving target eye pressure without eye drops) does not exclude a beneficial effect of either deep sclerectomy or trabeculectomy (OR 0.98, 95% CI 0.51 to 1.88). The odds of success in viscocanalostomy participants was lower than in trabeculectomy participants (OR 0.33, 95% CI 0.13 to 0.81). We did not combine the different types of non-penetrating surgery because there was evidence of a subgroup difference when examining total success. The odds ratio for achieving target eye pressure with or without eye drops was imprecise and was compatible with a beneficial effect of either trabeculectomy or non-penetrating filtration surgery (NPFS) (OR 0.79, 95% CI 0.35 to 1.79). Operative adjuvants were used in both treatment groups; more commonly in the NPFS group compared to the trabeculectomy group but no clear effect of their use could be determined. Although the studies were too small to provide definitive evidence regarding the relative safety of the surgical procedures we noted that there were relatively fewer complications with non-filtering surgery compared to trabeculectomy (17% and 65% respectively). Cataract was more commonly reported in the trabeculectomy studies. None of the five trials used quality of life measure questionnaires. The methodological quality of the studies was not good. Most studies were at high risk of bias in at least one domain and for many, there was lack of certainty due to incomplete reporting. Adequate sequence generation was noted only in one study. Similarly, only two studies avoided detection bias. We detected incomplete outcome data in three of the included studies. This review provides some limited evidence that control of IOP is better with trabeculectomy than viscocanalostomy. For deep sclerectomy, we cannot draw any useful conclusions. This may reflect surgical difficulties in performing non-penetrating procedures and the need for surgical experience. This review has highlighted the lack of use of quality of life outcomes and the need for higher methodological quality RCTs to address these issues. Since it is unlikely that better IOP control will be offered by NPFS, but that these techniques offer potential gains for patients in terms of quality of life, we feel that such a trial is likely to be of a non-inferiority design with quality of life measures.

This review included five trials with 311 eyes (267 participants). These studies included 160 eyes which had trabeculectomy compared to 151 eyes that had non-penetrating glaucoma surgery, of which 101 eyes had deep sclerectomy and 50 eyes had viscocanalostomy. This review showed that trabeculectomy is better in terms of achieving total success (pressure controlled without eyedrops) than non-penetrating filtering procedures. Although when we looked at the outcome of partial success (pressure controlled with additional eyedrops) it was more imprecise and our results could not exclude one surgical approach being better than the other. However, the review noted that these studies had some limitations regarding their design and were too small to give definitive information on differences in complications following surgery. None of the studies measured quality of life.

10.1002/14651858.CD007059.pub2

cochrane-simplification-train-3530

cochrane-simplification-train-3530

A total of 171 studies were included in the analysis (24,868 participants). The included studies were undertaken between 1984 and 2012. Studies had homogenous characteristics in terms of design, intervention and outcome measures. The assessment of quality with the risk of bias tool revealed that the great majority of them failed to report methodological details, like the method of random sequence generation, the allocation concealment and blinding. Moreover, most of the included studies were sponsored by drug companies, so the potential for overestimation of treatment effect due to sponsorship bias should be considered in interpreting the results. Fluoxetine was as effective as the TCAs when considered as a group both on a dichotomous outcome (reduction of at least 50% on the Hamilton Depression Scale) (OR 0.97, 95% CI 0.77 to 1.22, 24 RCTs, 2124 participants) and a continuous outcome (mean scores at the end of the trial or change score on depression measures) (SMD 0.03, 95% CI -0.07 to 0.14, 50 RCTs, 3393 participants). On a dichotomous outcome, fluoxetine was less effective than dothiepin or dosulepin (OR 2.13, 95% CI 1.08 to 4.20; number needed to treat (NNT) = 6, 95% CI 3 to 50, 2 RCTs, 144 participants), sertraline (OR 1.37, 95% CI 1.08 to 1.74; NNT = 13, 95% CI 7 to 58, 6 RCTs, 1188 participants), mirtazapine (OR 1.46, 95% CI 1.04 to 2.04; NNT = 12, 95% CI 6 to 134, 4 RCTs, 600 participants) and venlafaxine (OR 1.29, 95% CI 1.10 to 1.51; NNT = 11, 95% CI 8 to 16, 12 RCTs, 3387 participants). On a continuous outcome, fluoxetine was more effective than ABT-200 (SMD -1.85, 95% CI -2.25 to -1.45, 1 RCT, 141 participants) and milnacipran (SMD -0.36, 95% CI -0.63 to -0.08, 2 RCTs, 213 participants); conversely, it was less effective than venlafaxine (SMD 0.10, 95% CI 0 to 0.19, 13 RCTs, 3097 participants). Fluoxetine was better tolerated than TCAs considered as a group (total dropout OR 0.79, 95% CI 0.65 to 0.96; NNT = 20, 95% CI 13 to 48, 49 RCTs, 4194 participants) and was better tolerated in comparison with individual ADs, in particular amitriptyline (total dropout OR 0.62, 95% CI 0.46 to 0.85; NNT = 13, 95% CI 8 to 39, 18 RCTs, 1089 participants), and among the newer ADs ABT-200 (total dropout OR 0.18, 95% CI 0.08 to 0.39; NNT = 3, 95% CI 2 to 5, 1 RCT, 144 participants), pramipexole (total dropout OR 0.12, 95% CI 0.03 to 0.42, NNT = 3, 95% CI 2 to 5, 1 RCT, 105 participants), and reboxetine (total dropout OR 0.60, 95% CI 0.44 to 0.82, NNT = 9, 95% CI 6 to 24, 4 RCTs, 764 participants). The present study detected differences in terms of efficacy and tolerability between fluoxetine and certain ADs, but the clinical meaning of these differences is uncertain. Moreover, the assessment of quality with the risk of bias tool showed that the great majority of included studies failed to report details on methodological procedures. Of consequence, no definitive implications can be drawn from the studies' results. The better efficacy profile of sertraline and venlafaxine (and possibly other ADs) over fluoxetine may be clinically meaningful, as already suggested by other systematic reviews. In addition to efficacy data, treatment decisions should also be based on considerations of drug toxicity, patient acceptability and cost.

In May 2012 we searched, in a wide-ranging way, for all the useful studies (randomised controlled trials, or RCTs) we could find which compared fluoxetine with any other antidepressant in treating people with depression. One hundred and seventy-one RCTs were included, with 24,868 people in the analyses. Combining the results from all the trials, fluoxetine was similarly effective, but better tolerated, than older generation (tricyclic) antidepressants. In comparison with other new generation antidepressants, important differences in efficacy and in tolerability were found between fluoxetine and some of the antidepressants, for example, fluoxetine was less effective than sertraline and mirtazapine but better tolerated than reboxetine. These differences might have a clinical impact in everyday practice. However, when interpreting these differences it is important to bear in mind that the studies were short in duration (eight weeks or less) and that the average size of each trial was small (each included around 100 people). Moreover, most of the included studies were sponsored by drug companies, which could potentially have led to an overestimation of treatment effect. As a consequence, it is difficult to draw clear, clinically meaningful conclusions. More reliable information is needed about the respective safety profiles of antidepressants.

10.1002/14651858.CD004185.pub3

cochrane-simplification-train-3531

cochrane-simplification-train-3531

We included a total of 15 eligible studies randomising 3760 participants in this review. The age of participants across the studies ranged from 3 to 101 years, with a mean of 25.42 years. 48% of participants were male. All included studies were published between 2002 and 2016. Two of the 15 studies declared that the financial support was from companies that manufacture restorative material. Five studies were individually randomised parallel-group studies; six were cluster-randomised parallel-group studies; and four were randomised studies that used a split-mouth design. Eleven studies evaluated the effects of ART on primary teeth only, and four on permanent teeth. The follow-up period of the included studies ranged from 6 months to 36 months. We judged all studies to be at high risk of bias. For the main comparison of ART compared to conventional treatment using the same material: all but two studies used high-viscosity glass ionomer (H-GIC) as the restorative material; one study used a composite material; and one study used resin-modified glass ionomer cement (RM-GIC)). Compared to conventional treatment using H-GIC, ART may increase the risk of restoration failure in the primary dentition, over a follow-up period from 12 to 24 months (OR 1.60, 95% CI 1.13 to 2.27, five studies; 643 participants analysed; low-quality evidence). Our confidence in this effect estimate is limited due to serious concerns over risk of performance and attrition bias. For this comparison, ART may reduce pain during procedure compared with conventional treatment (MD -0.65, 95% CI -1.38 to 0.07; 40 participants analysed; low-quality evidence) Comparisons of ART to conventional treatment using composite or RM-GIC were downgraded to very low quality due to indirectness, imprecision and high risk of performance and attrition bias. Given the very low quality of the evidence from single studies, we are uncertain about the restoration failure of ART compared with conventional treatment using composite over a 24-month follow-up period (OR 1.11, 95% CI 0.54 to 2.29; one study; 57 participants) and ART using RM-GIC in the permanent teeth of older adults with root caries lesions over a six-month follow-up period (OR 2.71, 95% CI 0.94 to 7.81; one study; 64 participants). No studies reported on adverse events or costs. Low-quality evidence suggests that ART using H-GIC may have a higher risk of restoration failure than conventional treatment for caries lesions in primary teeth. The effects of ART using composite and RM-GIC are uncertain due to the very low quality of the evidence and we cannot rely on the findings. Most studies evaluated the effects of ART on the primary dentition. Well-designed RCTs are required that report on restoration failure at clinically meaningful time points, as well as participant-reported outcomes such as pain and discomfort. Due to the potential confounding effects from the use of different dental materials, a robust body of evidence on the effects of ART compared with conventional treatment using the same restoration material is necessary. We identified four ongoing trials that could provide further insights into this area.

This review searched the available evidence that was up to date at 22 February 2017. We found 15 relevant studies including 3760 participants with an average age of 25 years (range 3 to 101) where 48% were male. The follow-up period in the trials ranged from 6 to 36 months. Two of the 15 studies declared financial support from companies that made tooth-filling material. In addition, we found four ongoing studies. There is low-quality evidence to suggest that primary teeth treated with the ART approach using high viscosity glass ionomer cement may be more likely than those receiving conventional treatment with the same material to result in restoration failure. In the treatment of primary teeth, ART may reduce pain experience compared with conventional treatment. The evidence available for evaluating the differences between ART and conventional treatments using other restorative materials or in permanent teeth is very low quality so we cannot draw any conclusions. None of the included studies reported on negative side effects or costs. The available evidence is low- to very low-quality. It is likely that further high-quality research may change our findings. There are four ongoing studies that may provide more information in the future.

10.1002/14651858.CD008072.pub2

cochrane-simplification-train-3532

cochrane-simplification-train-3532

We included 25 RCTs that evaluated the BP lowering effects of seven nonselective beta-blockers in 1264 people with hypertension. Among the 25 RCTs, four were parallel studies and 21 were cross-over studies. Overall, nonselective beta-blockers lowered systolic BP and diastolic BP compared with placebo. Nonselective beta-blockers, in the recommended dose range, did not showed a convincing dose-response relationship by direct comparison. The once (1x) and twice (2x) starting dose subgroups contained the largest sample size. The estimate of BP lowering efficacy for nonselective beta-blockers by combining the 1x and 2x starting dose subgroup was -10 mmHg (95% CI -11 to -8) for systolic BP and -7 mmHg (95% CI -8 to -6) for diastolic BP (low-quality evidence). Nonselective beta-blockers starting at the 1x recommended starting doses lowered heart rate by 12 beats per minute (95% CI 10 to 13) (low-quality evidence). The dose-response relationship in heart rate was evident by both direct and indirect comparison. Due to imprecision, there was no clear evidence of an effect of nonselective beta-blockers on pulse pressure in any dose subgroups except for a small reduction with the 2x starting dose (-2.2 mmHg, 95% CI -3.7 to -0.7) (very low quality evidence). The point estimates in the 1x, four times (4x) and eight times (8x) starting dose subgroups were similar to the 2x starting dose subgroup. Therefore, it would appear that if nonselective beta-blockers do lower pulse pressure, the magnitude is likely to be about 2 mmHg. There were very limited data (two studies) on withdrawals due to adverse effects (risk ratio (RR) 0.84; 95% CI 0.38 to 1.82). In people with mild-to-moderate hypertension, nonselective beta-blockers lowered peak BP by a mean of -10/-7 mmHg (systolic/diastolic) and reduced heart rate by 12 beats per minute. Propranolol and penbutolol were the two drugs that contributed to most of the data for nonselective beta-blockers. This estimate is likely exaggerated due to the presence of extreme outliers and other sources of bias. If we removed the extreme outliers from the analysis, the estimate for non-selective beta-blockers was lower (-8/-5 mmHg (systolic/diastolic)). Nonselective beta-blockers did not show a convincing graded dose-response in the recommended dose range for systolic BP and diastolic BP, while higher dose nonselective beta-blockers provided greater reduction of heart rate. Using higher dose nonselective beta-blockers might cause more side effects, such as bradycardia, without producing an additional BP lowering effect. The effect of nonselective beta-blockers on pulse pressure was likely small, at about 2 mmHg.

We developed a comprehensive search strategy of all relevant scientific databases to identify all clinical trials to answer this question. Participants had to have a baseline systolic blood pressure (the top number of a blood pressure reading) of at least 140 mmHg or a diastolic blood pressure (the bottom number of a blood pressure reading) of at least 90 mmHg, or both of these. We did not restrict participants by age, gender, baseline risk or any other medical conditions. We found 25 clinical trials that compared the blood pressure lowering effect of seven nonselective beta-blockers with placebo in 1264 people with high blood pressure. On average, nonselective beta-blockers lowered blood pressure by about 10 mmHg systolic and 7 mmHg diastolic, and reduced heart rate by 12 beats per minute. This estimate is likely greater than the true effect because of biases in the running and reporting of the trials. We did not find convincing evidence that higher doses of nonselective beta-blockers lowered blood pressure more than lower doses. However, higher doses of nonselective beta-blockers significantly lowered heart rate compared with lower doses, which could lead to more side effects. Since the blood pressure lowering effect for systolic is similar to the blood pressure lowering effect of diastolic, the effect of this subclass on pulse pressure (the difference between systolic and diastolic) was small at about 2 mmHg. The quality of the evidence is low due to the presence of extreme outliers and high risk of biases.

