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cochrane-simplification-train-3300

cochrane-simplification-train-3300

Twenty randomised controlled trials involving 1170 patients were included in this systematic review. The overall risk of bias in included trials was assessed as unclear, because concealment of allocation processes and blinding of outcome assessors were poorly described. Due to inconsistent outcome reporting, data from 17 included trials could be pooled for some endpoints only. Eight trials compared tramadol administration with placebo and five trials found that the need for rescue analgesia in the postoperative care unit (PACU) was reduced in children receiving tramadol (RR 0.40; 95% CI 0.20 to 0.78; low quality evidence). Only one trial investigated the number of patients with moderate to severe pain, but a non-validated pain scale was used (very low quality evidence). Four trials compared morphine with tramadol administration. There was no clear evidence of difference in the need for rescue analgesia in the PACU (RR 1.25; 95% CI 0.83 to 1.89; low quality evidence) with tramadol compared with morphine. No trials could be pooled for the outcome 'number of patients with moderate to severe pain'. Three trials were included for the comparison of tramadol with nalbuphine. There was no clear evidence for the need for rescue analgesia in the PACU (RR 0,63; 95% CI 0.16 to 2.45; low quality evidence). Only one trial reported the number of patients with moderate to severe pain, but used a non-validated pain scale (very low quality evidence). Two out of six included trials, which compared pethidine with tramadol, reported the number of children with a need for rescue analgesia within the PACU and showed no clear evidence (RR 0.93; 95% CI 0.43 to 2.02; very low quality evidence). Two trials reported the number of patients with moderate to severe pain and showed a lower RR in patients treated with tramadol (RR 0.64; 95% CI 0.36 to 1.16; low quality evidence). Only one trial was included, which compared tramadol with fentanyl, reporting the number of patients with the need for rescue analgesia (very low quality evidence). Generally, adverse events were poorly reported. Most data could be pooled for the comparison with placebo focusing on the RR for postoperative nausea and vomiting (PONV) in the postoperative care unit and 24 h postoperation. Children treated with tramadol, compared to placebo, did not show clear evidence of benefit for PONV in the postoperative care unit (RR 0.84; 95% CI 0.28 to 2.52; moderate quality evidence) and 24 h postoperation (RR 0.78; 95% CI 0.54 to 1.12; moderate quality evidence). The overall evidence regarding tramadol for postoperative pain in children is currently low or very low and should be interpreted with caution due to small studies and methodological problems (different validated and non-validated pain scales with different pain triggers, missing sample size calculations and missing intention-to-treat analysis). Nevertheless, we demonstrated that tramadol administration might provide appropriate analgesia when compared to placebo; this is based on results showing reduced rescue analgesia in children treated with tramadol compared to placebo. In contrast, the evidence regarding the comparison with other opioids (for example morphine) was uncertain. Adverse events were only poorly reported, so an accurate risk-benefit analysis was not possible.

Children experience pain after surgery (‘postoperative pain’) and according to recently published trials the management of this pain is of major concern. A combination of drugs may be the best way to treat postoperative pain, for example drugs called ‘opioids’, like morphine and codeine. However, there are concerns about severe side effects (adverse events) when using opioids. Tramadol is a weak opioid that is used worldwide to treat children with moderate to severe acute or chronic pain. Tramadol can be given to children before surgery to help reduce pain afterwards. It is believed that tramadol administration might be associated with a lower risk for respiratory or haemodynamic depression and might therefore be the ideal analgesic drug for children in the perioperative period. Our systematic review assessed the efficacy and adverse events of tramadol administration compared to placebo or other opioids. In July 2014 we found 20 small randomised controlled trials involving 1170 patients. These small trials had limited data but tramadol may be better than placebo. In five trials, mostly preschool children undergoing minor surgery (for example tonsillectomy) were treated with tramadol or placebo before the start of surgery. Children needed less rescue medication in the postoperative care unit when given tramadol, indicating better analgesia with tramadol. Due to the low amount of usable data, the evidence focusing on the comparison of tramadol with other opioids (for example morphine, nalbuphine, pethidine, fentanyl) is currently unclear. Adverse events were generally only poorly reported in the trials so that the side effects as a result of tramadol administration were not clear.

10.1002/14651858.CD009574.pub2

cochrane-simplification-train-3301

cochrane-simplification-train-3301

We included 11 randomised trials, involving 638 women. The overall risk of bias was judged to be unclear due to lack of methodological detail in the included studies. For the mother, there was no clear evidence of a difference between women in the exercise group and those in the control group for the risk of pre-eclampsia as the measure of hypertensive disorders of pregnancy (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.01 to 7.09; two RCTs, 48 women; low-quality evidence), birth by caesarean section (RR 0.86, 95% CI 0.63 to 1.16; five RCTs, 316 women; I2 = 0%; moderate-quality evidence), the risk of induction of labour (RR 1.38, 95% CI 0.71 to 2.68; one RCT, 40 women; low-quality evidence) or maternal body mass index at follow-up (postnatal weight retention or return to pre-pregnancy weight) (mean difference (MD) 0.11 kg/m2, 95% CI -1.04 to 1.26; three RCTs, 254 women; I2 = 0%; high-quality evidence). Development of type 2 diabetes, perineal trauma/tearing and postnatal depression were not reported as outcomes in the included studies. For the infant/child/adult, a single small (n = 19) trial reported no perinatal mortality (stillbirth and neonatal mortality) events in either the exercise intervention or control group (low-quality evidence). There was no clear evidence of a difference between groups for a mortality and morbidity composite (variously defined by trials, e.g. perinatal or infant death, shoulder dystocia, bone fracture or nerve palsy) (RR 0.56, 95% CI 0.12 to 2.61; two RCTs, 169 infants; I2 = 0%; moderate-quality evidence) or neonatal hypoglycaemia (RR 2.00, 95% CI 0.20 to 20.04; one RCT, 34 infants; low-quality evidence). None of the included trials pre-specified large-for-gestational age, adiposity (neonatal/infant, childhood or adulthood), diabetes (childhood or adulthood) or neurosensory disability (neonatal/infant) as trial outcomes. Other maternal outcomes of interest: exercise interventions were associated with both reduced fasting blood glucose concentrations (average standardised mean difference (SMD) -0.59, 95% CI -1.07 to -0.11; four RCTs, 363 women; I2 = 73%; T2 = 0.19) and a reduced postprandial blood glucose concentration compared with control interventions (average SMD -0.85, 95% CI -1.15 to -0.55; three RCTs, 344 women; I2 = 34%; T2 = 0.03). Short- and long-term outcomes of interest for this review were poorly reported. Current evidence is confounded by the large variety of exercise interventions. There was insufficient high-quality evidence to be able to determine any differences between exercise and control groups for our outcomes of interest. For the woman, both fasting and postprandial blood glucose concentrations were reduced compared with the control groups. There are currently insufficient data for us to determine if there are also benefits for the infant. The quality of the evidence in this review ranged from high to low quality and the main reason for downgrading was for risk of bias and imprecision (wide CIs, low event rates and small sample size). Development of type 2 diabetes, perineal trauma/tearing, postnatal depression, large-for-gestational age, adiposity (neonate/infant, childhood or adulthood), diabetes (childhood or adulthood) or neurosensory disability (neonate/infant) were not reported as outcomes in the included studies. Further research is required comparing different types of exercise interventions with control groups or with another exercise intervention that reports on both the short- and long-term outcomes (for both the mother and infant/child) as listed in this review.

We searched for evidence from randomised controlled trials in August 2016. We identified 11 trials that involved 638 pregnant women. They were conducted in middle-or high-income countries. We judged the overall risk of bias in the trials as unclear because of a lack of information about how the trials were conducted. Using GRADE, the quality of the evidence from the trials ranged from high to low quality. The main reasons for downgrading the quality were for risk of bias in the trials and imprecise effect sizes, low event rates and small numbers of participants. For the mothers, exercising did not appear to reduce the risk of pre-eclampsia as the measure of hypertensive disorders of pregnancy (two trials, 48 women, low-quality evidence), birth by caesarean section (five trials, 316 women, moderate-quality evidence), or the risk of induction of labour (one trial, 40 women, low-quality evidence). The mothers had similar body mass index at follow-up in the exercise and control groups (three trials, 254 women, high-quality evidence). Exercising was associated with lower fasting blood glucose levels (four trials) and blood glucose levels after a meal (three trials) but with variations in effect sizes between the different trials. The exercise programmes varied between trials as did their duration and whether or not they were supervised. None of the included trials reported on perineal trauma, postnatal depression or development of type 2 diabetes. For the babies, no deaths occurred around the time of birth in (one trial, 19 babies, low-quality evidence) and there was no evidence of any difference in the risk of ill-health (two trials, 169 babies, moderate-quality evidence) or low blood sugar levels (one trial, 34 babies, low-quality evidence). None of the trials reported on the number of large-for-gestational-age babies or babies that went on to develop diabetes in childhood or adulthood or neurosensory disability that became apparent during childhood. Although exercise appeared to be able to lower fasting blood sugar levels and sugar levels after a meal, we did not find any differences in other outcomes for pregnant women with GDM. The present evidence is insufficient to advise for or against women enrolling in exercise programmes. Even if exercise does not provide any benefit during pregnancy, this change in lifestyle may persist after birth and may help prevent the onset of type 2 diabetes and its long-term complications. Pregnant women with GDM who wish to enrol in an exercise programme may wish to discuss their choice with a health professional. Further research is needed comparing one exercise intervention with another (or with a control) and reporting on both the short- and long-term outcomes (for both the mother and infant/child/adult) as listed in this review.

10.1002/14651858.CD012202.pub2

cochrane-simplification-train-3302

cochrane-simplification-train-3302

The review included 19 studies randomising 1190 participants with carpal tunnel syndrome. Two studies compared splinting with no treatment, five compared different splint designs, one compared different splint-wearing regimens, seven compared splint delivered as a single intervention with another non-surgical intervention, and five compared splint delivered alongside other non-surgical interventions with another non-surgical intervention. Only three studies reported concealing the allocation sequence, and only one reported blinding of participants. Three studies measured the primary outcome, short-term overall improvement at three months or less. One low quality study with 80 wrists found that compared to no treatment, splints worn at night more than tripled the likelihood of reporting overall improvement at the end of four weeks of treatment (RR 3.86, 95% CI 2.29 to 6.51). However, the lack of patient blinding and unclear allocation concealment suggests this result should be interpreted with caution. A very low quality quasi-randomised trial with 90 wrists found that wearing a neutral splint more than doubled the likelihood of reporting 'a lot or complete relief' at the end of two weeks of treatment compared with an extension splint (RR 2.43, 95% CI 1.12 to 5.28). The third study which measured short-term overall improvement did not report outcome data separately per group. Nine studies measured adverse effects of splinting and all found either no or few participants reporting discomfort or swelling due to splinting; however, the precision of all RRs was very low. Differences between groups in the secondary outcomes - symptoms, function, and neurophysiologic parameters - were most commonly small with 95% CIs incorporating effects in either direction. Overall, there is limited evidence that a splint worn at night is more effective than no treatment in the short term, but there is insufficient evidence regarding the effectiveness and safety of one splint design or wearing regimen over others, and of splint over other non-surgical interventions for CTS. More research is needed on the long-term effects of this intervention for CTS.

We searched for study reports and found 19 randomised or quasi-randomised controlled trials including 1190 participants overall that assessed the safety and benefit of splinting for people with CTS. The risk of bias of studies was low in some studies and unclear or high in others. One low quality study suggests that splinting at night leads to more overall improvement in the short term when compared to no treatment, but we cannot say from the evidence whether one splint design or wearing regimen is more effective than another, nor can we say that splinting is more effective than other non-surgical interventions for CTS (for example exercises, oral steroids). Nine trials measured adverse effects of splinting and all found either no or few participants reported discomfort or swelling due to splinting. More research is needed to find out how effective and safe splinting is for people with carpal tunnel syndrome, particularly in the long term.