10.1002/14651858.CD007452.pub2

cochrane-simplification-train-3533

cochrane-simplification-train-3533

We identified seven trials, with 895 evaluable participants for this review. All provided data suitable for the primary outcome meta-analysis. One of the trials was new since the last version of this Cochrane systematic review. Risk of bias in the older, smaller studies included some unclear- or high-risk assessments, whereas we deemed the larger studies at low risk of bias. Overall, 79/452 (17%) participants allocated to corticosteroids had incomplete recovery of facial motor function six months or more after randomisation; significantly fewer than the 125/447 (28%) in the control group (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.50 to 0.80, seven trials, n = 895). The number of people who need to be treated with corticosteroids to avoid one incomplete recovery was 10 (95% CI 6 to 20). The reduction in the proportion of participants with cosmetically disabling sequelae six months after randomisation was very similar in the corticosteroid and placebo groups (RR 0.96, 95% CI 0.40 to 2.29, two trials, n = 75, low-quality evidence). However, there was a significant reduction in motor synkinesis during follow-up in participants receiving corticosteroids (RR 0.64, 95% CI 0.45 to 0.91, three trials, n = 485, moderate-quality evidence). Three studies explicitly recorded the absence of adverse effects attributable to corticosteroids. One trial reported that three participants receiving prednisolone had temporary sleep disturbances and two trials gave a detailed account of adverse effects occurring in 93 participants, all non-serious; the combined analysis of data from these three trials found no significant difference in adverse effect rates between people receiving corticosteroids and people receiving placebo (RR 1.04, 95% CI 0.71 to 1.51, n = 715). The available moderate- to high-quality evidence from randomised controlled trials showed significant benefit from treating Bell's palsy with corticosteroids.

We identified seven clinical trials involving 895 people with one-sided mild, moderate or severe Bell's palsy of unknown cause. All of these trials reported rates of incomplete recovery (the proportion of people left with facial weakness) and we were able to combine the results. People in the studies were aged from 2 to 84 years. They were treated with corticosteroids or placebo (inactive treatment), either alone or in combination with other therapies. One trial only involved children, from 24 months to 74 months old. The duration of the included studies for adults and children ranged from 157 days to 12 months. Incomplete recovery According to moderate quality to high quality evidence, corticosteroids reduced the number of people left with facial weakness after Bell's palsy compared to placebo (a pretend medicine). This finding was based on data from seven studies involving 895 participants with Bell's palsy of varying degrees of severity. We calculated that to stop one person from being left with facial weakness, 10 people need to be treated. Five studies provided data on long-term after-effects of Bell's palsy following treatment. Two of the studies (75 participants) looked at persistent effects on facial appearance after six months or more. The effect was nearly the same for corticosteroids and placebo, showing that participants who had corticosteroids benefited slightly, although this evidence was low quality. Data from three studies (485 participants) showed clearly that people who received corticosteroids developed less motor synkinesis (unwanted facial movements) and crocodile tears (watery eyes when eating or chewing), compared with people who received placebo alone. This finding was based on moderate-quality evidence. Side effects Three studies reported that no side effects could be attributed to corticosteroid treatment. Based on moderate-quality evidence from three studies (715 participants), numbers experiencing side effects were similar with corticosteroids and placebo. The evidence is current to March 2016.

10.1002/14651858.CD001942.pub5

cochrane-simplification-train-3534

cochrane-simplification-train-3534

Twelve trials met our eligibility criteria, included the three added in this update. The studies included a total of 4145 women. Eight trials were conducted in the USA; the others were from Australia, Nepal, Pakistan, and Syria. Four studies provided one session before hospital discharge; three had structured counseling of varying intensity and one involved informal counseling. Of eight interventions with than one contact, five focused on adolescents. Three of the five involved home visiting, one provided multiple clinic services, and one had in-person contact and phone follow-up. Of the remaining three for women of varying ages, two involved home visits and one provided phone follow-up. Our sensitivity analysis included six trials with evidence of moderate or high quality. In a study with adolescents, the group with home-based mentoring had fewer second births within two years compared to the control group (OR 0.41, 95% CI 0.17 to 1.00). The other five interventions had no effect. Of trials with lower quality evidence, two showed some effectiveness. In Nepal, women with an educational session immediately postpartum were more likely to use contraception at six months than those with a later or no session (OR 1.62, 95% CI 1.06 to 2.50). In an Australian study, teenagers in a structured home-visiting program were more likely to have effective contraception use at six months than those with standard home visits (OR 3.24; 95% CI 1.35 to 7.79). We focused our results summary on trials with moderate or high quality evidence. Overall, the overall quality of evidence in this review was moderate to low and the evidence of effectiveness was mostly low quality. The interventions could be improved by strengthening the program design and implementation. Some studies did not report program training for providers, adherence to the intervention protocol, or measurement of participants' knowledge and skills. Many trials did not have an objective outcome measure, i.e., pregnancy test or structured questionnaire for contraceptive use. Valid and reliable outcome measures are needed to obtain meaningful results. Still, given the associated costs and logistics, some programs would not be feasible in many settings.

Through June 2015, we searched for trials of education about family planning after having a baby. We also wrote to researchers to find other trials. The trials had to study how much the program affected family planning use. The program must have occurred within a month after the birth. We entered the data into RevMan and used the odds ratio to examine effect. We also looked at the quality of the research methods. We found 12 trials with 4145 women. Eight studies were from the USA and the others were from Australia, Nepal, Pakistan, and Syria. Four trials provided one counseling session before hospital discharge. Of eight studies with more than one contact, five focused on teens. Three of the five had home visiting, one used clinic services, and one had personal and phone contacts. Of three studies with women and teens, two had home visits and one used phone contact. Six trials had results of moderate quality. In a study with adolescents, the group with home-based mentoring had fewer second births within two years compared to the control group. Of trials with lower quality evidence, two showed some effect. In Nepal, more of the women with some counseling right after delivery may use birth control at six months than those with a session later or none. In Australia, more teens in a special home-visiting program used birth control correctly at six months than those with standard home visits. We found moderate to low quality results overall. Most of those with some effect were low quality. Better program design and carrying out could make them stronger. Even still, some programs might cost too much for some settings.

10.1002/14651858.CD001863.pub4

cochrane-simplification-train-3535

cochrane-simplification-train-3535

We include 15 randomised controlled trials (RCTs) (17 comparisons, ˜59,000 participants), which used a variety of interventions from providing all food to advice on how to reduce saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of cardiovascular events by 17% (risk ratio (RR) 0.83; 95% confidence interval (CI) 0.72 to 0.96, 13 comparisons, 53,300 participants of whom 8% had a cardiovascular event, I² 65%, GRADE moderate quality of evidence), but effects on all-cause mortality (RR 0.97; 95% CI 0.90 to 1.05; 12 trials, 55,858 participants) and cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 12 trials, 53,421 participants) were less clear (both GRADE moderate quality of evidence). There was some evidence that reducing saturated fats reduced the risk of myocardial infarction (fatal and non-fatal, RR 0.90; 95% CI 0.80 to 1.01; 11 trials, 53,167 participants), but evidence for non-fatal myocardial infarction (RR 0.95; 95% CI 0.80 to 1.13; 9 trials, 52,834 participants) was unclear and there were no clear effects on stroke (any stroke, RR 1.00; 95% CI 0.89 to 1.12; 8 trials, 50,952 participants). These relationships did not alter with sensitivity analysis. Subgrouping suggested that the reduction in cardiovascular events was seen in studies that primarily replaced saturated fat calories with polyunsaturated fat, and no effects were seen in studies replacing saturated fat with carbohydrate or protein, but effects in studies replacing with monounsaturated fats were unclear (as we located only one small trial). Subgrouping and meta-regression suggested that the degree of reduction in cardiovascular events was related to the degree of reduction of serum total cholesterol, and there were suggestions of greater protection with greater saturated fat reduction or greater increase in polyunsaturated and monounsaturated fats. There was no evidence of harmful effects of reducing saturated fat intakes on cancer mortality, cancer diagnoses or blood pressure, while there was some evidence of improvements in weight and BMI. The findings of this updated review are suggestive of a small but potentially important reduction in cardiovascular risk on reduction of saturated fat intake. Replacing the energy from saturated fat with polyunsaturated fat appears to be a useful strategy, and replacement with carbohydrate appears less useful, but effects of replacement with monounsaturated fat were unclear due to inclusion of only one small trial. This effect did not appear to alter by study duration, sex or baseline level of cardiovascular risk. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturated fats. The ideal type of unsaturated fat is unclear.

We assessed the effect of cutting down the amount of saturated fat we eat on health outcomes including dying, heart disease, stroke and cancer for at least two years. We only looked at studies of adults (18 years or older). This included men and women with and without cardiovascular disease. We did not include studies of acutely ill people or pregnant or breastfeeding women. We found 15 studies with over 59,000 participants. The evidence is current to March 2014. The review found that cutting down on saturated fat led to a 17% reduction in the risk of cardiovascular disease (including heart disease and strokes), but no effects on the risk of dying. The review found no clear health benefits of replacing saturated fats with starchy foods or protein. Changing the type of fat we eat, replacing saturated fats with polyunsaturated fats, seems to protect us better, reducing our risk of heart and vascular problems. The greater the decrease in saturated fat, and the more serum total cholesterol is reduced, the greater the protection. People who are currently healthy appear to benefit as much as those at increased risk of heart disease or stroke (people with high blood pressure, high serum cholesterol or diabetes, for example), and people who have already had heart disease or stroke. There was no clear difference in effect between men and women. There is a large body of evidence, including almost 60,000 people who have been in studies assessing effects of reducing saturated fat for at least two years each. Together the studies provide moderate-quality evidence that reducing saturated fat and replacing it with polyunsaturated fats reduces our risk of cardiovascular disease.

10.1002/14651858.CD011737

cochrane-simplification-train-3536

cochrane-simplification-train-3536

Eight studies with 343 participants were included. The review found evidence for lower post-treatment OCD severity and reduced risk of continuing with OCD for the BT/CBT group compared to pill placebo or wait-list comparisons. There was no evidence found that the efficacy of BT/CBT alone and medication alone differ in terms of post treatment symptom severity or in the risk of having OCD. There was some evidence of a benefit for combined BT/CBT and medication compared to medication alone but not relative to BT/CBT alone. The low rates of drop out suggested BT/CBT is an acceptable treatment to child and adolescent patients and their families. Although only based on a small number of studies which vary in quality, behavioural or cognitive-behaviour therapy alone appears to be an effective treatment for OCD in children and adolescents. It is as effective as medication alone and may lead to better outcomes when combined with medication compared to medication alone. Additional higher quality trials are needed to confirm these findings.

This review identified eight randomised controlled trials involving 343 participants, evaluating the benefits of behavioural and cognitive-behavioural therapy. The results show that, compared to a wait-list or pill placebo, BT/CBT is an effective treatment for reducing OCD symptoms and lowering the risk of having OCD after treatment. Based on three studies that directly compared BT/CBT with medication, there was no current evidence to suggest that either BT/CBT or medication was superior to the other. When combined with medication, BT/CBT produces better outcomes than medication alone. Although based on a small number of studies, these findings provide support for the value of BT/CBT in the treatment of children and adolescents with OCD.

10.1002/14651858.CD004856.pub2

cochrane-simplification-train-3537

cochrane-simplification-train-3537

We identified only one randomised controlled trial, which compared open surgery and radiotherapy in 234 patients with early glottic laryngeal cancer. The overall risk of bias in this study was high. For T1 tumours, the five-year survival was 91.7% following radiotherapy and 100% following surgery and for T2 tumours, 88.8% following radiotherapy and 97.4% following surgery. There were no significant differences in survival between the two groups. For T1 tumours, the five-year disease-free survival rate was 71.1% following radiotherapy and 100.0% following surgery, and for the T2 tumours, 60.1% following radiotherapy and 78.7% following surgery. Only the latter comparison was statistically significant (P value = 0.036), but statistical significance would not have been achieved with a two-sided test. Data were not available on side effects, quality of life, voice outcomes or cost. We identified no randomised controlled trials that included endolaryngeal surgery. A number of trials comparing endolaryngeal resection and radiotherapy have terminated early because of difficulty recruiting participants. One randomised controlled trial is still ongoing. There is only one randomised controlled trial comparing open surgery and radiotherapy but its interpretation is limited because of concerns about the adequacy of treatment regimens and deficiencies in the reporting of the study design and analysis.

This review of trials identified just one trial including 234 patients with early glottic cancer, which compared radiotherapy to open surgery. This was a multicentre randomised controlled trial undertaken in the former Soviet Union, Hungary and Czechoslovakia. Patients were followed up for five years and recurrence-free and survival rates were measured. The results of this trial showed that there was no significant difference in survival between patients treated with radiotherapy or open surgery. Further data from trials comparing radiotherapy and endolaryngeal surgery are needed to determine the best way of treating early laryngeal cancer, however a number of studies have been abandoned because of difficulties in recruiting participants. One trial is still ongoing. We found that there is not enough evidence to show which form of treatment might be better for people with early-stage larynx cancer. The included study is of low quality. The evidence in this review is up to date to September 2014.

10.1002/14651858.CD002027.pub2

cochrane-simplification-train-3538

cochrane-simplification-train-3538

Ten studies were found including 366 patients in total. We included eight studies in the as-published data analysis, comprising 337 patients . The methodological quality of the studies was overall satisfactory, however there was potential for introduction of significant bias in several specific areas relating to performance of the index test and to the timing of index versus reference tests. Results demonstrated a sensitivity estimate of 0.84 (95% confidence interval (CI) 0.69 to 0.93). The 95% approximate prediction interval was very wide (0.34 to 0.98). Data in three studies were available as a four-vessel interpretation model and the data could be re-analysed to a four-vessel interpretation model in a further five studies, comprising 314 patient events. Results demonstrated a similar sensitivity estimate of 0.85 (95% CI 0.77 to 0.91) but with an improved 95% approximate prediction interval (0.56 to 0.96). The available evidence cannot support the use of CT angiography as a mandatory test, or as a complete replacement for neurological testing, in the management pathway of patients who are suspected to be clinically brain dead. CT angiography may be useful as a confirmatory or add-on test following a clinical diagnosis of death, assuming that clinicians are aware of the relatively low overall sensitivity. Consensus on a standard radiological interpretation protocol for future published studies would facilitate further meta-analysis.

Ten studies were found, including 366 patients in total. Most of the studies were performed in intensive care departments but involved only small numbers of patients. In most studies it would be possible for the doctors performing the CTA test to already know the results of the clinical test. This might affect the study results, however this situation would also be the case in normal medical practice. Methods used to report the CTA study also varied from study to study and so the published results were re-analysed to take this into account. When compared to clinical testing for brain death, the CTA test had a sensitivity of 0.85. This means that in 100 cases of patients satisfying the clinical tests for death, the CTA test will correctly identify 85 of the cases. The data also showed that this might be as few as 77 cases per 100 and as many as 91 cases per 100. Our review was unable to tell us how many patients the CTA might falsely give a diagnosis of death for, when the patient was not dead. Based on these results, it appears that CTA is not good enough to be a compulsory test.

10.1002/14651858.CD009694.pub2

cochrane-simplification-train-3539

cochrane-simplification-train-3539

We identified no new studies for this update. We included five trials with a total of 1292 participants; agents used for thrombolysis were recombinant tissue plasminogen activator and urokinase. Trials were generally of moderate methodological quality. The quality of evidence according to GRADE was generally low owing to risk of bias (lack of blinding), imprecision in estimates, and heterogeneity. Trial results showed no clear differences in limb salvage, amputation, or death at 30 days (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.41 to 2.55, 4 studies, 636 participants; OR 0.97, 95% CI 0.51 to 1.85, 3 studies, 616 participants; OR 0.59, 95% CI 0.31 to 1.14, 4 studies, 636 participants, respectively), and we rated the evidence as low, low, and moderate quality, respectively. Trial results show no clear differences for any of the three outcomes at six months or one year between initial surgery and initial thrombolysis. A single study evaluated vessel patency, so no overall association could be determined (OR 0.46, 95% CI 0.08 to 2.76, 20 participants; very low-quality evidence). Evidence of increased risk of major haemorrhage (OR 3.22, 95% CI 1.79 to 5.78, 4 studies, 1070 participants; low-quality evidence) and distal embolisation (OR 31.68, 95% CI 6.23 to 161.07, 3 studies, 678 participants; very low-quality evidence) was associated with thrombolysis treatment at 30 days, and there was no clear difference in stroke (OR 5.33, 95% CI 0.95 to 30.11, 5 studies, 1180 participants; low-quality evidence). Participants treated by initial thrombolysis had a greater reduction in the level of intervention required, compared with a pre-intervention prediction, at 30 days (OR 9.06, 95% CI 4.95 to 16.56, 2 studies, 502 participants). None of the included studies evaluated time to thrombolysis as an outcome. There is currently no evidence in favour of either initial thrombolysis or initial surgery as the preferred option in terms of limb salvage, amputation, or death at 30 days, six months, or one year. Low-quality evidence suggests that thrombolysis may be associated with higher risk of haemorrhagic complications and ongoing limb ischaemia (distal embolisation). The higher risk of complications must be balanced against risks of surgery in each individual case. Trial results show no statistical difference in stroke, but the confidence interval is very wide, making it difficult to interpret whether this finding is clinically important. We used GRADE criteria to assess the quality of the evidence as generally low. We downgraded quality owing to risk of bias, imprecision, and heterogeneity between included studies.

Authors of the review identified five controlled trials with a total of 1292 participants who needed immediate care for reduced blood flow in the leg(s) (current until 7 May 2018). Participants were randomly assigned to one of two groups for initial treatment: (1) non-surgical thrombolysis, or (2) surgery. The specific agents used to break up clots (thrombolytic agents) were called recombinant tissue plasminogen activator and urokinase. The included studies provided no clear evidence about which treatment - thrombolysis or surgery - was a better option for preventing limb amputation (limb salvage) and no clear evidence about which treatment was better for preventing death or improving amputation rates within one month, six months, or one year after initial treatment. Evidence for these three outcomes at one month was rated between low and very low quality. No conclusion can be made about which treatment was better for keeping vessels unblocked after treatment (vessel patency) because this outcome was not well reported. More major complications, including bleeding (haemorrhage) and continued ischaemia or blockage (distal embolisation), were reported in the group receiving thrombolysis. There was no difference in the occurrence of stroke at one month between the two treatment groups. Although people receiving initial thrombolysis had increased risk of some complications, they showed greater reduction in the level of intervention required compared with that predicted before intervention. The higher risks of complications with thrombolysis have to be weighted against individual risks in surgery. The quality of the evidence was generally low. We downgraded the quality owing to risk of bias. Bias is a way to describe how researchers, clinicians, or participants might influence results unintentionally. Blinding is a method used to prevent people involved in the trial from knowing what treatment group a participant was in and reducing measurement bias. None of the studies included in this review used methods to stop participants or researchers or outcome assessors from knowing what treatment they were assigned to. Also, there was uncertainty about the true effect of each treatment type. Results show wide differences in outcome measures (effects) between studies (heterogeneity). For example, following surgical treatment, one-year mortality ranged from 9.8% to 42%. Such a wide range in percentages may indicate that the studies compared were quite different. In addition, both selection criteria (duration of treatment and severity of ischaemia) and method of thrombolysis (agent, dose, and duration) varied between studies, making comparison more difficult. This review found no evidence of a difference between thrombolysis and surgery for treatment of acute limb ischaemia for our outcomes of interest. Those receiving thrombolysis treatment may be at higher risk of complications such as bleeding. The quality of data generated by the included studies is low.

10.1002/14651858.CD002784.pub3

cochrane-simplification-train-3540

cochrane-simplification-train-3540

Five trials (619 participants) met the inclusion criteria; two addressed inpatient rehabilitation (261 participants) and three (358 participants) home-based settings. There were no trials addressing outpatient centre-based programmes. Pooling of data was not possible due to differences in study design and outcomes used. Methodological assessment showed all trials were of low quality. For inpatient settings early commencement of rehabilitation and clinical pathways led to more rapid attainment of functional milestones (disability) (Functional Independence Measure (FIM) transfer WMD 0.5, 95% CI 0.15, 0.85, number needed to treat to benefit (NNTB) = 6, FIM ambulation WMD 1.55 (95%CI 0.96, 2.14), NNTB = 3), shorter hospital stay, fewer post-operative complications and reduced costs in the first three to four months. Home-based multidisciplinary care improved functional gain (Oxford Hip Score (OHS) WMD at 6 months -7.00 (95%CI -10.36, -3.64), NNT = 2 and quality of life (QoL) and reduced hospital stay in the medium term (six months). No trials addressed longer-term outcomes following hip replacement only. Based on the heterogeneity and the low quality of the included trials that precluded pooled meta-analysis, there is silver level evidence that following hip or knee joint replacement, early multidisciplinary rehabilitation can improve outcomes at the level of activity and participation. The optimal intensity, frequency and effects of rehabilitation over a longer period and associated social costs need further study. Future research should focus on improving methodological and scientific rigour of clinical trials, and use of standardised outcome measures, so that results can be pooled for statistical analysis.

Five trials (619 participants) met the inclusion criteria; two addressed inpatient rehabilitation (261 participants) and three (358 participants) home-based settings. There were no trials addressing outpatient centre-based programmes. Pooling of data was not possible due to differences in study design and outcomes used. Methodological assessment showed all trials were of low quality. For inpatient settings early commencement of rehabilitation and clinical pathways led to more rapid attainment of functional milestones (disability) (Functional Independence Measure (FIM) transfer WMD 0.5, 95% CI 0.15, 0.85, number needed to treat to benefit (NNTB) = 6, FIM ambulation WMD 1.55 (95%CI 0.96, 2.14), NNTB = 3), shorter hospital stay, fewer post-operative complications and reduced costs in the first three to four months. Home-based multidisciplinary care improved functional gain (Oxford Hip Score (OHS) WMD at 6 months -7.00 (95%CI -10.36, -3.64), NNT = 2 and quality of life (QoL) and reduced hospital stay in the medium term (six months). No trials addressed longer-term outcomes following hip replacement only. Based on the heterogeneity and the low quality of the included trials that precluded pooled meta-analysis, there is silver level evidence that following hip or knee joint replacement, early multidisciplinary rehabilitation can improve outcomes at the level of activity and participation. The optimal intensity, frequency and effects of rehabilitation over a longer period and associated social costs need further study. Future research should focus on improving methodological and scientific rigour of clinical trials, and use of standardised outcome measures, so that results can be pooled for statistical analysis.

10.1002/14651858.CD004957.pub3

cochrane-simplification-train-3541

cochrane-simplification-train-3541

We included 32 RCTs involving 2762 participants in this review. We considered 16 trials, representing 57% of all participants, to have a low risk of bias based on the Cochrane Back Review Group's 'Risk of bias' tool. For people with mixed symptom patterns (acute, subacute and chronic LBP with and without sciatica), there was low- to moderate-quality evidence that traction may make little or no difference in pain intensity, functional status, global improvement or return to work when compared to placebo, sham traction or no treatment. Similarly, when comparing the combination of physiotherapy plus traction with physiotherapy alone or when comparing traction with other treatments, there was very-low- to moderate-quality evidence that traction may make little or no difference in pain intensity, functional status or global improvement. For people with LBP with sciatica and acute, subacute or chronic pain, there was low- to moderate-quality evidence that traction probably has no impact on pain intensity, functional status or global improvement. This was true when traction was compared with controls and other treatments, as well as when the combination of traction plus physiotherapy was compared with physiotherapy alone. No studies reported the effect of traction on return to work. For chronic LBP without sciatica, there was moderate-quality evidence that traction probably makes little or no difference in pain intensity when compared with sham treatment. No studies reported on the effect of traction on functional status, global improvement or return to work. Adverse effects were reported in seven of the 32 studies. These included increased pain, aggravation of neurological signs and subsequent surgery. Four studies reported that there were no adverse effects. The remaining studies did not mention adverse effects. These findings indicate that traction, either alone or in combination with other treatments, has little or no impact on pain intensity, functional status, global improvement and return to work among people with LBP. There is only limited-quality evidence from studies with small sample sizes and moderate to high risk of bias. The effects shown by these studies are small and are not clinically relevant. Implications for practice To date, the use of traction as treatment for non-specific LBP cannot be motivated by the best available evidence. These conclusions are applicable to both manual and mechanical traction. Implications for research Only new, large, high-quality studies may change the point estimate and its accuracy, but it should be noted that such change may not necessarily favour traction. Therefore, little priority should be given to new studies on the effect of traction treatment alone or as part of a package.

The evidence is current to August 2012. The review included 32 studies and 2762 people with LBP. Most studies included a similar population of people with LBP with and without sciatica. The majority of studies included people with acute, subacute and chronic LBP. Most studies reported follow-up of one to 16 weeks, and a limited number of studies reported long-term follow-up of six months to one year. The included studies show that traction as a single treatment or in combination with physiotherapy is no more effective in treating LBP than sham (pretend) treatment, physiotherapy without traction or other treatment methods including exercise, laser, ultrasound and corsets. These conclusions are valid for people with and without sciatica. There was no difference regarding the type of traction (manual or mechanical). Side effects were reported in seven of the 32 studies and included increased pain, aggravation of neurological signs and subsequent surgery. Four studies reported that there were no side effects. The remaining studies did not mention side effects. The quality of the evidence ranged from very low to moderate. There was a scarcity of high-quality studies, especially those that distinguished between people with different symptom patterns (with and without sciatica, with pain of different duration).

10.1002/14651858.CD003010.pub5

cochrane-simplification-train-3542

cochrane-simplification-train-3542

Seven studies met the inclusion criteria. No studies had investigated selective inclusion of results in systematic reviews, or discrepancies in outcomes and analyses between systematic review registry entries and published systematic reviews. Based on a meta-analysis of four studies (including 485 Cochrane Reviews), 38% (95% confidence interval (CI) 23% to 54%) of systematic reviews added, omitted, upgraded or downgraded at least one outcome between the protocol and published systematic review. The association between statistical significance and discrepant outcome reporting between protocol and published systematic review was uncertain. The meta-analytic estimate suggested an increased risk of adding or upgrading (i.e. changing a secondary outcome to primary) when the outcome was statistically significant, although the 95% CI included no association and a decreased risk as plausible estimates (RR 1.43, 95% CI 0.71 to 2.85; two studies, n = 552 meta-analyses). Also, the meta-analytic estimate suggested an increased risk of downgrading (i.e. changing a primary outcome to secondary) when the outcome was statistically significant, although the 95% CI included no association and a decreased risk as plausible estimates (RR 1.26, 95% CI 0.60 to 2.62; two studies, n = 484 meta-analyses). None of the included studies had investigated whether the association between statistical significance and adding, upgrading or downgrading of outcomes was modified by the type of comparison, direction of effect or type of outcome; or whether there is an association between direction of the effect estimate and discrepant outcome reporting. Several secondary outcomes were reported in the included studies. Two studies found that reasons for discrepant outcome reporting were infrequently reported in published systematic reviews (6% in one study and 22% in the other). One study (including 62 Cochrane Reviews) found that 32% (95% CI 21% to 45%) of systematic reviews did not report all primary outcomes in the abstract. Another study (including 64 Cochrane and 118 non-Cochrane reviews) found that statistically significant primary outcomes were more likely to be completely reported in the systematic review abstract than non-significant primary outcomes (RR 2.66, 95% CI 1.81 to 3.90). None of the studies included systematic reviews published after 2009 when reporting standards for systematic reviews (Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement, and Methodological Expectations of Cochrane Intervention Reviews (MECIR)) were disseminated, so the results might not be generalisable to more recent systematic reviews. Discrepant outcome reporting between the protocol and published systematic review is fairly common, although the association between statistical significance and discrepant outcome reporting is uncertain. Complete reporting of outcomes in systematic review abstracts is associated with statistical significance of the results for those outcomes. Systematic review outcomes and analysis plans should be specified prior to seeing the results of included studies to minimise post-hoc decisions that may be based on the observed results. Modifications that occur once the review has commenced, along with their justification, should be clearly reported. Effect estimates and CIs should be reported for all systematic review outcomes regardless of the results. The lack of research on selective inclusion of results in systematic reviews needs to be addressed and studies that avoid the methodological weaknesses of existing research are also needed.

A systematic review summarises evidence from multiple studies to answer a specific research question (e.g. what are the benefits and harms of a particular intervention for a particular health condition?). Often, there are many outcomes that systematic review authors could report to address their research question (e.g. pain, disability and quality of life for patients with musculoskeletal conditions) and many different results available for a particular outcome (e.g. a study might measure pain using three different scales at four time points). If the decision about which outcomes to investigate in a systematic review is made based on the results for those outcomes in the eligible studies, this may lead to bias. While, if the decision about which outcomes to report in a systematic review and the ways to report them is based on the results, this may mislead users of the systematic review. This methodology review summarises the findings of studies examining the inclusion of results and reporting of outcomes in systematic reviews. We searched for studies indexed in electronic bibliographic databases up to May 2013. We included seven studies and found that outcomes investigated and reported in systematic reviews were often changed between the protocol and published systematic review. We also found that it was unclear whether the decision to make these changes was related to how statistically convincing the treatment effect for that outcome was. More studies are needed to confirm if this relationship exists. Also, one study found that some systematic reviews did not report all of the most important outcomes in the abstract of the review. Another study found that outcomes with a more statistically convincing result were more likely to be completely reported in the abstract than other outcomes. The studies that we included were limited to systematic reviews published before 2009. New studies are needed to examine the inclusion of results and reporting of outcomes in more recent systematic reviews.

10.1002/14651858.MR000035.pub2

cochrane-simplification-train-3543

cochrane-simplification-train-3543

The search identified 2178 citations, 28 of which were considered potentially relevant. After independent review of the full text of these studies, no eligible studies were identified for inclusion in this review due to the absence of studies with a randomised controlled study design. There was no evidence available to support conclusions about the effectiveness of nursing handover styles for ensuring continuity of information in hospitalised patients because we found no studies that fulfilled the methodological criteria for this review. As a consequence, uncertainty about the most effective practice remains. Research efforts should focus on strengthening the evidence abut the effectiveness of nursing handover styles using well designed, rigorous studies. According to current knowledge, the following guiding principles can be applied when redesigning the nursing handover process: face-to-face communication, structured documentation, patient involvement and use of IT technology to support the process.