10.1002/14651858.CD010003

cochrane-simplification-train-3303

cochrane-simplification-train-3303

We included 51 trials (2920 participants, 18 trials of manipulation/mobilisation versus control; 34 trials of manipulation/mobilisation versus another treatment, 1 trial had two comparisons). Cervical manipulation versus inactive control:For subacute and chronic neck pain, a single manipulation (three trials, no meta-analysis, 154 participants, ranged from very low to low quality) relieved pain at immediate- but not short-term follow-up. Cervical manipulation versus another active treatment:For acute and chronic neck pain, multiple sessions of cervical manipulation (two trials, 446 participants, ranged from moderate to high quality) produced similar changes in pain, function, quality of life (QoL), global perceived effect (GPE) and patient satisfaction when compared with multiple sessions of cervical mobilisation at immediate-, short- and intermediate-term follow-up. For acute and subacute neck pain, multiple sessions of cervical manipulation were more effective than certain medications in improving pain and function at immediate- (one trial, 182 participants, moderate quality) and long-term follow-up (one trial, 181 participants, moderate quality). These findings are consistent for function at intermediate-term follow-up (one trial, 182 participants, moderate quality). For chronic CGH, multiple sessions of cervical manipulation (two trials, 125 participants, low quality) may be more effective than massage in improving pain and function at short/intermediate-term follow-up. Multiple sessions of cervical manipulation (one trial, 65 participants, very low quality) may be favoured over transcutaneous electrical nerve stimulation (TENS) for pain reduction at short-term follow-up. For acute neck pain, multiple sessions of cervical manipulation (one trial, 20 participants, very low quality) may be more effective than thoracic manipulation in improving pain and function at short/intermediate-term follow-up. Thoracic manipulation versus inactive control: Three trials (150 participants) using a single session were assessed at immediate-, short- and intermediate-term follow-up. At short-term follow-up, manipulation improved pain in participants with acute and subacute neck pain (five trials, 346 participants, moderate quality, pooled SMD -1.26, 95% confidence interval (CI) -1.86 to -0.66) and improved function (four trials, 258 participants, moderate quality, pooled SMD -1.40, 95% CI -2.24 to -0.55) in participants with acute and chronic neck pain. A funnel plot of these data suggests publication bias. These findings were consistent at intermediate follow-up for pain/function/quality of life (one trial, 111 participants, low quality). Thoracic manipulation versus another active treatment: No studies provided sufficient data for statistical analyses. A single session of thoracic manipulation (one trial, 100 participants, moderate quality) was comparable with thoracic mobilisation for pain relief at immediate-term follow-up for chronic neck pain. Mobilisation versus inactive control: Mobilisation as a stand-alone intervention (two trials, 57 participants, ranged from very low to low quality) may not reduce pain more than an inactive control. Mobilisation versus another active treatment:For acute and subacute neck pain, anterior-posterior mobilisation (one trial, 95 participants, very low quality) may favour pain reduction over rotatory or transverse mobilisations at immediate-term follow-up. For chronic CGH with temporomandibular joint (TMJ) dysfunction, multiple sessions of TMJ manual therapy (one trial, 38 participants, very low quality) may be more effective than cervical mobilisation in improving pain/function at immediate- and intermediate-term follow-up. For subacute and chronic neck pain, cervical mobilisation alone (four trials, 165 participants, ranged from low to very low quality) may not be different from ultrasound, TENS, acupuncture and massage in improving pain, function, QoL and participant satisfaction at immediate- and intermediate-term follow-up. Additionally, combining laser with manipulation may be superior to using manipulation or laser alone (one trial, 56 participants, very low quality). Although support can be found for use of thoracic manipulation versus control for neck pain, function and QoL, results for cervical manipulation and mobilisation versus control are few and diverse. Publication bias cannot be ruled out. Research designed to protect against various biases is needed. Findings suggest that manipulation and mobilisation present similar results for every outcome at immediate/short/intermediate-term follow-up. Multiple cervical manipulation sessions may provide better pain relief and functional improvement than certain medications at immediate/intermediate/long-term follow-up. Since the risk of rare but serious adverse events for manipulation exists, further high-quality research focusing on mobilisation and comparing mobilisation or manipulation versus other treatment options is needed to guide clinicians in their optimal treatment choices.

This updated review includes 51 trials: 18 trials contrasted manipulation or mobilisation against no treatment or pretend treatment; 34 trials compared manipulation or mobilisation against another treatment (electrotherapy, exercise, medication) and various techniques or dosages. [Note one trial included two comparison groups]. Although other reviews focusing on adverse events suggest that mobilisation is safe and manipulation may result in rare but serious side effects such as stroke, disc herniation or serious neurological deficits, our review noted temporary and benign side effects with both approaches; more than half of the included trials did not report on adverse effects. • Manipulation or mobilisation versus inactive treatment: For subacute/chronic neck pain, a single manipulation produced temporary pain relief. However, conflicting evidence was found at short-term follow-up for pain reduction with multiple sessions. At short-term and intermediate-term follow-up, multiple sessions of thoracic manipulation were favoured for pain reduction among participants with acute/subacute neck pain, and for functional improvement among those with acute to chronic neck pain. No additional pain relief was reported when thoracic mobilisation was used. • Manipulation or mobilisation versus another active treatment: Cervical manipulation produced changes in pain, function, quality of life, global perceived effect and patient satisfaction that were comparable with those attained with cervical mobilisation up to intermediate-term follow-up for patients with neck pain of any duration. Cervical manipulation for acute/subacute neck pain was more effective than varied combinations of analgesics, muscle relaxants and non-steroidal anti-inflammatory drugs for improving pain and function at up to long-term follow-up. For chronic cervicogenic headache, cervical manipulation provided greater benefit than light massage in improving pain and function at short-term and intermediate-term follow-up. For chronic CGH, cervical manipulation may be superior to transcutaneous electrical nerve stimulation (TENS) in improving pain at short-term follow-up. For acute neck pain, cervical manipulation may be more effective than thoracic manipulation in improving pain and function up to intermediate-term follow-up. Finally, for subacute and chronic neck pain, cervical mobilisation appeared similar to pulsed ultrasound, TENS, acupuncture and massage in improving pain, function, quality of life and patient satisfaction up to intermediate-term follow-up. However, combining laser with manipulation may be superior to using manipulation or laser alone. No high-quality evidence was found, so uncertainty about the effectiveness of mobilisation or manipulation for neck pain remains. Future research is likely to have an important impact on the effect estimate. Authors of this review encountered many challenges, for example, the number of participants in most trials was small, 80% (41/51) of the included studies were of low or very low quality and evidence on the optimum dosage requirement was limited.

10.1002/14651858.CD004249.pub4

cochrane-simplification-train-3304

cochrane-simplification-train-3304

We included 27 trials, 18 of which were conducted in the USA. Nineteen studies employed randomised controlled trial (RCT) designs. Fifteen trials tested strategies to implement healthy eating policies, practice or programs; six trials tested strategies targeting physical activity policies or practices; and three trials targeted tobacco policies or practices. Three trials targeted a combination of risk factors. None of the included trials sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. All trials examined multi-strategic implementation strategies and no two trials examined the same combinations of implementation strategies. The most common implementation strategies included educational materials, educational outreach and educational meetings. For all outcomes, the overall quality of evidence was very low and the risk of bias was high for the majority of trials for detection and performance bias. Among 13 trials reporting dichotomous implementation outcomes—the proportion of schools or school staff (e.g. classes) implementing a targeted policy or practice—the median unadjusted (improvement) effect sizes ranged from 8.5% to 66.6%. Of seven trials reporting the percentage of a practice, program or policy that had been implemented, the median unadjusted effect (improvement), relative to the control ranged from -8% to 43%. The effect, relative to control, reported in two trials assessing the impact of implementation strategies on the time per week teachers spent delivering targeted policies or practices ranged from 26.6 to 54.9 minutes per week. Among trials reporting other continuous implementation outcomes, findings were mixed. Four trials were conducted of strategies that sought to achieve implementation 'at scale', that is, across samples of at least 50 schools, of which improvements in implementation were reported in three trials. The impact of interventions on student health behaviour or weight status were mixed. Three of the eight trials with physical activity outcomes reported no significant improvements. Two trials reported reductions in tobacco use among intervention relative to control. Seven of nine trials reported no between-group differences on student overweight, obesity or adiposity. Positive improvements in child dietary intake were generally reported among trials reporting these outcomes. Three trials assessed the impact of implementation strategies on the attitudes of school staff and found mixed effects. Two trials specified in the study methods an assessment of potential unintended adverse effects, of which, they reported none. One trial reported implementation support did not significantly increase school revenue or expenses and another, conducted a formal economic evaluation, reporting the intervention to be cost-effective. Trial heterogeneity, and the lack of consistent terminology describing implementation strategies, were important limitations of the review. Given the very low quality of the available evidence, it is uncertain whether the strategies tested improve implementation of the targeted school-based policies or practices, student health behaviours, or the knowledge or attitudes of school staff. It is also uncertain if strategies to improve implementation are cost-effective or if they result in unintended adverse consequences. Further research is required to guide efforts to facilitate the translation of evidence into practice in this setting.