This review tried to find out which nursing handover style works best. In March 2013 the review authors conducted a wide search for suitable relevant studies (randomised controlled studies) that compared different styles of nursing handover. However, they were not able to identify any randomised controlled studies that investigated the question, and so could draw no conclusions. Further research in this area is urgently needed.

10.1002/14651858.CD009979.pub2

cochrane-simplification-train-3544

cochrane-simplification-train-3544

We included 31 studies that explored the views and experiences of different types of SBAs, including doctors, midwives, nurses, auxiliary nurses and their managers. The included studies took place in Africa, Asia, and Latin America. Our synthesis pointed to a number of factors affecting SBAs’ provision of quality care. The following factors were based on evidence assessed as of moderate to high confidence. Skilled birth attendants reported that they were not always given sufficient training during their education or after they had begun clinical work. Also, inadequate staffing of facilities could increase the workloads of skilled birth attendants, make it difficult to provide supervision and result in mothers being offered poorer care. In addition, SBAs did not always believe that their salaries and benefits reflected their tasks and responsibilities and the personal risks they undertook. Together with poor living and working conditions, these issues were seen to increase stress and to negatively affect family life. Some SBAs also felt that managers lacked capacity and skills, and felt unsupported when their workplace concerns were not addressed. Possible causes of staff shortages in facilities included problems with hiring and assigning health workers to facilities where they were needed; lack of funding; poor management and bureaucratic systems; and low salaries. Skilled birth attendants and their managers suggested factors that could help recruit, keep, and motivate health workers, and improve the quality of care; these included good-quality housing, allowances for extra work, paid vacations, continuing education, appropriate assessments of their work, and rewards. Skilled birth attendants’ ability to provide quality care was also limited by a lack of equipment, supplies, and drugs; blood and the infrastructure to manage blood transfusions; electricity and water supplies; and adequate space and amenities on maternity wards. These factors were seen to reduce SBAs’ morale, increase their workload and infection risk, and make them less efficient in their work. A lack of transport sometimes made it difficult for SBAs to refer women on to higher levels of care. In addition, women’s negative perceptions of the health system could make them reluctant to accept referral. We identified some other factors that also may have affected the quality of care, which were based on findings assessed as of low or very low confidence. Poor teamwork and lack of trust and collaboration between health workers appeared to negatively influence care. In contrast, good collaboration and teamwork appeared to increase skilled birth attendants’ motivation, their decision-making abilities, and the quality of care. Skilled birth attendants’ workloads and staff shortages influenced their interactions with mothers. In addition, poor communication undermined trust between skilled birth attendants and mothers. Many factors influence the care that SBAs are able to provide to mothers during childbirth. These include access to training and supervision; staff numbers and workloads; salaries and living conditions; and access to well-equipped, well-organised healthcare facilities with water, electricity, and transport. Other factors that may play a role include the existence of teamwork and of trust, collaboration, and communication between health workers and with mothers. Skilled birth attendants reported many problems tied to all of these factors.

We included 31 studies conducted in Africa, Asia, and Latin America. Participants were skilled birth attendants including doctors, midwives, nurses, auxiliary nurses and their managers. Our synthesis pointed to several factors that affected skilled birth attendants’ provision of quality care. The following factors are based on evidence assessed as of moderate to high confidence. Skilled birth attendants reported that they sometimes had insufficient training during their education or after they had begun work. Where facilities lacked staff, skilled birth attendants’ workloads could increase, it could become difficult to provide supervision, and mothers could receive poorer care. In addition, skilled birth attendants did not always believe that their salaries and benefits reflected their tasks and responsibilities and the personal risks they undertook. Together with poor living and working conditions, these issues could lead to stress and affect skilled birth attendants' family life. Some skilled birth attendants felt that managers lacked capacity and skills, and they felt unsupported when their workplace concerns were not addressed. Possible causes of staff shortages included problems with hiring and assigning health workers to health facilities; lack of funding; poor management and bureaucratic systems; and low salaries. Skilled birth attendants and their managers suggested factors that could help recruit, keep, and motivate health workers, and improve the quality of their work; these included good-quality housing, allowances for extra work, paid vacations, continued education, proper assessments of their work, and rewards. Skilled birth attendants’ ability to provide quality care was also limited by a lack of equipment, drugs, and supplies; blood and the infrastructure to manage blood transfusions; electricity and water supplies; and adequate space and amenities on maternity wards. These factors were seen to reduce skilled birth attendants’ morale, increase their workload and infection risk, and make them less efficient in their work. A lack of transport sometimes made it difficult for skilled birth attendants to refer women to higher levels of care. In addition, women’s negative perceptions of the health system could make them reluctant to accept referral. We identified some other factors that also may have affected the quality of care, which were based on findings assessed as of low or very low confidence. Poor teamwork and lack of trust and collaboration between health workers appeared to negatively influence care. In contrast, good collaboration and teamwork appeared to increase skilled birth attendants’ motivation, their decision-making abilities, and the quality of care. Skilled birth attendants’ workloads and staff shortages influenced their interactions with mothers. In addition, poor communication undermined trust between skilled birth attendants and mothers. We searched for studies published before November 2016.

10.1002/14651858.CD011558.pub2

cochrane-simplification-train-3545

cochrane-simplification-train-3545

We included 5 randomised trials with 662 participants out of 93 publications identified through the literature searches. The number of deaths was 47 in the wait-and-see group (334 patients) compared to 26 in the prophylactic cholecystectomy group (328 patients) for a 78% increased risk of mortality (RR 1.78, 95% CI 1.15 to 2.75, P = 0.010). The survival benefit of prophylactic cholecystectomy was independent of trial design, inclusion of high risk patients or inclusion of any one of the five trials. Patients in the wait-and-see group had higher rates of recurrent biliary pain (RR 14.56, 95% CI 4.95 to 42.78, P < 00001), jaundice or cholangitis (RR 2.53, 95% CI 1.09 to 5.87, P = 0.03), and of repeat ERCP or other forms of cholangiography (RR 2.36, 95% CI 1.29 to 4.32, P = 0.005). Cholecystectomy was eventually performed in 35% (115 patients) of the wait-and-see group. Prophylactic cholecystectomy should be offered to patients whose gallbladders remain in-situ after endoscopic sphincterotomy and common bile duct clearance.

We included 5 randomised trials with 662 participants out of 93 publications identified through the literature searches. The number of deaths was 47 in the wait-and-see group (334 patients) compared with 26 in the prophylactic cholecystectomy group (328 patients). This review of randomised clinical trials suggests that early removal of the gallbladder decreases the risk of death or of complications from gallstones. The number of patients (662) reviewed in this report prevents some of the subgroup analyses from being conclusive. Further clinical trials, particularly of high-risk patients, would solve this problem.

10.1002/14651858.CD006233.pub2

cochrane-simplification-train-3546

cochrane-simplification-train-3546

Two studies (involving 286 women) from amniocentesis (but none from CVS) compared the impact of communicating results of rapid testing with waiting for definitive karyotype. Unfortunately, it was not possible to perform pooled analysis because one study reported only median (interquartile range) data, presumably because the data were not normally distributed. One study reported a statistically significant reduction in the average anxiety during the waiting period for women who had had a rapid test compared with those who had not (mean difference (MD) -2.30, 95% confidence intervals (CI) -3.08 to - 1.52). The other study compared median (interquartile range) for the trait- and state-anxiety scores and found no difference between the two groups. We found no conclusive evidence that, while waiting for the full karyotype following amniocentesis, issuing results from a rapid analysis reduces maternal anxiety. The limited evidence from the two trials included in this review does not help resolve the dilemma about whether full karyotyping should be abandoned in favour of limited rapid testing for women undergoing Down's syndrome screening. This choice will rest on clinical arguments and cost-effectiveness rather than impact on anxiety. There is also no evidence to support the view that issuing amniocentesis results as soon as they are available is more user friendly than using a pre-defined fixed date. Studies evaluating the effect of different strategies for disclosing results on women anxiety for CVS are needed.

One study reported a statistically significant reduction in the average anxiety during the waiting period for women who had had a rapid test, but the other found no difference between the two groups. There was also no evidence to support the view that issuing amniocentesis results as soon as they are available is more user friendly than informing women on a pre-defined fixed date. The results remain inconclusive and, therefore, for the time being the choice of communication strategies should be influenced by clinical arguments and cost-effectiveness rather than impact on anxiety. Studies evaluating the effect of different strategies for disclosing results on women anxiety for chorionic villous sampling are needed.

10.1002/14651858.CD007750.pub2

cochrane-simplification-train-3547

cochrane-simplification-train-3547

We include 10 RCTs (n = 1850); almost all participants had moderate or severe ARDS. For the primary analysis, the risk of bias was low in three studies and unclear in five studies; the overall quality of evidence was very low due to imprecision, inconsistency, indirectness and methodologic limitations. In participants randomized to HFO, there was no significant difference in hospital or 30-day mortality (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.72 to 1.16; P = 0.46, I² = 66%; 8 trials, 1779 participants, 807 deaths) compared with conventional ventilation. One large multicentre RCT was terminated early because of increased mortality in participants randomized to HFO compared to mechanical ventilation with low tidal volume and high positive end expiratory pressure, with HFO reserved only as a rescue therapy. We found substantial between-trial statistical heterogeneity (I² = 0% to 66%) for clinical outcomes, including mortality. The findings of this systematic review suggest that HFO does not reduce hospital and 30-day mortality due to ARDS; the quality of evidence was very low. Our findings do not support the use of HFO as a first-line strategy in people undergoing mechanical ventilation for ARDS.

We included 10 randomized controlled trials (RCTs) enrolling 1850 participants in this updated review. One large trial was stopped early because of increased deaths among participants who were randomized to HFO. Four trials reported at least some funding from manufacturers of HFO ventilators. HFO did not reduce the risk of death in hospital in eight trials enrolling 1779 participants. The ability of the lungs to oxygenate blood, measured at 24 to 72 hours of ventilation after randomization, was 18% to 26% better in participants receiving HFO. HFO had no effect on the length of time an artificial breathing machine was required. The risk of unwanted side effects, including low blood pressure or further injury to the lung due to high airway pressure, was not increased. We found substantial inconsistency among clinical trials which reported the effect of HFO on the risk of death in participants with ARDS. The quality of evidence is very low for outcomes that would be most important to patients. This is because of a lack of precision and consistency, and because in many cases the methods used by investigators during clinical trials were not of the highest standard. This indicates that there is considerable uncertainty regarding the effect of HFO on death. Additional randomized trials could change these findings.

10.1002/14651858.CD004085.pub4

cochrane-simplification-train-3548

cochrane-simplification-train-3548

We included six RCTs (692 participants). The overall risk of bias in the studies was low. Two studies assessed oral administration of tranexamic acid, given regularly over several days, and compared it to placebo. In the other four studies, a single application of topical tranexamic acid was compared with placebo (one study) and a combination of epinephrine and lidocaine or phenylephrine (three studies). All participants were adults. Tranexamic acid versus placebo For our primary outcome, control of epistaxis: re-bleeding (proportion re-bleeding within 10 days), we were able to pool data from three studies. The pooled result demonstrated a benefit of tranexamic acid compared to placebo, the risk of re-bleeding reducing from 67% to 47% (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.56 to 0.90; three studies; 225 participants; moderate-quality evidence). When we compared the effects of oral and topical tranexamic acid separately the risk of re-bleeding with oral tranexamic acid reduced from 69% to 49%, RR 0.73 (95% CI 0.55 to 0.96; two studies, 157 participants; moderate-quality evidence) and with topical tranexamic acid it reduced from 66% to 43%, RR 0.66 (95% CI 0.41 to 1.05; single study, 68 participants). We rated the quality of evidence provided by the single study as low, therefore it is uncertain whether topical tranexamic acid is effective in stopping bleeding in the 10-day period after a single application. No study specifically sought to identify and report our primary outcome: significant adverse effects (i.e. seizures, thromboembolic events). The secondary outcome time to stop initial bleeding (proportion with bleeding controlled within 30 minutes) was measured in one study using topical tranexamic acid and there was no evidence of a difference at 30 minutes (RR 0.79, 95% CI 0.56 to 1.11; 68 participants; low-quality evidence). No studies reported the proportion of patients requiring any further intervention (e.g. repacking, surgery, embolisation). One study of oral tranexamic acid reported the proportion of patients requiring blood transfusion and found no difference between groups: 5/45 (11%) versus 6/44 (14%) (RR 0.81, 95% CI 0.27 to 2.48; 89 participants; low-quality evidence). Two studies reported hospital length of stay. One study reported a significantly shorter stay in the oral tranexamic acid group (mean difference (MD) -1.60 days, 95% CI -2.49 to -0.71; 68 participants). The other study found no evidence of a difference between the groups. Tranexamic acid versus other haemostatic agents When we pooled the data from three studies the proportion of patients whose bleeding stopped within 10 minutes was significantly higher in the topical tranexamic acid group compared to the group receiving another haemostatic agent (70% versus 30%: RR 2.35, 95% CI 1.90 to 2.92; 460 participants) (moderate-quality evidence). Adverse effects across all studies Five studies recorded 'adverse effects' in a general way. None found any difference between the groups in the occurrence of minor adverse effects (e.g. mild nausea and diarrhoea, 'bad taste' of gel). In one study a patient developed a superficial thrombophlebitis of both legs following discharge, however it is not reported in which group this occurred. No "other serious adverse effect" was reported in any study. We found moderate-quality evidence that there is probably a reduction in the risk of re-bleeding with the use of either oral or topical tranexamic acid in addition to usual care in adult patients with epistaxis, compared to placebo with usual care. However, the quality of evidence relating solely to topical tranexamic acid was low (one study only), so we are uncertain whether or not topical tranexamic acid is effective in stopping bleeding in the 10-day period after a single application. We found moderate-quality evidence that topical tranexamic acid is probably better than other topical agents in stopping bleeding in the first 10 minutes. There have been only three RCTs on this subject since 1995. Since then there have been significant changes in nasal cauterisation and packing techniques (for example, techniques including nasal endoscopy and more invasive approaches such as endoscopic sphenopalatine artery ligation). New trials would inform us about the effectiveness of tranexamic acid in light of these developments.

We searched for randomised controlled trials in patients of any age with nosebleed requiring intervention. Patients were treated with tranexamic acid (in addition to usual care) compared to placebo, no treatment or any other agent used to stop bleeding. We found six studies that met our inclusion criteria, with a total of 692 participants. Two studies used oral administration of tranexamic acid and four used topical administration. All participants in the studies were adults. Three of the six studies were conducted over 20 years ago. Three studies measured re-bleeding within 10 days. When we combined the results we found that fewer patients who were given either oral or topical tranexamic acid had further episodes of re-bleeding following an initial nosebleed compared to those treated with usual care. The time to stop initial bleeding (control of bleeding within 30 minutes) was measured in four studies. In three studies the proportion of patients whose bleeding stopped within 10 minutes was significantly higher in the group receiving topical tranexamic acid compared to the group receiving a different drug (topical epinephrine and lidocaine or phenylephrine). In the other study there was no significant difference at 30 minutes when topical tranexamic acid was compared with placebo. No studies reported the proportion of patients requiring any further intervention (e.g. repacking, surgery). Only one study of oral tranexamic acid reported the proportion of patients requiring a blood transfusion and there was no evidence of a difference between the groups. Length of hospital stay was reported in two studies. One study reported a significantly shorter stay in the oral tranexamic acid group, while the other found no evidence of a difference. Five studies mention recording "adverse effects". None found any difference between the groups in the occurrence of minor adverse effects (e.g. mild nausea and diarrhoea, 'bad taste' of gel). In one study a patient did develop a superficial thrombophlebitis (inflammation and a blood clot in a vein near the surface of the skin) of both legs following discharge, but the study did not report in which treatment group this happened. No serious adverse event was seen in any of the studies. Overall, the risk of bias in the six studies was low. We graded the quality of the evidence for the main outcome (control of epistaxis: re-bleeding within 10 days) as moderate, which means that further research is likely to have an important impact on our confidence in the estimate of the effect and is likely to change the estimate. In light of this and the fact that 'usual care' has changed, with the development of more modern nasal cauterisation and packing techniques, since three of the included studies were carried out, there remains uncertainty about the role of tranexamic acid in the treatment of patients with epistaxis. Newer research into the effect of tranexamic acid as a treatment for nosebleeds would inform future management decisions for this condition. The evidence in this review is up to date to October 2018.

10.1002/14651858.CD004328.pub3

cochrane-simplification-train-3549

cochrane-simplification-train-3549

One double blind randomised crossover trial met the inclusion criteria and compared 5% albumin to normal saline in patients with a previous history of IDH. Results from 45 assessable participants did not lead to rejection of the null hypothesis of no difference between 5% albumin and normal saline in the primary outcome measure of percentage target ultrafiltration achieved, nor in 11/12 secondary outcomes. Additional (unblinded) saline was given less often when 5% albumin was used compared with saline (16% versus 36%, P = 0.04). However, the volume of additional fluid administered was similar in both groups. There were no significant differences in the nursing time required to treat IDH and the time to restore BP. No randomised or controlled trial was identified comparing albumin to crystalloids (other than normal saline) or non-protein colloids, or a combination of both, in the treatment of symptomatic hypotension during dialysis. One double blind crossover RCT in 45 assessable patients showed that 5% albumin is not superior to normal saline for the treatment of symptomatic hypotension in maintenance haemodialysis patients with a previous history of IDH. Given the cost and relative rarity of albumin use compared to saline, saline should be first line of therapy for treatment of IDH in stable dialysis patients.

We found one trial comparing albumin to normal saline; no trials were found comparing albumin to other fluids used to treat hypotension. This trial showed no difference between albumin and normal saline in all outcomes except for the amount of additional saline given, which was less in the group treated with albumin. We concluded that normal saline should be the first choice for treating IDH.

10.1002/14651858.CD006758.pub2

cochrane-simplification-train-3550

cochrane-simplification-train-3550

We included three studies with a total of 122 children (62/60 in intervention/control arms) aged up to 12 months that investigated nasal CPAP compared with supportive (or "standard") therapy. We included one new trial (72 children) that contributed data to the assessment of respiratory rate and need for mechanical ventilation for this update. The included studies were single-centre trials conducted in France, the UK, and India. Two studies were parallel-group RCTs and one was a cross-over RCT. The evidence provided by the included studies was low quality; we assessed high risk of bias for blinding, incomplete outcome data, and selective reporting, and confidence intervals were wide. The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (3 RCTs, 122 children; risk ratio (RR) 0.69, 95% confidence interval (CI) 0.14 to 3.36; low-quality evidence). None of the trials measured time to recovery. Limited, low-quality evidence indicated that CPAP decreased respiratory rate (2 RCTs, 91 children; mean difference (MD) -3.81, 95% CI -5.78 to -1.84). Only one trial measured change in arterial oxygen saturation, and the results were imprecise (19 children; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on change in arterial partial carbon dioxide pressure (pCO₂) was imprecise (2 RCTs, 50 children; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low-quality evidence). Duration of hospital stay was similar in both CPAP and supportive care groups (2 RCTs, 50 children; MD 0.07 days, 95% CI -0.36 to 0.50; low-quality evidence). Two studies did not report about pneumothorax, but pneumothorax did not occur in one study. No studies reported occurrences of deaths. Several outcomes (change in partial oxygen pressure, hospital admission rate (from emergency department to hospital), duration of emergency department stay, and need for intensive care unit admission) were not reported in the included studies. Limited, low-quality evidence suggests that breathing improved (a decreased respiratory rate) in children with bronchiolitis who received CPAP; this finding is unchanged from the 2015 review. Further evidence for this outcome was provided by the inclusion of a low-quality study for the 2018 update. Due to the limited available evidence, the effect of CPAP in children with acute bronchiolitis is uncertain for other outcomes. Larger, adequately powered trials are needed to evaluate the effect of CPAP for children with acute bronchiolitis.

We included three small randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method) involving a total of 122 children aged up to 12 months who were diagnosed with bronchiolitis. We included one new low-quality trial with 72 children in this update. The three studies were conducted at single centres in France, the UK, and India. All studies compared CPAP with standard therapy. One study was funded by a university hospital; one reported that no funding was received; and one did not mention the funding source. Insufficient evidence was available to permit conclusions about the effect of CPAP on the need for mechanical ventilation in children with bronchiolitis. Limited, low-quality evidence indicated that breathing improved (respiratory rate decreased) in children who received CPAP. The length of time children spent in hospital was similar between the CPAP and the standard therapy groups. No children in the studies were reported to have died. The studies did not report on time to recovery, change in partial oxygen pressure, how often children were admitted to hospital from the emergency department, how long children were in the emergency department, and the need for intensive care admission. There were no local nasal effects, or shock as reported by one study. No children were reported to have had air in the cavity between the lungs and the chest wall, causing lung collapse (pneumothorax) as reported by one study. Two studies did not report about local nasal effects, shock, or pneumothorax. The study added for this update contributed data to the assessment of respiratory rate and need for mechanical ventilation. We found limited, low-quality evidence related to CPAP for children with bronchiolitis. Evidence quality was reduced due to high risk of bias, losses to follow-up, selective reporting, and the wide range of values reported by the included studies.

10.1002/14651858.CD010473.pub3

cochrane-simplification-train-3551

cochrane-simplification-train-3551

Twenty eight short-term (average of seven weeks) randomised controlled trials (740 participants) were included in the review, 20 of which investigated augmentation of medication for treatment-resistant obsessive compulsive disorder (OCD). Summary statistics for responder status from nine trials demonstrate overall superiority of a variety of medication agents to placebo (relative risk of non-response (RR) 3.16, 95% CI 1.08 to 9.23). Similarly, symptom severity was significantly reduced in the medication groups, relative to placebo (number of trials (N) = 14, standardised mean difference (SMD) -0.87, 95% CI -1.37 to -0.36). There is no evidence of a difference between medication and placebo in total dropout rate, or in the number of dropouts due to adverse events. Medication augmentation can be an effective and well-tolerated short-term treatment strategy for non-responders to first-line pharmacotherapy of anxiety disorders. However, any conclusions must be tentative in view of methodological and clinical heterogeneity, and the fact that much of the relevant database is based on antipsychotic augmentation trials in OCD patients resistant to serotonin reuptake inhibitors (SRIs). Additional data are needed to address several areas, including the efficacy of augmentation over the longer-term, and the value of medication augmentation in comparison to other strategies (eg switching medication, adding psychotherapy).

This was a systematic review of 28 short-term randomised controlled trials of medication augmentation for the treatment of such individuals (740 participants). A significantly larger proportion of patients responded to medication (31.8%) than to placebo (13.6%), (nine trials, 250 participants). Symptom severity was also significantly reduced (14 trials, 337 participants). A substantial proportion of the efficacy evidence base was for the augmentation with antipsychotics of serotonin reuptake inhibitors for obsessive compulsive disorder.

10.1002/14651858.CD005473.pub2

cochrane-simplification-train-3552

cochrane-simplification-train-3552

We included four RCTs with a total of 463 participants (aged 42 years to 93 years); one report was only available as a published abstract. Meta-analysis of three RCTs suggests an increase in the proportion of ulcers completely healed with sulodexide as an adjuvant to local treatment (including wound care and compression therapy) compared with local treatment alone (rate of complete healing with sulodexide 49.4% compared with 29.8% with local treatment alone; RR 1.66; 95% CI 1.30 to 2.12). This evidence for sulodexide increasing the rate of complete healing is low quality due to risk of bias. It is unclear whether sulodexide is associated with any increase in adverse events (4.4% with sulodexide versus 3.1% with no sulodexide; RR 1.44; 95% CI 0.48 to 4.34). The evidence for adverse events is very low quality, downgraded twice for risk of bias and once for imprecision. Sulodexide may increase the healing of venous ulcers, when used alongside local wound care, however the evidence is only low quality and the conclusion is likely to be affected by new research. It is not clear whether sulodexide is associated with adverse effects. The standard dosage, route and frequency of sulodexide reported in the trials was unclear. Further rigorous, adequately powered RCTs examining the effects of sulodexide on healing, ulcer recurrence, quality of life and costs are necessary.

The review includes four studies involving 463 people with venous leg ulcers aged between 42 and 93 years old. The studies compared sulodexide used in combination with local treatment (including wound care and compression therapy) with local treatment alone. The duration of the four studies ranged from one month to three months. Three studies (438 participants) indicated that sulodexide might help to improve ulcer healing, as the proportion of ulcers that were completely healed was increased from 29.8% with local treatment to 49.4% when the participants also received sulodexide. It is unclear whether sulodexide results in more adverse effects (4.4% with sulodexide versus 3.1% without sulodexide). The overall quality of evidence for each outcome varied between low and very low, due to risk of bias, and imprecision (that is, for some outcomes, results from only one, small study were available). This plain language summary is up to date as of 1 July 2015.

10.1002/14651858.CD010694.pub2

cochrane-simplification-train-3553

cochrane-simplification-train-3553

We included seven studies (662 participants) in this review. All except one study was assessed as being at high risk of bias. Three studies assessed atorvastatin, three assessed simvastatin and one investigated rosuvastatin. All studies collected data during the immediate perioperative period only; data collection to hospital discharge and postoperative biochemical data collection ranged from 24 hours to 7 days. Overall, pre-operative statin treatment was not associated with a reduction in postoperative AKI, need for RRT, or mortality. Only two studies (195 participants) reported postoperative SCr level. In those studies, patients allocated to receive statins had lower postoperative SCr concentrations compared with those allocated to no drug treatment/placebo (MD 21.2 µmol/L, 95% CI -31.1 to -11.1). Adverse effects were adequately reported in only one study; no difference was found between the statin group compared to placebo. Analysis of currently available data did not suggest that preoperative statin use is associated with decreased incidence of AKI in adults after surgery who required cardiac bypass. Although a significant reduction in SCr was seen postoperatively in people treated with statins, this result was driven by results from a single study, where SCr was considered as a secondary outcome. The results of the meta-analysis should be interpreted with caution; few studies were included in subgroup analyses, and significant differences in methodology exist among the included studies. Large high quality RCTs are required to establish the safety and efficacy of statins to prevent AKI after cardiac surgery.

This review aims to evaluate evidence on the use of statins at the time of heart surgery to investigate if use can help to prevent kidney failure and how well statins are tolerated among patients. We searched the literature to January 2015 and included seven studies that involved a total of 662 participants to inform our assessment. In these studies, patients planned for heart surgery received statins or placebo (or no treatment at all). Five studies (467 participants) reported rates of kidney failure. We found that there was a high risk of bias in six of the seven included studies. We found no difference in the rate of kidney failure between patients who received statins and those who did not. Two studies (195 patients) reported serum creatinine (a marker of kidney function) after the operation. We found that serum creatinine was lower in patients in the statin group (indicating better kidney function). Other conclusions were limited by the small number of studies. However, patients who received statins did not seem to need less dialysis. They did not have a higher rate of death in hospital and did not have an increased rate of adverse events.

10.1002/14651858.CD010480.pub2

cochrane-simplification-train-3554

cochrane-simplification-train-3554

Nineteen trials involving 10,667 women were included. Risk of bias in trials was difficult to assess accurately due to incomplete reporting. None of the evidence relating to our main outcomes was graded as high quality. The quality of evidence was downgraded due to missing information on trial methods, imprecision in risk estimates and heterogeneity. Eighteen of these studies compared the use of Doppler ultrasound of the umbilical artery of the unborn baby with no Doppler or with cardiotocography (CTG). One more recent trial compared Doppler examination of other fetal blood vessels (ductus venosus) with computerised CTG. The use of Doppler ultrasound of the umbilical artery in high-risk pregnancy was associated with fewer perinatal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2% versus 1.7 %, number needed to treat (NNT) = 203; 95% CI 103 to 4352, evidence graded moderate). The results for stillbirths were consistent with the overall rate of perinatal deaths, although there was no clear difference between groups for this outcome (RR 0.65, 95% CI 0.41 to 1.04; 15 studies, 9560 babies, evidence graded low). Where Doppler ultrasound was used, there were fewer inductions of labour (average RR 0.89, 95% CI 0.80 to 0.99, 10 studies, 5633 women, random-effects, evidence graded moderate) and fewer caesarean sections (RR 0.90, 95% CI 0.84 to 0.97, 14 studies, 7918 women, evidence graded moderate). There was no comparative long-term follow-up of babies exposed to Doppler ultrasound in pregnancy in women at increased risk of complications. No difference was found in operative vaginal births (RR 0.95, 95% CI 0.80 to 1.14, four studies, 2813 women), nor in Apgar scores less than seven at five minutes (RR 0.92, 95% CI 0.69 to 1.24, seven studies, 6321 babies, evidence graded low). Data for serious neonatal morbidity were not pooled due to high heterogeneity between the three studies that reported it (1098 babies) (evidence graded very low). The use of Doppler to evaluate early and late changes in ductus venosus in early fetal growth restriction was not associated with significant differences in any perinatal death after randomisation. However, there was an improvement in long-term neurological outcome in the cohort of babies in whom the trigger for delivery was either late changes in ductus venosus or abnormalities seen on computerised CTG. Current evidence suggests that the use of Doppler ultrasound on the umbilical artery in high-risk pregnancies reduces the risk of perinatal deaths and may result in fewer obstetric interventions. The results should be interpreted with caution, as the evidence is not of high quality. Serial monitoring of Doppler changes in ductus venosus may be beneficial, but more studies of high quality with follow-up including neurological development are needed for evidence to be conclusive.