Study characteristics: We included 27 trials, 18 of which were conducted in the USA. Fifeteen trials tested strategies to implement healthy eating policies, practice or programs; six trials tested strategies targeting physical activity policies or practices; and three trials targeted tobacco policies or practices. Three trials targeted a combination of health behaviours. None of the included trials sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. The trials tested a range of implementation support strategies, including educational materials, educational meetings, the use of opinion leaders, external funding, local consensus processes, and tailored interventions. Search date: The evidence is current to 31 August 2016. Key results: It is uncertain whether the strategies tested improve implementation of the targeted school-based policies or practices, student health behaviours, or the knowledge or attitudes of school staff. It is also uncertain whether the strategies tested result in unintended adverse effects or whether they are cost-effective. Limitations: Trial heterogeneity, and the lack of consistent terminology describing implementation strategies were important limitations of the review. Quality of evidence: We rated the overall quality of evidence as very low for all outcomes that included trial-reported effects.

10.1002/14651858.CD011677.pub2

cochrane-simplification-train-3305

cochrane-simplification-train-3305

One study was included in the review. This multi-centre trial was based in five Australian hospitals and recruited 272 children with chronic cough. Children were randomly assigned to early (two weeks) or delayed (six weeks) referral to respiratory specialists who used a cough management pathway. When an intention-to-treat analysis was performed, clinical failure at six weeks post randomisation (defined as < 75% improvement in cough score, or total resolution for fewer than three consecutive days) was significantly less in the early pathway arm compared with the control arm (odds ratio (OR) 0.35, 95% confidence interval (CI) 0.21 to 0.58). These results indicate that one additional child will be cured for every five children treated via the cough pathway (number needed to treat for an additional beneficial outcome (NNTB) = 5, 95% CI 3 to 9) at six weeks. Cough-specific parent-reported quality of life scores were significantly better in the early-pathway group; the mean difference (MD) between groups was 0.60 (95% CI 0.19 to 1.01). Duration of cough post randomisation was significantly shorter in the intervention group (early-pathway arm) compared with the control group (delayed-pathway arm) (MD -2.70 weeks, 95% CI -4.26 to -1.14). Current evidence suggests that using a clinical algorithm for the management of children with chronic cough in hospital outpatient settings is more effective than providing wait-list care. Futher high-quality randomised controlled trials are needed to perform ongoing evaluation of cough management pathways in general practitioner and other primary care settings.

Only a single multi-centre study could be included in this review. Evidence is current to January 2014. This study was funded by the National Health and Medical Research Council of Australia. This study of 272 children in five Australian hospitals reported that those randomly assigned to earlier treatment according to a clinical pathway showed improved clinical outcomes (cough resolved earlier and quality of life was better) compared with those who were randomly assigned to later use of the pathway. No adverse events were reported. The quality of evidence was graded as moderate. Evidence is limited, as only one study could be included in this review. This study was unable to completely blind participants to the clinical pathway.

10.1002/14651858.CD006595.pub3

cochrane-simplification-train-3306

cochrane-simplification-train-3306

We included 75 systematic reviews of varied methodological quality. Reviews assessed interventions with diverse aims including support for behaviour change, risk minimisation and skills acquisition. No reviews aimed to promote systems-level consumer participation in medicines-related activities. Medicines adherence was the most frequently-reported outcome, but others such as knowledge, clinical and service-use outcomes were also reported. Adverse events were less commonly identified, while those associated with the interventions themselves, or costs, were rarely reported. Looking across reviews, for most outcomes, medicines self-monitoring and self-management programmes appear generally effective to improve medicines use, adherence, adverse events and clinical outcomes; and to reduce mortality in people self-managing antithrombotic therapy. However, some participants were unable to complete these interventions, suggesting they may not be suitable for everyone. Other promising interventions to improve adherence and other key medicines-use outcomes, which require further investigation to be more certain of their effects, include: · simplified dosing regimens: with positive effects on adherence; · interventions involving pharmacists in medicines management, such as medicines reviews (with positive effects on adherence and use, medicines problems and clinical outcomes) and pharmaceutical care services (consultation between pharmacist and patient to resolve medicines problems, develop a care plan and provide follow-up; with positive effects on adherence and knowledge). Several other strategies showed some positive effects, particularly relating to adherence, and other outcomes, but their effects were less consistent overall and so need further study. These included: · delayed antibiotic prescriptions: effective to decrease antibiotic use but with mixed effects on clinical outcomes, adverse effects and satisfaction; · practical strategies like reminders, cues and/or organisers, reminder packaging and material incentives: with positive, although somewhat mixed effects on adherence; · education delivered with self-management skills training, counselling, support, training or enhanced follow-up; information and counselling delivered together; or education/information as part of pharmacist-delivered packages of care: with positive effects on adherence, medicines use, clinical outcomes and knowledge, but with mixed effects in some studies; · financial incentives: with positive, but mixed, effects on adherence. Several strategies also showed promise in promoting immunisation uptake, but require further study to be more certain of their effects. These included organisational interventions; reminders and recall; financial incentives; home visits; free vaccination; lay health worker interventions; and facilitators working with physicians to promote immunisation uptake. Education and/or information strategies also showed some positive but even less consistent effects on immunisation uptake, and need further assessment of effectiveness and investigation of heterogeneity. There are many different potential pathways through which consumers' use of medicines could be targeted to improve outcomes, and simple interventions may be as effective as complex strategies. However, no single intervention assessed was effective to improve all medicines-use outcomes across all diseases, medicines, populations or settings. Even where interventions showed promise, the assembled evidence often only provided part of the picture: for example, simplified dosing regimens seem effective for improving adherence, but there is not yet sufficient information to identify an optimal regimen. In some instances interventions appear ineffective: for example, the evidence suggests that directly observed therapy may be generally ineffective for improving treatment completion, adherence or clinical outcomes. In other cases, interventions may have variable effects across outcomes. As an example, strategies providing information or education as single interventions appear ineffective to improve medicines adherence or clinical outcomes, but may be effective to improve knowledge; an important outcome for promoting consumers' informed medicines choices. Despite a doubling in the number of reviews included in this updated overview, uncertainty still exists about the effectiveness of many interventions, and the evidence on what works remains sparse for several populations, including children and young people, carers, and people with multimorbidity. This overview presents evidence from 75 reviews that have synthesised trials and other studies evaluating the effects of interventions to improve consumers' medicines use. Systematically assembling the evidence across reviews allows identification of effective or promising interventions to improve consumers’ medicines use, as well as those for which the evidence indicates ineffectiveness or uncertainty. Decision makers faced with implementing interventions to improve consumers' medicines use can use this overview to inform decisions about which interventions may be most promising to improve particular outcomes. The intervention taxonomy may also assist people to consider the strategies available in relation to specific purposes, for example, gaining skills or being involved in decision making. Researchers and funders can use this overview to identify where more research is needed and assess its priority. The limitations of the available literature due to the lack of evidence for important outcomes and important populations, such as people with multimorbidity, should also be considered in practice and policy decisions.

This overview summarised the evidence from 75 systematic reviews on consumers' medicine use published to March 2012. Reviews covered acute and chronic diseases in diverse populations and settings; and evaluated a wide range of strategies to improve medicines use, including support for behaviour change, risk minimisation and skills acquisition. Medicines adherence was the most commonly-reported outcome, with others such as knowledge and clinical outcomes also reported. Adverse events were identified less often. Collectively, the results suggest that there are many different potential pathways through which consumers' use of medicines could be targeted to improve outcomes. However, no single strategy improved all medicines-use outcomes across all diseases, populations or settings. Strategies that appear to improve medicines use include medicines self-monitoring and self-management programmes, while simplified dosing regimens and directly involving pharmacists in medicines management (eg medicines reviews) appear promising. Other strategies, such as delayed antibiotic prescriptions; practical management tools (eg reminders, packaging); education or information combined with other strategies (eg self-management skills training, counselling); and financial incentives, may also have some positive effects, but their effects are less consistent. Some strategies, such as directly observed therapy, may be ineffective. Other strategies such as providing information or education alone may have variable effects, being ineffective to change some outcomes (eg medicines adherence) but improving others such as knowledge, which is key for informed medicines choices. Despite a doubling of the number of included reviews in this update, uncertainty remains about the effects of many interventions, and the evidence on what works was particularly sparse for several populations, including children and young people, carers, and people with multimorbidity. Included reviews often had methodological limitations - at study level, review level, or both - meaning results should be interpreted with caution.

10.1002/14651858.CD007768.pub3

cochrane-simplification-train-3307

cochrane-simplification-train-3307

Twenty-eight randomised controlled trials comprising 3940 participants were included. The most frequent reasons for exclusion were non-randomised trials and the inclusion of women with metastatic disease. A wide range of interventions were evaluated, with 24 trials investigating a cognitive behavioural therapy and four trials investigating psychotherapy compared to control. Pooled standardised mean differences (SMD) from baseline indicated less depression (SMD -1.01, 95% confidence interval (CI) -1.83 to -0.18; P = 0.02; 7 studies, 637 participants, I2 = 95%, low quality evidence), anxiety (SMD -0.48, 95% CI -0.76 to -0.21; P = 0.0006; 8 studies, 776 participants, I2 = 64%, low quality evidence) and mood disturbance (SMD -0.28, 95% CI -0.43 to -0.13; P = 0.0003; 8 studies, 1536 participants, I2 = 47%, moderate quality evidence) for the cognitive behavioural therapy group than the control group. For quality of life, only an individually-delivered cognitive behavioural intervention showed significantly better quality of life than the control with an SMD of 0.65 (95% CI 0.07 to 1.23; P = 0.03; 3 studies, 141 participants, I2 = 41%, very low quality evidence). Pooled data from two group-delivered studies showed a non-significant overall survival benefit favouring cognitive behavioural therapy compared to control (pooled hazard ratio (HR) 0.76, 95% CI 0.25 to 2.32; P = 0.63; 530 participants, I2 = 84%, low quality evidence). Four studies compared psychotherapy to control with one to two studies reporting on each outcome. The four studies were assessed as high risk of bias and provided limited evidence of the efficacy of psychotherapy. Adverse events were not reported in any of the included studies. A psychological intervention, namely cognitive behavioural therapy, produced favourable effects on some psychological outcomes, in particular anxiety, depression and mood disturbance. However, the evidence for survival improvement is still lacking. These findings are open to criticism because of the notable heterogeneity across the included studies and the shortcomings of the included studies.

The evidence was current to May 2013. An intervention could be delivered in a group setting (group intervention), as one to one contact between a therapist and a patient (individual intervention) or in the form of couple therapy where the patient and her spouse attends the therapy sessions (couple intervention). The control group could receive educational leaflets or have access to seminars or relaxation classes. A comprehensive search of the literature was conducted and 28 studies comprising 3940 participants were included. The majority (24 out of 28 studies) of interventions were based on cognitive behavioural therapy, which involves changing a person's thoughts and behaviour. Four studies used psychotherapy as the intervention. Generally, the methods for assessing outcomes (such as anxiety, depression, quality of life) after the intervention and the timing of these assessments were not uniform across studies. Women who received cognitive behavioural therapy showed important reductions in anxiety, depression and mood disturbance, especially when it was delivered to groups of women. An improvement in quality of life was observed when women received individual cognitive behavioural therapy compared to the control group. The effects on survival were uncertain because the results were imprecise. The four psychotherapy studies reported limited information for each outcome. Therefore no firm conclusion could be made about the efficacy of psychotherapy. Adverse events were not reported in any of the included studies. Further research should aim to provide evidence for people to make informed decisions about whether the effects of these treatments are sustainable after discontinuation of the therapy. The quality of evidence ranged from very low quality (for example for quality of life, individually delivered intervention) to moderate quality evidence (for mood disturbance). The interventions varied between studies as did the methods and timing of outcome measures and treatment received within the control groups.

10.1002/14651858.CD008729.pub2

cochrane-simplification-train-3308

cochrane-simplification-train-3308

We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma. Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease. Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin, bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants). Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group. Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants). An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events. The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel.

We found six randomised controlled trials and three observational studies that assessed the effects of HAART plus chemotherapy compared with HAART alone; HAART plus chemotherapy compared with HAART plus another chemotherapy regimen; and chemotherapy compared with chemotherapy in the time before HAART was available. Of the nine included studies, seven included patients with a mix of mild to moderate (T0) Kaposi's sarcoma and severe (T1) Kaposi's sarcoma. There was no universal definition for what severity of disease was considered chemotherapy-requiring. For this review, we only extracted data for 792 HIV infected adults with severe Kaposi's sarcoma disease. The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, in choosing among different chemotherapy regimens, there was no observed difference between liposomal doxorubcin, liposomal daunorubicin, and paclitaxel. The overall quality of evidence in this review can be described as moderate.