We searched for evidence in March 2017. We found 19 trials involving over 10,000 women. Eighteen of these studies compared the use of Doppler ultrasound of the umbilical artery of the unborn baby with no Doppler or with cardiotocography (CTG, sometimes called electronic fetal monitoring). One more recent trial compared Doppler examination of other fetal blood vessels (ductus venosus) with computerised CTG (short-term variation). Evidence from included studies was assessed as moderate to very low-quality due to incomplete reporting of methods and uncertainty of findings; when the strength of the evidence is low or very low, this means future research may change the results and we cannot be certain about them. Results showed that Doppler ultrasound of the umbilical artery may decrease the number of babies who die, and may lead to fewer caesarean sections and inductions of labour. There was no clear difference in the number of stillbirths, births using forceps or ventouse, or babies with a low Apgar score five minutes after birth. Findings for serious problems in the neonate were not consistent in different studies. In babies with growth restriction, when the decision to deliver was based on late ductus venosus changes or abnormalities on computerised CTG, this appeared to improve long-term (two-year) developmental outcome. Doppler ultrasound in high-risk pregnancies appears to reduce the number of babies who die, and may also lead to fewer obstetric interventions. However, the evidence was of moderate to very low-quality. Further studies of high-quality with long-term follow-up would help us to be more certain.

10.1002/14651858.CD007529.pub4

cochrane-simplification-train-3555

cochrane-simplification-train-3555

We identified nine RCTs (587 participants) for inclusion in the review, of which three studies were found at this update. The sequence generation was inadequate in one study and not described in three studies. We performed two meta-analyses to evaluate the clinical (3 trials, 261 participants) and neurophysiological (2 trials, 101 participants) outcomes of simple decompression versus decompression with submuscular or subcutaneous transposition; four trials in total examined this comparison. We found no difference between simple decompression and transposition of the ulnar nerve for both clinical improvement (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.80 to 1.08; moderate-quality evidence) and neurophysiological improvement (mean difference (in m/s) 1.47, 95% CI -0.94 to 3.87). The number of participants to clinically improve was 91 out of 131 in the simple decompression group and 97 out of 130 in the transposition group. Transposition showed a higher number of wound infections (RR 0.32, 95% CI 0.12 to 0.85; moderate-quality evidence). In one trial (47 participants), the authors compared medial epicondylectomy with anterior transposition and found no difference in clinical and neurophysiological outcomes. In one trial (48 participants), the investigators compared subcutaneous transposition with submuscular transposition and found no difference in clinical outcomes. In one trial (54 participants for 56 nerves treated), the authors found no difference between endoscopic and open decompression in improving clinical function. One trial (51 participants) assessed conservative treatment in clinically mild or moderate UNE. Based on low-quality evidence, the trial authors found that information on avoiding prolonged movements or positions was effective in improving subjective discomfort. Night splinting and nerve gliding exercises in addition to information provision did not result in further improvement. One trial (55 participants) assessed the effectiveness of corticosteroid injection and found no difference versus placebo in improving symptoms at three months' follow-up. We found only two studies of treatment of ulnar neuropathy using conservative treatment as the comparator. The available comparative treatment evidence is not sufficient to support a multiple treatment meta-analysis to identify the best treatment for idiopathic UNE on the basis of clinical, neurophysiological, and imaging characteristics. We do not know when to treat a person with this condition conservatively or surgically. Moderate-quality evidence indicates that simple decompression and decompression with transposition are equally effective in idiopathic UNE, including when the nerve impairment is severe. Decompression with transposition is associated with more deep and superficial wound infections than simple decompression, also based on moderate-quality evidence. People undergoing endoscopic surgery were more likely to have a haematoma. Evidence from one small RCT of conservative treatment showed that in mild cases, information on movements or positions to avoid may reduce subjective discomfort.

We found two randomised controlled trials (RCTs) of nonsurgical treatment. One RCT compared three groups of people with mild or moderate UNE (51 people in total). All three groups received written instructions to avoid movements or positions that provoked symptoms. The second group had the same information with elbow splints at night for three months. The third group had the same information with nerve gliding exercises. The other nonsurgical study (55 people) compared a corticosteroid injection with a sham injection. Seven RCTs compared different surgical methods: • simple decompression or transposition of the nerve (submuscular or subcutaneous transposition) (4 trials, 327 participants); • medial epicondylectomy or anterior transposition (1 trial, 47 participants); • anterior subcutaneous transposition or anterior submuscular transposition (1 trial, 48 participants); • keyhole or open surgery (1 trial, 54 participants with 56 trapped nerves). Written information alone was as effective in improving work activities and reducing pain at night as when people also used splints or did exercises. Researchers found no evidence that corticosteroid injection was effective in improving symptoms of UNE. We were able to combine results from three trials comparing two surgical techniques: simple decompression and transposition of the ulnar nerve (subcutaneous or submuscular). We found no important difference in symptom scores between the techniques at 6 to 12 months. Decompression with transposition may result in more deep and superficial wound infections. Trialists found no clinical differences between surgical techniques in the other surgical trials. People undergoing endoscopic surgery were more likely to have a haematoma (an abnormal collection of blood) after surgery. Evidence was insufficient for us to choose the best treatment for UNE. However, we did find that in mild cases, information on movements and positions to avoid may reduce discomfort. Moreover, the combined results from three surgical trials provided moderate-quality evidence that simple decompression surgery and decompression with transposition may be equally effective, but that decompression with transposition may result in more deep and superficial wound infections. The evidence is up to date to 31 May 2016.

10.1002/14651858.CD006839.pub4

cochrane-simplification-train-3556

cochrane-simplification-train-3556

We included 10 trials with a total of 3417 women randomised. Seven of these trials, recruiting 2629 women, contributed data to the review. However, results for all outcomes were based on single studies. There was limited evidence for the primary outcomes of reduction of episodes of violence (physical, sexual, and/or psychological) and prevention of violence during and up to one year after pregnancy (as defined by the authors of trials). In one study, women who received the intervention reported fewer episodes of partner violence during pregnancy and in the postpartum period (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.43 to 0.88, 306 women, moderate quality). Groups did not differ for Conflict Tactics Score - the mean partner abuse scores in the first three months postpartum (mean difference (MD) 4.20 higher, 95% CI -10.74 to 19.14, one study, 46 women, very low quality). The Current Abuse Score for partner abuse in the first three months was also similar between groups (MD -0.12 lower, 95% CI -0.31 lower to 0.07 higher, one study, 191 women, very low quality). Evidence for the outcomes episodes of partner abuse during pregnancy or episodes during the first three months postpartum was not significant (respectively, RR 0.50, 95% CI 0.25 to 1.02, one study with 220 women, very low quality; and RR 0.60, 95% CI 0.35 to 1.04, one study, 271 women, very low quality). Finally, the risk for low birthweight (< 2500 g) did not differ between groups (RR 0.74, 95 % CI 0.41 to 1.32, 306 infants, low quality). There were few statistically significant differences between intervention and control groups for depression during pregnancy and the postnatal period. Only one study reported findings for neonatal outcomes such as preterm delivery and birthweight, and there were no clinically significant differences between groups. None of the studies reported results for other secondary outcomes: Apgar score less than seven at one minute and five minutes, stillbirth, neonatal death, miscarriage, maternal mortality, antepartum haemorrhage, and placental abruption. There is insufficient evidence to assess the effectiveness of interventions for domestic violence on pregnancy outcomes. There is a need for high-quality, RCTs with adequate statistical power to determine whether intervention programs prevent or reduce domestic violence episodes during pregnancy, or have any effect on maternal and neonatal mortality and morbidity outcomes.

Routine prenatal care offers opportunities for healthcare staff to identify women at risk of being abused. In this review we included 10 randomised trials involving a total of 3417 women, seven of which studied pregnant women who were at high risk of partner violence. The interventions examined in the studies included a single brief individualised consultation, case management and referral to a social care worker, and multiple therapy sessions during pregnancy and after birth. Due to the lack of data, and the different way outcomes were reported, we were unable to identify interventions that worked better than others. Studies focused on different outcomes and we were not able to pool information to draw conclusions about the overall effectiveness of the interventions. Most of the studies did not report on whether or not there had been any reduction in episodes of violence. There was evidence from a single study that the total number of women reporting partner violence during pregnancy and after birth was reduced for women receiving a psychological therapy intervention. Several of the studies examined whether women who received interventions were less likely to have depression after the birth of the baby, but the evidence was not consistent. Other outcomes for the baby such as reduced birthweight and preterm birth were reported in only one study, and the intervention did not lessen the risk of preterm birth (< 2500 g). None of the studies reported results for important outcomes such as stillbirth, neonatal death, miscarriage, maternal deaths, antepartum haemorrhage, and placental abruption. More information is needed from well-conducted trials before any particular interventional approach can be recommended.

10.1002/14651858.CD009414.pub3

cochrane-simplification-train-3557

cochrane-simplification-train-3557

Twelve trials were included (2514 patients, average follow-up six years), 11 using selegiline. The methodological quality was reasonable although concealment of allocation was definitely adequate in only five trials. MAO-B inhibitors were not associated with a significant increase in deaths (odds ratio (OR) 1.12; 95% confidence interval (CI) 0.90 to 1.41). They provided small benefits over control in impairment (weighted mean difference (WMD) for change in motor UPDRS score 3.79 points less with MAO-B inhibitors; 95% CI 2.27 to 5.30) and disability (WMD for change in UPDRS ADL score 1.49 less; 95% CI 0.49 to 2.49) at one year which may not be clinically significant. There was a levodopa-sparing effect with MAO-B inhibitors, which was associated with a significant reduction in motor fluctuations (OR 0.73; 95% CI 0.58 to 0.91) but not dyskinesia (OR 0.96; 95% CI 0.76 to 1.22). The reduction in motor fluctuations was, however, not robust in sensitivity analyses. There was a trend to more withdrawals due to adverse events with MAO-B inhibitors (OR 1.72; 95% CI 0.98 to 3.01). MAO-B inhibitors (more specifically selegiline which contributes most of the data) do not appear to delay disease progression in terms of improved survival but may reduce later motor fluctuations. At present, we do not feel these drugs can be recommended for routine use in the treatment of early Parkinson's disease.

We reviewed 11 controlled trials with a total of 2514 patients that compared giving MAO-B inhibitors with not giving them in people with early Parkinson's to see if it was safe and effective. The results show that, although MAO-B inhibitors do improve symptoms of Parkinson's and delay the need for levodopa by a few months, they are too weak to have a major effect and do not seem to delay the progression of the condition. They may, however, reduce motor fluctuations although more information is needed to be certain of this. Although they can cause some side-effects, these are generally mild.

10.1002/14651858.CD004898.pub2

cochrane-simplification-train-3558

cochrane-simplification-train-3558

We included 14 RCTs that evaluated a range of interventions across different settings. The study methods were generally poorly described, and consequently all included trials were judged to be at high or unclear risk of selection and reporting bias. Only seven trials reported clinical outcome data which limits our ability to make broad generalizations to different epidemiological settings and cultures. Cutaneous leishmaniasis One four-arm RCT from Afghanistan compared indoor residual spraying (IRS), insecticide-treated bednets (ITNs), and insecticide-treated bedsheets, with no intervention. Over 15 months follow-up, all three insecticide-based interventions had a lower incidence of CL than the control area (IRS: risk ratio (RR) 0.61, 95% confidence interval (CI) 0.38 to 0.97, 2892 participants, moderate quality evidence; ITNs: RR 0.32, 95% CI 0.18 to 0.56, 2954 participants, low quality evidence; ITS: RR 0.34, 95% CI 0.20 to 0.57, 2784 participants, low quality evidence). No difference was detected between the three interventions (low quality evidence). One additional trial of ITNs from Iran was underpowered to show a difference. Insecticide treated curtains were compared with no intervention in one RCT from Venezuela, where there were no CL episodes in the intervention areas over 12 months follow-up compared to 142 in control areas (RR 0.00, 95% CI 0.00 to 0.49, one trial, 2938 participants, low quality evidence). Personal protection using insecticide treated clothing was evaluated by two RCTs in soldiers, but the trials were underpowered to reliably detect effects on the incidence of CL (RR 0.40, 95% CI 0.13 to 1.20, two trials, 558 participants, low quality evidence). Visceral leishmaniasis In a single RCT of ITNs versus no intervention from India and Nepal, the incidence of VL was low in both groups and no difference was detected (RR 0.99, 95% CI 0.46 to 2.15, one trial, 19,810 participants, moderate quality evidence). Two trials from Brazil evaluated the effects of culling infected dogs compared to no intervention or IRS. Although they report a reduction in seroconversion over 18 months follow-up, they did not measure or report effects on clinical disease. Using insecticides to reduce phlebotomine sandfly numbers may be effective at reducing the incidence of CL, but there is insufficient evidence from trials to know whether it is better to spray the internal walls of houses or to treat bednets, curtains, bedsheets or clothing.

This review summarises trials evaluating different measures to prevent leishmaniasis. After searching for relevant trials up to January 2015, we included 14 randomized controlled trials. What is vector and reservoir control and how might they prevent leishmaniasis? Leishmaniasis is a group of infectious diseases caused by Leishmania parasites, which are transmitted between humans and animals by the bite of infected phlebotomine sandflies. There are two main clinical diseases: cutaneous leishmaniasis (CL), where parasites infect the skin, and visceral leishmaniasis (VL), where they infect the internal organs. Leishmaniasis could be prevented by reducing human contact with infected phlebotomine sandflies (the vector), or by reducing the number of infected animals (the reservoir). What the research says? Cutaneous leishmaniasis Using insecticides to reduce the number of sandflies may be effective at reducing the number of new cases of cutaneous leishmaniasis (low quality evidence). However, there is not enough evidence to know whether it is better to use insecticides to spray the internal walls of houses, or use insecticide treated bednets, bedsheets, or curtains. Personal protection using insecticide treated clothing was also evaluated in two small trials in soldiers, but the trials were too small to know whether this was effective (low quality evidence). Visceral leishmaniasis Insecticide treated nets may not be effective at preventing visceral leishmaniasis but this has only been tested in a single trial from India and Nepal (low quality evidence). Although culling dogs is sometimes discussed as a potential way to reduce visceral leishmaniasis, this has not been tested in trials measuring clinical disease.