10.1002/14651858.CD003256.pub2

cochrane-simplification-train-3309

cochrane-simplification-train-3309

There are no included trials. We found no randomised controlled trials that assessed the effect of antenatal fetal surveillance regimens of a suspected LGA fetus on important health outcomes for the mother and baby. There has been a rise in the prevalence of LGA babies over the past few decades in many countries. Research is therefore required on regimens of antenatal surveillance of suspected LGA infants, in order to guide practice and improve the health outcomes for the mother and infant. In particular, randomised control trials to investigate whether serial antenatal clinic and ultrasound assessments of suspected LGA infants (including liquor volume and markers of fetal adiposity) would be useful, to assess whether surveillance methods improve health outcomes. In addition, as there are concerns that identifying suspected LGA fetuses may lead to unnecessary maternal anxiety, investigations and interventions, any such trial would need to assess the risks as well as benefits of regimens of fetal surveillance for suspected LGA fetuses.

We searched for studies on 10 August 2015 but did not find any randomised controlled trials looking at the effects of performing extra tests on health outcomes in pregnant women with overgrowth of the baby after 20 weeks gestation. There is a need for randomised controlled trials in this area in order to inform clinical practice when large babies are identified during a pregnancy, to assess if extra tests or surveillance can improve the health of these women and their babies. It is also important to identify any harms associated with extra tests and surveillance, as identifying women with suspected large babies may lead to unnecessary maternal anxiety with additional investigations and interventions, including induction of labour or caesarean section.

10.1002/14651858.CD011739.pub2

cochrane-simplification-train-3310

cochrane-simplification-train-3310

Only one randomised trial met our inclusion criteria, despite our initial search yielding 141 citations. This was a small study, with 17 people completing a trial comparing CBT to an attention placebo (supportive psychotherapy) for people with delusional disorder. Most participants were already taking medication and this was continued during the trial. We were not able to include any randomised trials on medications of any type due to poor data reporting, which left us with no usable data for these trials. For the included study, usable data were limited, risk of bias varied and the numbers involved were small, making interpretation of data difficult. In particular there were no data on outcomes such as global state and behaviour, nor any information on possible adverse effects. A positive effect for CBT was found for social self esteem using the Social Self-Esteem Inventory (1 RCT, n = 17, MD 30.5, CI 7.51 to 53.49, very low quality evidence), however this is only a measure of self worth in social situations and may thus not be well correlated to social function. More people left the study early if they were in the supportive psychotherapy group with 6/12 leaving early compared to 1/6 from the CBT group, but the difference was not significant (1 RCT, n = 17, RR 0.17, CI 0.02 to 1.18, moderate quality evidence). For mental state outcomes the results were skewed making interpretation difficult, especially given the small sample. Despite international recognition of this disorder in psychiatric classification systems such as ICD-10 and DSM-5, there is a paucity of high quality randomised trials on delusional disorder. There is currently insufficient evidence to make evidence-based recommendations for treatments of any type for people with delusional disorder. The limited evidence that we found is not generalisable to the population of people with delusional disorder. Until further evidence is found, it seems reasonable to offer treatments which have efficacy in other psychotic disorders. Further research is needed in this area and could be enhanced in two ways: firstly, by conducting randomised trials specifically for people with delusional disorder and, secondly, by high quality reporting of results for people with delusional disorder who are often recruited into larger studies for people with a variety of psychoses.

This review aimed to assess the effectiveness of all current treatments for people with delusional disorder. A search for randomised controlled trials was run in 2012. Authors found 141 citations in the search but only one trial, randomising 17 people, could be included in the review. The study compared the effectiveness of CBT with supportive psychotherapy for people with delusional disorder. Participants were already taking medication and this was continued during the trial. The review was not able to include any studies or trials involving medications of any type used to treat delusional disorder. For the study that was included, there was limited information presented that we could use. Firm conclusions were difficult to make and no evidence on improving people's behaviour and overall mental health was available. More people left the study early from the supportive psychotherapy group, but number of participants was small and the overall difference between the groups was not enough to conclude one treatment was better than the other. A positive effect for CBT was found for people's social self esteem, although again, this finding is limited by the low quantity and quality of the data and does not relate to people's social or everyday functioning. Currently there is an overall lack of high quality evidence-based information about the treatment of delusional disorders and insufficient evidence to make recommendations for treatments of any type. Until such evidence is found, the treatment of delusional disorders will most likely include those that are considered effective for other psychotic disorders and mental health problems. Further large-scale and high quality research is needed in this area. Research could be improved by conducting trials specifically for people with delusional disorder. Ben Gray, Senior Peer Researcher, McPin Foundation: http://mcpin.org/.

10.1002/14651858.CD009785.pub2

cochrane-simplification-train-3311

cochrane-simplification-train-3311

We included four randomised controlled trials (RCTs). We found evidence of missing data and poor reporting. When bifeprunox 20 mg was compared with placebo for schizophrenia, the drug resulted in a reduction of the Positive and Negative Syndrome Scale (PANSS) positive subscale score regarding positive symptoms (n = 549, 2 RCTs, MD -1.89, 95% CI -2.85 to -0.92, low-quality evidence) and the PANSS negative subscale regarding negative symptoms (n = 549, 2 RCTs, MD -1.53, 95% CI -2.37 to -0.69, low-quality evidence). There was a clear improvement regarding deterioration in the bifeprunox 20 mg group (n = 231, 1 RCT, RR 0.71 95% CI, 0.54 to 0.93, very low-quality evidence). The total number of participants with equal to or greater than 7% weight increase was similar between bifeprunox and placebo (n = 483, 1 RCT, RR 1.02 95% CI 0.31 to 3.33 moderate-quality evidence). There were no useable data for quality of life, economic outcomes, and service use. Our results showed some positive effects and a favourable adverse effect profile for bifeprunox, although there were few data overall and none were of high quality. It would seem that these data alone would not have been enough for the FDA to decide to halt progress of the drug to market. We can only assume that we are missing important data. Both the FDA and the relevant pharmaceutical companies have not made all relevant data accessible. As some of these trials also involved an additional haloperidol, olanzapine, quetiapine, or risperidone arm, these data are not only relevant to evaluation of bifeprunox. In not making all data accessible, it is hard to see how the FDA and the drug companies have fulfilled their full obligations to people with schizophrenia or their clinicians.