10.1002/14651858.CD008736.pub2

cochrane-simplification-train-3559

cochrane-simplification-train-3559

The search resulted in 524 potentially relevant articles. Five eligible randomized controlled trials (RCTs) were identified (305 women). Trials using oral tablets, transdermal patches and implants were identified. No trial used gels. One small cross-over trial (11 women, effective sample size 22 women considering cross-over trials) compared oral luteal-phase oestrogen versus placebo. Data were very low quality and unsuitable for analysis, but study authors reported that the intervention was ineffective and might aggravate the symptoms of PMS. They also reported that there were no adverse events. Three studies compared continuous oestrogen with progestogen versus placebo (with or without progestogen). These trials were of reasonable quality, although with a high risk of attrition bias and an unclear risk of bias due to potential carry-over effects in two cross-over trials. Continuous oestrogen had a small to moderate positive effect on global symptom scores (SMD −0.34, 95% CI −0.59 to −0.10, P = 0.005, 3 RCTs, 158 women, effective sample size 267 women, I² = 63%, very low quality evidence). The evidence was too imprecise to determine if the groups differed in withdrawal rates due to adverse effects (RR 0.64, 95% CI 0.26 to 1.58, P = 0.33, 3 RCTs, 196 women, effective sample size 284 women, I² = 0%, very low quality evidence). Similarly, the evidence was very imprecise in measures of specific adverse events, with large uncertainties around the true value of the relative risk. None of the studies reported on long-term risks such as endometrial cancer or breast cancer. One study compared patch dosage (100 vs 200 µg oestrogen, with progestogen in both arms) and had a high risk of performance bias, detection bias and attrition bias. The study did not find evidence that dosage affects global symptoms but there was much uncertainty around the effect estimate (SMD −1.55, 95% CI −8.88 to 5.78, P = 0.68, 1 RCT, 98 women, very low quality evidence). The evidence on rates of withdrawal for adverse events was too imprecise to draw any conclusions (RR 0.70, 95% CI 0.34 to 1.46, P = 0.34, 1 RCT, 107 women, low-quality evidence). However, it appeared that the 100 µg dose might be associated with a lower overall risk of adverse events attributed to oestrogen (RR 0.51, 95% Cl 0.26 to 0.99, P = 0.05, 1 RCT, 107 women, very low quality evidence) with a large uncertainty around the effect estimate. The overall quality of the evidence for all comparisons was very low, mainly due to risk of bias (specifically attrition), imprecision, and statistical and clinical heterogeneity. We found very low quality evidence to support the effectiveness of continuous oestrogen (transdermal patches or subcutaneous implants) plus progestogen, with a small to moderate effect size. We found very low quality evidence from a study based on 11 women to suggest that luteal-phase oral unopposed oestrogen is probably ineffective and possibly detrimental for controlling the symptoms of PMS. A comparison between 200 µg and 100 µg doses of continuous oestrogen was inconclusive with regard to effectiveness, but suggested that the lower dose was less likely to cause side effects. Uncertainty remains regarding safety, as the identified studies were too small to provide definite answers. Moreover, no included trial addressed adverse effects that might occur beyond the typical trial duration of 2-8 months. This suggests the choice of oestrogen dose and mode of administration could be based on an individual woman’s preference and modified according to the effectiveness and tolerability of the chosen regimen.

The review identified 524 potentially relevant articles. Only five randomized controlled trials met our inclusion criteria, and these compared oestrogen with placebo in a total of 305 women who were clinically diagnosed with PMS. We found very low quality evidence to suggest that oral unopposed oestrogen given in the luteal phase of the menstrual cycle is probably ineffective for controlling the symptoms of PMS and may even make them worse. There was very low quality evidence to support the effectiveness of continuous oestrogen (in the form of transdermal patches or subcutaneous implants) plus progestogen, with a small to moderate effect size. A comparison between 200 microgram and 100 microgram doses of continuous oestrogen was inconclusive with regard to effectiveness but suggested that the lower dose was less likely to cause side effects. Uncertainty remains regarding safety, as the identified studies were too small to provide definite answers. Moreover, none of the included trials addressed adverse effects that might occur beyond the typical trial duration of 2 to 8 months. This suggests the choice of oestrogen dose and mode of administration could be based on an individual woman’s preference and modified according to the effectiveness and tolerability of the chosen regimen. The overall quality of the evidence for all comparisons was graded as very low, mainly due to risk of bias in the included studies, imprecision (due to small sample sizes) and differences between the studies.

10.1002/14651858.CD010503.pub2

cochrane-simplification-train-3560

cochrane-simplification-train-3560

We included six small trials involving 244 adults with olecranon fractures. Of these, four were RCTs and two were quasi-RCTs; both of were at high risk of selection bias. All six trials were at high risk of performance bias, reflecting lack of blinding, and four trials were at high risk of detection bias. The quality of the evidence for most outcomes was generally very low because of limitations in study design and implementation, and either imprecision of the results or inadequate outcome measures. Thus, we are very uncertain about the estimates of effect. One trial (41 participants) comparing plate fixation with standard tension band wiring provided very low quality evidence at 16 to 86 weeks' follow-up of a better clinical outcome after plate fixation (good outcome (little pain or loss of elbow motion): 19/22 versus 9/19, risk ratio (RR) 1.82 favouring plate fixation, 95% confidence interval (CI) 1.10 to 3.01). There was very low quality evidence of less symptomatic prominent metalwork after plate fixation (1/22 versus 8/19; RR 0.11, 95% CI 0.01 to 0.79). The results for other adverse effects (infection and delayed or non-union) were inconclusive. Evidence is pending from a newly (September 2014) completed trial (67 participants) making the same comparison. Four trials compared four different modified techniques of tension band wiring (i.e. additional intramedullary screw fixation, biodegradable pins, Netz pins and cable pin system) versus standard tension band wiring. There was very low quality evidence of little difference at six to 14 months in function assessed by a non-validated scoring tool from the addition of an intramedullary screw. However, there were fewer cases of metalwork prominence in the intramedullary screw group (1/15 versus 8/15; RR 2.00, 95% CI 1.15 to 3.49; one trial; 30 participants). There was very low quality evidence from one trial (25 participants) of little difference in subjectively or objectively assessed good outcome at a mean of 20 months between tension band wiring with biodegradable implants versus metal implants. There were no adverse events, either non-union or sinus or fluid accumulation, reported. All 10 participants in the metalwork group had an extra operation to remove their metalwork at one year. One trial, which did not report on function or pain, provided very low quality evidence of lower rates of metalwork for any reason or for symptoms after Netz pin tension band wiring compared with standard tension band wiring (11/21 with Netz pin versus 17/25 with standard tension band wiring; RR 0.77, 95% CI 0.47 to 1.26; 46 participants); this evidence also supports the possibility of higher rates of metalwork removal for Netz pins. Two intra-operative complications occurred in the Netz pin group. The fourth trial, which compared the cable pin system with standard procedure, found low quality evidence that cable pin improved functional outcome at a mean of 21 months (Mayo Elbow Performance Score (MEPS), range 0 to 100: best outcome: mean difference (MD) 7.89 favouring cable pin, 95% CI 3.14 to 12.64; one trial; 62 participants). It also found low quality evidence of fewer postoperative complications in the cable pin group (1/30 with cable pin system versus 7/32 standard tension band wiring; RR 0.15, 95% CI 0.02 to 1.17), although the evidence did not rule out the converse. One trial provided very low quality evidence of similar patient-reported function using the Disabilities of the Arm, Shoulder and Hand questionnaire (0 to 100: worst function) at two or more years after fixation using a novel olecranon memory connector (OMC) compared with locking plate fixation (MD -0.70 favouring OMC, 95% CI -4.20 to 2.80; 40 participants). The only adverse event was a superficial infection in the locking plate group. There is insufficient evidence to draw robust conclusions on the relative effects of the surgical interventions evaluated by the included trials. Further evidence, including patient-reported data, on the relative effects of plate versus tension band wiring is already pending from one recently completed RCT. Further RCTs, using good quality methods and reporting validated patient-reported measures of function, pain and activities of daily living at set follow-ups, are needed, including checking positive findings such as those relating to the use of an intramedullary screw and the cable pin system. Such trials should also include the systematic assessment of complications, further treatment including routine removal of metalwork and use of resources.

All six trials were small and had weaknesses that could affect the reliability of their results. We judged the overall quality of the evidence available for each comparison as either low or very low. One trial compared the use of plate fixation with tension band wiring. It found that more people had pain-free elbow motion after plate fixation and fewer people had discomfort from metalwork prominence, which is a well-known problem with wire fixation where the metal wiring on the surface of the bone just under the skin causes pain, discomfort and other problems. Four trials compared different ways of wiring the fracture. Two trials found very little clear evidence of any differences between them. One trial found that adding an intramedullary screw (this is a screw that was inserted through the bone and along the central bone canal) to standard tension band wiring reduced the risk of the metalwork under the skin being prominent. Another trial found that the cable pin system improved function and resulted in fewer complications compared with standard tension band wiring. Finally, one trial compared a new method of fixation using a titanium-nickel device that once implanted takes the shape of the olecranon with locking plate fixation. It found no clear evidence of differences between the techniques in patient-reported function and complications (the only complication was a superficial infection). Currently, there is not enough evidence to determine the best treatment for these fractures with confidence. Further high quality research is needed, which is likely to have an important impact on our confidence in the estimates of the effects and will likely change the estimates.

10.1002/14651858.CD010144.pub2

cochrane-simplification-train-3561

cochrane-simplification-train-3561

Thirty-four trials (3230 participants) were included. Meta-analysis showed that the mean change in urinary sodium (reduced salt vs usual salt) was -75 mmol/24-h (equivalent to a reduction of 4.4 g/d salt), the mean change in BP was -4.18 mmHg (95% CI: -5.18 to -3.18, I2=75%) for systolic and -2.06 mmHg (95% CI: -2.67 to -1.45, I2=68%) for diastolic BP. Meta-regression showed that age, ethnic group, BP status (hypertensive or normotensive) and the change in 24-h urinary sodium were all significantly associated with the fall in systolic BP, explaining 68% of the variance between studies. A 100 mmol reduction in 24 hour urinary sodium (6 g/day salt) was associated with a fall in systolic BP of 5.8 mmHg (95%CI: 2.5 to 9.2, P=0.001) after adjusting for age, ethnic group and BP status. For diastolic BP, age, ethnic group, BP status and the change in 24-h urinary sodium explained 41% of the variance between studies. Meta-analysis by subgroup showed that, in hypertensives, the mean effect was -5.39 mmHg (95% CI: -6.62 to -4.15, I2=61%) for systolic and -2.82 mmHg (95% CI: -3.54 to -2.11, I2=52%) for diastolic BP. In normotensives, the mean effect was -2.42 mmHg (95% CI: -3.56 to -1.29, I2=66%) for systolic and -1.00 mmHg (95% CI: -1.85 to -0.15, I2=66%) for diastolic BP. Further subgroup analysis showed that the decrease in systolic BP was significant in both whites and blacks, men and women. Meta-analysis of hormone and lipid data showed that the mean effect was 0.26 ng/ml/hr (95% CI: 0.17 to 0.36, I2=70%) for plasma renin activity, 73.20 pmol/l (95% CI: 44.92 to 101.48, I2=62%) for aldosterone, 31.67 pg/ml (95% CI: 6.57 to 56.77, I2=5%) for noradrenaline, 6.70 pg/ml (95% CI: -0.25 to 13.64, I2=12%) for adrenaline, 0.05 mmol/l (95% CI: -0.02 to 0.11, I2=0%) for cholesterol, 0.05 mmol/l (95% CI: -0.01 to 0.12, I2=0%) for LDL, -0.02 mmol/l (95% CI: -0.06 to 0.01, I2=16%) for HDL, and 0.04 mmol/l (95% CI: -0.02 to 0.09, I2=0%) for triglycerides. A modest reduction in salt intake for 4 or more weeks causes significant and, from a population viewpoint, important falls in BP in both hypertensive and normotensive individuals, irrespective of sex and ethnic group. With salt reduction, there is a small physiological increase in plasma renin activity, aldosterone and noradrenaline. There is no significant change in lipid levels. These results provide further strong support for a reduction in population salt intake. This will likely lower population BP and, thereby, reduce cardiovascular disease. Additionally, our analysis demonstrates a significant association between the reduction in 24-h urinary sodium and the fall in systolic BP, indicating the greater the reduction in salt intake, the greater the fall in systolic BP. The current recommendations to reduce salt intake from 9-12 to 5-6 g/d will have a major effect on BP, but are not ideal. A further reduction to 3 g/d will have a greater effect and should become the long term target for population salt intake.

Our pooled analysis of randomised trials of 4 weeks or more in duration shows that such a reduction in salt intake lowers blood pressure both in individuals with raised blood pressure and in those with normal blood pressure. The fall in blood pressure is shown in both whites and blacks, men and women. Additionally, our results show that a longer-term modest reduction in salt intake has no adverse effect on hormone and lipid levels. These findings provide further strong support for a reduction in population salt intake. This will likely lower population blood pressure and reduce strokes, heart attacks and heart failure. Furthermore, our results are consistent with the fact that the lower the salt intake, the lower the blood pressure. The current recommendations to reduce salt intake to 5-6 grams per day will lower blood pressure, but a further reduction to 3 grams per day will lower blood pressure more. Therefore, 3 grams per day should become the long-term target for population salt intake.

10.1002/14651858.CD004937.pub2

cochrane-simplification-train-3562

cochrane-simplification-train-3562

Investigators included 6201 participants in the 51 included trials. Twenty studies included only children, two included only preschool children and ten only adolescents; all others included both children and adolescents. Participants were exposed to sexual abuse in 12 trials, to war or community violence in ten, to physical trauma and natural disaster in six each and to interpersonal violence in three; participants had suffered a life-threatening illness and had been physically abused or maltreated in one trial each. Participants in remaining trials were exposed to a range of traumas. Most trials compared a psychological therapy with a control such as treatment as usual, wait list or no treatment. Seventeen trials used cognitive-behavioural therapy (CBT); four used family therapy; three required debriefing; two trials each used eye movement desensitisation and reprocessing (EMDR), narrative therapy, psychoeducation and supportive therapy; and one trial each provided exposure and CBT plus narrative therapy. Eight trials compared CBT with supportive therapy, two compared CBT with EMDR and one trial each compared CBT with psychodynamic therapy, exposure plus supportive therapy with supportive therapy alone and narrative therapy plus CBT versus CBT alone. Four trials compared individual delivery of psychological therapy to a group model of the same therapy, and one compared CBT for children versus CBT for both mothers and children. The likelihood of being diagnosed with PTSD in children and adolescents who received a psychological therapy was significantly reduced compared to those who received no treatment, treatment as usual or were on a waiting list for up to a month following treatment (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.34 to 0.77; number needed to treat for an additional beneficial outcome (NNTB) 6.25, 95% CI 3.70 to 16.67; five studies; 874 participants). However the overall quality of evidence for the diagnosis of PTSD was rated as very low. PTSD symptoms were also significantly reduced for a month after therapy (standardised mean difference (SMD) -0.42, 95% CI -0.61 to -0.24; 15 studies; 2051 participants) and the quality of evidence was rated as low. These effects of psychological therapies were not apparent over the longer term. CBT was found to be no more or less effective than EMDR and supportive therapy in reducing diagnosis of PTSD in the short term (OR 0.74, 95% CI 0.29 to 1.91; 2 studies; 160 participants), however this was considered very low quality evidence. For reduction of PTSD symptoms in the short term, there was a small effect favouring CBT over EMDR, play therapy and supportive therapies (SMD -0.24, 95% CI -0.42 to -0.05; 7 studies; 466 participants). The quality of evidence for this outcome was rated as moderate. We did not identify any studies that compared pharmacological therapies with psychological therapies. The meta-analyses in this review provide some evidence for the effectiveness of psychological therapies in prevention of PTSD and reduction of symptoms in children and adolescents exposed to trauma for up to a month. However, our confidence in these findings is limited by the quality of the included studies and by substantial heterogeneity between studies. Much more evidence is needed to demonstrate the relative effectiveness of different psychological therapies for children exposed to trauma, particularly over the longer term. High-quality studies should be conducted to compare these therapies.