The Information Specialist of the Cochrane Schizophrenia Group searched the specialised register in October 2015. He ran an electronic search for trials that randomised people with schizophrenia to receive either bifeprunox or placebo, finding 42 records. The review authors screened these for inclusion in the review. Only four trials provided useable data, and these were of poor quality with some evidence of missing data. Two trials are completed but not yet published; we could not obtain any information from these trials that we could use in this review. The data available to us showed that bifeprunox improved participants' scores on both positive and negative symptom scales. Weight increase was similar between those receiving bifeprunox and those allocated to placebo. Data regarding the effects of bifeprunox are scarce. The data we found, which were of poor quality, showed no real evidence that bifeprunox is unsafe or ineffective. Its effects do not seem significantly different to other drugs that are currently on the market. More data on this compound exists but is not publicly available. We believe that the licencing authority in the USA must have had more information on which to base their important decision. The drug company also seemed to lose the will to move forward with bifeprunox. Whether or not the decision to prohibit access to a potentially useful drug was taken because of clear evidence of adverse effects, market calculations, or biases, it would seem an omission that all information upon which this decision was made is not in the public domain.

10.1002/14651858.CD012029.pub2

cochrane-simplification-train-3312

cochrane-simplification-train-3312

Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

We could only include one small study in the review (14 participants) and this was stopped early because not enough people agreed to join the study as volunteers. The study lasted six months and compared omalizumab (Xolair®) injections under the skin of the upper arm or the thigh to placebo injections (dummy treatment containing no active medication). Volunteers were given of 600 mg of omalizumab or placebo daily along with itraconazole (an antifungal drug) twice daily and oral corticosteroids, with a maximum daily dose of 400 mg. The full results of the study were not published. Only limited results on side effects were published online. Six out of nine volunteers (66.67%) in the omalizumab group and one out of five volunteers (20%) in the placebo group reported one or more serious side effects. Due to the lack of evidence, we are not able to make recommendations either in favour of, or against the use of, anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. More research into this treatment is needed.

10.1002/14651858.CD010288.pub4

cochrane-simplification-train-3313

cochrane-simplification-train-3313

We found 8 RCTs with 11,164 participants but one study did not provide enough data. Studies compared VCT to no VCT and education to no intervention and to alternative education. VCT uptake increased to 51% when provided at the workplace compared to a voucher for VCT (RR=14.0 (95% CI 11.8 to16.7)). After VCT, self-reported STD decreased (RR = 0.10 (95% CI 0.01 to 0.73)) but HIV incidence (RR=1.4 (95% CI 0.7 to 2.7)) and unprotected sex (RR=0.71 (0.48 to 1.06)) did not decrease significantly. . Education reduced STDs (RR = 0.68 (95%CI 0.48 to 0.96)), unprotected sex (Standardised Mean Difference (SMD)= -0.17 (95% CI -0.29 to -0.05), sex with a commercial sex worker (RR = 0.88 (95% CI 0.81 to 0.96) but not multiple sexual partners (Mean Difference (MD) = -0.22 (95% CI -0.52 to 0.08) nor use of alcohol before sex (MD = -0.01 (95% CI of -0.11 to 0.08). Workplace interventions to prevent HIV are feasible. There is moderate quality evidence that VCT offered at the work site increases the uptake of testing. Even though this did no lower HIV-incidence, there was a decrease in self-reported sexual transmitted diseases and a decrease in risky sexual behaviour. There is low quality evidence that educational interventions decrease sexually transmitted diseases, unprotected sex and sex with commercial sex workers but not sex with multiple partners and the use of alcohol before sex. More and better randomised trials are needed directed at high risk groups such as truck drivers or workers in areas with a very high HIV prevalence such as Southern Africa. Risky sexual behaviour should be measured in a standardised way.

We included eight studies with 11,164 participants but one study did not provide enough data to be useful. One study from Africa found a strong increase in uptake of Voluntary Counseling and Testing (VCT) to 51% when delivered on-site which was 14 times more compared to a voucher for off-site testing. However, VCT did not change HIV incidence in one study among African factory workers. In another study among HongKong truck drivers, VCTdecreased self-reported sexually transmitted diseases (STD) but VCT did not decrease unprotected sex significantly. Education was studied among soldiers in Nigeria, Angola and the US, truck drivers in India and factory workers in Thailand.. Education that was modelled after a motivational theory reduced STDs with 32%, decreased unprotected sex with a small amount, reduced sex with a commercial sex worker with 12% but did not decrease the number of partners or the habit of using alcohol before sex. We concluded that workplace interventions for preventing HIV are feasible and that it is possible to study them in a randomised controlled trial. Peer influence has a positive effect on VCT uptake and workplace interventions can change risky sexual behaviour to a moderate degree. More randomised trials are needed in high risk groups or in areas with high HIV prevalence to find more effective interventions.

10.1002/14651858.CD005274.pub3

cochrane-simplification-train-3314

cochrane-simplification-train-3314

We included seven studies with a total of 138 participants, with data available for 123. Sample sizes ranged from 9 to 37. Judgements for categories of risk of bias varied: concerns were greatest regarding allocation concealment, blinding of outcome assessors, and incomplete outcome data (dropout rates in the five community-based studies ranged from 3% to 54% and results were usually analysed on a per protocol basis). Participant characteristics in the seven studies were heterogeneous, but the vast majority had convictions for sexual offences, ranging from exhibitionism to rape and child molestation. Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA); a seventh evaluated two antipsychotics (benperidol and chlorpromazine). Five studies were placebo-controlled; in two, MPA was administered as an adjunctive treatment to a psychological therapy (assertiveness training or imaginal desensitisation). Meta-analysis was not possible due to heterogeneity of interventions, comparators, study designs, and other issues. The quality of the evidence overall was poor. In addition to methodological issues, much evidence was indirect. Primary outcome: recividism. Two studies reported recidivism rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reports of recividism at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of recidivism amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm of this study (n = 5) dropped out immediately, despite treatment being court mandated. Two studies did not report recidivism rates as they both took place in one secure psychiatric facility from which no participant was discharged during the study, whilst another three studies did not appear directly to measure recividism but rather abnormal sexual activity alone. Secondary outcomes:The included studies report a variety of secondary outcomes. Results suggest that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself (three studies). Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and with anxiety (two studies). One study measured anxiety formally; one study measured anger or aggression. Adverse events: Six studies provided information on adverse events. No study tested the effects of testosterone-suppressing drugs beyond six to eight months and the cross-over design of some studies may obscure matters (given the 'rebound effect' of some hormonal treatments). Considerable weight gain was reported in two trials of oral MPA and CPA. Side effects of intramuscular MPA led to discontinuation in some participants after three to five injections (the nature of these side effects was not described). Notable increases in depression and excess salivation were reported in one trial of oral MPA. The most severe side effects (extra-pyramidal movement disorders and drowsiness) were reported in a trial of antipsychotic medication for the 12 participants in the study. No deaths or suicide attempts were reported in any study. The latter is important given the association between antilibidinal hormonal medication and mood changes. We found only seven small trials (all published more than 20 years ago) that examined the effects of a limited number of drugs. Investigators reported issues around acceptance and adherence to treatment. We found no studies of the newer drugs currently in use, particularly SSRIs or GnRH analogues. Although there were some encouraging findings in this review, their limitations do not allow firm conclusions to be drawn regarding pharmacological intervention as an effective intervention for reducing sexual offending. The tolerability, even of the testosterone-suppressing drugs, was uncertain given that all studies were small (and therefore underpowered to assess adverse effects) and of limited duration, which is not consistent with current routine clinical practice. Further research is required before it is demonstrated that their administration reduces sexual recidivism and that tolerability is maintained. It is a concern that, despite treatment being mandated in many jurisdictions, evidence for the effectiveness of pharmacological interventions is so sparse and that no RCTs appear to have been published in two decades. New studies are therefore needed and should include trials with larger sample sizes, of longer duration, evaluating newer medications, and with results stratified according to category of sexual offenders. It is important that data are collected on the characteristics of those who refuse and those who drop out, as well as those who complete treatment.