Children and adolescents receiving psychological therapies were less likely to be diagnosed with PTSD and had fewer symptoms of PTSD up to a month after treatment compared with those who received no treatment, treatment as usual or were on a waiting list. Our confidence in these findings is limited as the overall quality of evidence was very low to low. There was no evidence for the effectiveness of psychological therapies beyond one month. There was moderate quality evidence that cognitive-behavioural therapy (CBT) might be more effective in reducing symptoms of PTSD compared to other psychological therapies for up to a month. Adverse effects were not reported. There were no studies which compared psychological therapies to drug treatments. Researchers should conduct high-quality trials to further evaluate the effectiveness of psychological therapies for children and adolescents exposed to trauma. These trials should be designed to ensure that participants and their families are not aware of whether they are receiving psychological therapy, particularly when measures are completed by participants or their parents. In addition, efforts should be made to ensure high rates of follow-up beyond one month after completion of therapy. In addition, studies should compare different types of psychological therapy to give a better indication of whether children and adolescents exposed to different types of trauma are more or less likely to respond to these therapies.

10.1002/14651858.CD012371

cochrane-simplification-train-3563

cochrane-simplification-train-3563

In the initial review, we included one ITS study that evaluated a targeted educational intervention aimed at reducing the incidence of wrong-site tooth extractions. The intervention included examination of previous cases of wrong-site tooth extractions, educational intervention including a presentation of cases of erroneous extractions, explanation of relevant clinical guidelines and feedback by an instructor. Data were reported from all patients on the surveillance system of a University Medical centre in Taiwan with a total of 24,406 tooth extractions before the intervention and 28,084 tooth extractions after the intervention. We re-analysed the data using the Prais-Winsten time series and the change in level for annual number of mishaps was statistically significant at -4.52 (95% confidence interval (CI) -6.83 to -2.217) (standard error (SE) 0.5380). The change in slope was statistically significant at -1.16 (95% CI -2.22 to -0.10) (SE 0.2472; P < 0.05). This update includes an additional study reporting on the incidence of neurological WSS at a university hospital both before and after the Universal Protocol’s implementation. A total of 22,743 patients undergoing neurosurgical procedures at the University of Illionois College of Medicine at Peoria, Illinois, United States of America were reported. Of these, 7286 patients were reported before the intervention and 15,456 patients were reported after the intervention. The authors found a significant difference (P < 0.001) in the incidence of WSS between the before period, 1999 to 2004, and the after period, 2005 to 2011.  Similarly, data were re-analysed using Prais-Winsten regression to correct for autocorrelation. As the incidences were reported by year only and the intervention occurred in July 2004, the intervention year 2004 was excluded from the analysis. The change in level at the point the intervention was introduced was not statistically significant at -0.078 percentage points (pp) (95% CI -0.176 pp to 0.02 pp; SE 0.042; P = 0.103). The change in slope was statistically significant at 0.031 (95% CI 0.004 to 0.058; SE 0.012; P < 0.05). The findings of this update added one additional ITS study to the previous review which contained one ITS study. The original review suggested that the use of a specific educational intervention in the context of a dental outpatient setting, which targets junior dental staff using a training session that included cases of wrong-site surgery, presentation of clinical guidelines and feedback by an instructor, was associated with a reduction in the incidence of wrong-site tooth extractions. The additional study in this update evaluated the annual incidence rates of wrong-site surgery in a neurosurgical population before and after the implementation of the Universal Protocol. The data suggested a strong downward trend in the incidence of wrong-site surgery prior to the intervention with the incidence rate approaching zero. The effect of the intervention in these studies however remains unclear, as data reflect only two small low-quality studies in very specific population groups.

This updated review contains two interrupted-time-series (ITS) studies (studies in which data are collected at multiple time points before and after an intervention), one from the original review, which evaluated a targeted educational intervention aimed at reducing the incidence of wrong-site surgery, and which was found to reduce its incidence. An additional study evaluated the incidence of wrong-site surgery before and after the introduction of the Universal Protocol, however the relevance of these findings regarding the impact of the intervention is unclear given that prior to its introduction, the incidence was decreasing due to other unclear factors. Overall, this review now contains two studies, of relatively low quality evidence, on very specific populations and their generalisability to a larger audience is low.

10.1002/14651858.CD009404.pub3

cochrane-simplification-train-3564

cochrane-simplification-train-3564

Five studies (182 children) met the inclusion criteria, and four contributed data to at least one meta-analysis. The included studies were overall at low risk of bias, but our confidence in the evidence was generally low, mainly due to the small sample sizes. Treatment with IV MgSO4 reduced the odds of admission to hospital by 68% (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14 to 0.74; children = 115; studies = 3; I2 = 63%). This result was based on data from just three studies including 115 children. Meta-analysis for the secondary outcomes was extremely limited by paucity of data. We performed meta-analysis for the outcome 'return to the emergency department within 48 hours', which showed a very imprecise effect estimate that was not statistically significant (OR 0.40, 95% CI 0.02 to 10.30; children = 85; studies = 2; I2 = 0%). Side effects and adverse events were not consistently reported and meta-analysis was not possible, however few side effects or adverse events were reported. IV MgSO4 may reduce the need for hospital admission in children presenting to the ED with moderate to severe exacerbations of asthma, but the evidence is extremely limited by the number and size of studies. Few side effects of the treatment were reported, but the data were extremely limited.

We found five studies in children that compared an infusion of MgSO4 to a placebo infusion when other treatments had not relieved the attack (usually inhaled bronchodilators, steroids, and sometimes oxygen). These five studies included a total of 182 children. Only three of the studies reported the outcome we were most interested in, which was the need to be admitted to hospital. The studies were published between 1996 and 2000; these were the most current studies we could find when we searched in February 2016. Fewer children who had an infusion of MgSO4 needed to be admitted to hospital compared with placebo. In fact, for every five children treated with the MgSO4, one admission to hospital was prevented. However, the included studies were small, with only 115 children in the main analysis, and the results did vary, so we cannot be absolutely sure of the benefits and harms. As there were so few studies, we also could not tell whether the reduction in hospital admissions was associated with age, severity of the asthma exacerbation, or whether it made a difference what other treatments were given. There were no reports of harm when the children received MgSO4. The review therefore supports the use of MgSO4 in children, however it must be noted that the evidence for its use is very weak.

10.1002/14651858.CD011050.pub2

cochrane-simplification-train-3565

cochrane-simplification-train-3565

We included 12 trials (576 participants); 11 had two arms and one had three arms. All assessed topical agents, none looked at systemic antibiotics. The included trials assessed the following antimicrobial agents: povidone iodine, cadexomer iodine, gentian violet, lysozyme, silver dressings, honey, pine resin, polyhexanide, silver sulfadiazine, and nitrofurazone with ethoxy-diaminoacridine. Comparators included a range of other dressings and ointments without antimicrobial properties and alternative antimicrobials. Each comparison had only one trial, participant numbers were low and follow-up times short. The evidence varied from moderate to very low quality. Six trials reported the primary outcome of wound healing. All except one compared an antiseptic with a non-antimicrobial comparator. There was some moderate and low quality evidence that fewer ulcers may heal in the short term when treated with povidone iodine compared with non-antimicrobial alternatives (protease-modulating dressings (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.62 to 0.98) and hydrogel (RR 0.64, 95% CI 0.43 to 0.97)); and no clear difference between povidone iodine and a third non-antimicrobial treatment (hydrocolloid) (low quality evidence). Pine resin salve may heal more pressure ulcers than hydrocolloid (RR 2.83, 95% CI 1.14 to 7.05) (low quality evidence). There is no clear difference between cadexomer iodine and standard care, and between honey and a combined antiseptic and antibiotic treatment (very low quality evidence). Six trials reported adverse events (primary safety outcome). Four reported no adverse events; there was very low quality evidence from one showing no clear evidence of a difference between cadexomer iodine and standard care; in one trial it was not clear whether data were appropriately reported. There was limited reporting of secondary outcomes. The five trials that reported change in wound size as a continuous outcome did not report any clear evidence favouring any particular antiseptic/anti-microbial treatments. For bacterial resistance, one trial found some evidence of more MRSA eradication in participants with ulcer treated with a polyhexanide dressing compared with a polyhexanide swab (RR 1.48, 95% CI 1.02 to 2.13); patients in the dressing group also reported less pain (MD −2.03, 95% CI −2.66 to −1.40). There was no clear evidence of a difference between interventions in infection resolution in three other comparisons. Evidence for secondary outcomes varied from moderate to very low quality; where no GRADE assessment was possible we identified substantial limitations which an assessment would have taken into account. The relative effects of systemic and topical antimicrobial treatments on pressure ulcers are not clear. Where differences in wound healing were found, these sometimes favoured the comparator treatment without antimicrobial properties. The trials are small, clinically heterogenous, generally of short duration, and at high or unclear risk of bias. The quality of the evidence ranges from moderate to very low; evidence on all comparisons was subject to some limitations.

In October 2015 we searched for as many studies as we could find that were randomised controlled trials and compared the use of an antibiotic or antiseptic with other treatments for pressure ulcers. We found 12 trials involving a total of 576 participants. Most study participants were older people in hospital. Most ulcers were not infected at the start of the trials. The different treatments assessed included povidone iodine, cadexomer iodine, gentian violet, lysozyme, silver dressings, honey, pine resin, silver sulfadiazine, polyhexanide and a combination of nitrofurazone and ethoxy-diaminoacridine. Silver sulfadiazine and nitrofurazone are topical (locally acting) antibiotics while the other treatments are antiseptics. No trials looked at systemic (acting across the whole body) antibiotics. The treatments were compared with each other or to treatments without antimicrobial qualities. Most evidence on wound healing came from trials comparing antiseptics to treatments without antimicrobial qualities. There was no consistent evidence of a benefit to using any particular antimicrobial treatment for pressure ulcers. However, there was some limited evidence that more ulcers healed when treated with some types of alternative dressings without antimicrobial properties than when treated with povidone iodine. All the studies had low numbers of participants, and in some cases these numbers were very small. Many studies did not report important information about how they were carried out so it was difficult to tell whether the results presented were likely to be true. More, better quality, research is needed to determine the effects of antimicrobial treatments on pressure ulcers.

10.1002/14651858.CD011586.pub2

cochrane-simplification-train-3566

cochrane-simplification-train-3566

Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence but all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome. No significant effect of any of the treatments was seen compared to placebo. Immediate side effects were not found to be significantly different from placebo in the two trials where this information was reported. We considered the quality of evidence to be low to very low as all of the trials were at risk of bias and all had low participant numbers. There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.

We found three trials set in Jamaica, Nigeria and the UK involving 102 people. In the trials, four different drug treatments (stilboestrol, sildenafil, ephedrine and etilefrine) were compared to placebo. The trials all looked at whether the treatments reduced how often attacks of priapism occurred. There was no difference between any of the treatments compared to placebo. Due to lack of evidence, we are not able to conclude the best treatment of priapism in sickle cell disease. More research is needed. We considered the quality of evidence to be low to very low as all of the trials were at risk of bias and all had low participant numbers.

10.1002/14651858.CD004198.pub3

cochrane-simplification-train-3567

cochrane-simplification-train-3567

Ten studies (6 randomised controlled trials and 4 prospective cohort studies, involving 955 participants) met the inclusion criteria for the review. We considered 7 of the 10 studies to be at high risk of bias in at least one of the domains we assessed. Nine studies compared an opioid antagonist-adrenergic agonist combination versus a treatment regimen based primarily on an alpha2-adrenergic agonist (clonidine or lofexidine). Other comparisons (placebo, tapered doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. This review therefore focuses on the nine studies comparing an opioid antagonist (naltrexone or naloxone) plus clonidine or lofexidine versus treatment primarily based on clonidine or lofexidine. Five studies took place in an inpatient setting, two studies were in outpatients with day care, two used day care only for the first day of opioid antagonist administration, and one study described the setting as outpatient without indicating the level of care provided. The included studies were heterogeneous in terms of the type of opioid antagonist treatment regimen, the comparator, the outcome measures assessed, and the means of assessing outcomes. As a result, the validity of any estimates of overall effect is doubtful, therefore we did not calculate pooled results for any of the analyses. The quality of the evidence for treatment with an opioid antagonist-adrenergic agonist combination versus an alpha2-adrenergic agonist is very low. Two studies reported data on peak withdrawal severity, and four studies reported data on the average severity over the period of withdrawal. Peak withdrawal induced by opioid antagonists in combination with an adrenergic agonist appears to be more severe than withdrawal managed with clonidine or lofexidine alone, but the average severity over the withdrawal period is less. In some situations antagonist-induced withdrawal may be associated with significantly higher rates of treatment completion compared to withdrawal managed with adrenergic agonists. However, this result was not consistent across studies, and the extent of any benefit is highly uncertain. We could not extract any data on the occurrence of adverse events, but two studies reported delirium or confusion following the first dose of naltrexone. Delirium may be more likely with higher initial doses and with naltrexone rather than naloxone (which has a shorter half-life), but we could not confirm this from the available evidence. Insufficient data were available to make any conclusions on the best duration of treatment. Using opioid antagonists plus alpha2-adrenergic agonists is a feasible approach for managing opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist. A high level of monitoring and support is desirable for several hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium. Using opioid antagonists to induce and accelerate opioid withdrawal is not currently an active area of research or clinical practice, and the research community should give greater priority to investigating approaches, such as those based on buprenorphine, that facilitate the transition to sustained-release preparations of naltrexone.

We identified 10 studies, including six randomised controlled trials (where people are randomly put into one of two or more treatment groups) and four prospective cohort studies (where participants could choose which treatment they received) involving 955 opioid-dependent participants. Four of the studies took place in the UK, three in the USA, two in Italy and one in Australia. Nine of the 10 studies compared treatment with an opioid antagonist (naltrexone or naloxone) plus an adrenergic agonist (clonidine or lofexidine) versus a regimen based on clonidine or lofexidine alone. Other comparisons (placebo, reducing doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. Four studies received some financial support from a pharmaceutical company. We are uncertain whether peak withdrawal induced by opioid antagonists plus clonidine or lofexidine is more severe than withdrawal managed with clonidine or lofexidine alone, or whether the average severity over the withdrawal period is less, as the certainty of the evidence is very low. Clinicians should warn people of the possibility of delirium in the first day of administration of naltrexone, particularly with higher doses (> 25 mg). People should also know that withdrawal will be moderately severe and that symptoms such as muscle aches, vomiting and diarrhoea, and insomnia are likely to persist despite medication. The studies included in this review were diverse and generally of very low quality. As a result there is considerable uncertainty about the value of approaches using opioid antagonists to induce opioid withdrawal as a means of managing withdrawal from opioid dependence.

10.1002/14651858.CD002021.pub4