We found seven randomised trials involving 138 participants, which provided data on 123. All were male, aged between 16 and 68 years. Offending ranged from very serious (e.g., rape) to minor criminality (e.g., exhibitionism). Comparators included placebo (five studies), psychological treatment (one study), and a combination of psychological and pharmacological treatment (one study). Five studies took place in the community and two in a secure hospital. Duration varied between three and 13 months. Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA). In two of these studies, MPA was given alongside a psychological therapy (assertiveness training or imaginal desensitisation). The seventh study assessed the effectiveness of two antipsychotics (benperidol and chlorpromazine) versus placebo. Meta-analysis was not possible due to heterogeneity of interventions, comparator groups, study designs, and other issues. Two studies reported reoffending rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reoffending at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of reoffending amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm (n = 5) dropped out immediately, despite treatment being court mandated. Two studies did not report reoffending rates as they both took place in a secure psychiatric facility from which none were discharged. Three community studies did not formally report reoffending at all, focusing largely on 'abnormal sexual activity'. Secondary outcomes: Studies reported a variety of secondary outcomes. Results suggested that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself. Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and anxiety. One study measured anxiety formally; one study measured anger/aggression. Adverse events: Six studies provided information on adverse events and none tested the effects of testosterone-suppressing drugs beyond six to eight months. The most severe were reported in a trial of antipsychotic medication. Reported side effects in two trials of oral MPA and CPA included considerable weight gain. Side effects of intramuscular MPA led to discontinuation in some participants. Important increases in depression and excess salivation were reported in one trial of oral MPA. No deaths and no suicide attempts were reported in any study. We conclude that these seven trials (published more than 20 years ago), examining only a limited number of drugs, provide a poor evidence base to guide practice. Not only were the trials small, they were of short duration, included varied participants, and none trialled the newer drugs currently in use, particularly SSRIs or GnRH analogues. The results of this review, therefore, do not allow firm conclusions to be drawn regarding pharmacological interventions as an effective intervention for reducing sexual offending. New studies are needed that address these deficits. Data should also be collected on the characteristics of those who refuse, drop out, and complete treatment. Overall, the quality of the evidence was poor. We had concerns about: number of participants leaving studies, blinding of those who measured outcomes, ways in which investigators concealed allocation of treatment to those delivering it, and reporting of our primary outcome: reoffending.

10.1002/14651858.CD007989.pub2

cochrane-simplification-train-3315

cochrane-simplification-train-3315

We screened 2686 citations and included two trials enrolling 95 participants and one cohort study enrolling 17 participants. We assessed one randomized controlled trial as being at unclear risk of bias, and the other at high risk of bias; we assessed the non-randomized study as being at high risk of bias. We were unable to pool data due to the small number of studies meeting our inclusion criteria and therefore present narrative results rather than meta-analyses. One trial of 75 participants reported that extubation success (defined as no need for reintubation within 48 hours) was higher in the mechanical insufflation-exsufflation (MI-E) group (82.9% versus 52.5%, P < 0.05) (risk ratio (RR) 1.58, 95% confidence interval (CI) 1.13 to 2.20, very low-quality evidence). No study reported weaning success or reintubation as distinct from extubation success. One trial reported a statistically significant reduction in mechanical ventilation duration favouring MI-E (mean difference -6.1 days, 95% CI -8.4 to -3.8, very low-quality evidence). One trial reported mortality, with no participant dying in either study group. Adverse events (reported by two trials) included one participant receiving the MI-E protocol experiencing haemodynamic compromise. Nine (22.5%) of the control group compared to two (6%) MI-E participants experienced secretion encumbrance with severe hypoxaemia requiring reintubation (RR 0.25, 95% CI 0.06 to 1.10). In the lung volume recruitment trial, one participant experienced an elevated blood pressure for more than 30 minutes. No participant experienced new-onset arrhythmias, heart rate increased by more than 25%, or a pneumothorax. For outcomes assessed using GRADE, we based our downgrading decisions on unclear risk of bias, inability to assess consistency or publication bias, and uncertainty about the estimate of effect due to the limited number of studies contributing outcome data. The overall quality of evidence on the efficacy of cough augmentation techniques for critically-ill people is very low. Cough augmentation techniques when used in mechanically-ventilated critically-ill people appear to result in few adverse events.

We found two randomized controlled trials (95 adult participants) and one non-randomized controlled study (17 children aged at least four weeks) conducted in Portugal, Canada, and the United States. We rated the two randomized trials as being of unclear quality and the non-randomized study as being low quality. The largest randomized trial (75 participants) found a 83% success rate for extubation with mechanically- and manually-assisted cough used in combination, compared with 53% in the control group (extubation success over 1½ times more likely) (very low-quality evidence). The time spent on a ventilator was six days less in people using mechanically- and manually-assisted cough (very low-quality evidence). No participants died in this trial. Complications were reported by the two randomized trials. One person receiving mechanically-assisted cough experienced a prolonged drop in blood pressure; another person receiving breathstacking and suctioning in addition to manually-assisted cough experienced a prolonged rise in blood pressure. In one trial, following removal of the breathing tube, more people in the group not receiving mechanically-assisted cough experienced secretion retention, a drop in oxygen levels, and needed the breathing tube to be reinserted (nine people compared with two, very low-quality evidence). The non-randomized study reported that the breathing tube could be removed in all of the six children in the group receiving interventions to assist with coughing. In this non-randomized study, death was only reported for children receiving a cough-promoting technique. One child died, but this was not thought to be related to the cough technique. This study did not report adverse events associated with assisted coughing. No included study evaluated a single cough-promoting technique in isolation. The two randomized trials combined manually-assisted cough with either mechanical assistance (MI-E) or breathstacking, and the non-randomized study used all three methods. Very low-quality evidence from single trial findings suggests that cough-promoting techniques might increase successful removal of the breathing tube and decrease the time spent on mechanical ventilation, while not causing harm. The limited participant numbers made it difficult to determine the likelihood of harms.

10.1002/14651858.CD011833.pub2

cochrane-simplification-train-3316

cochrane-simplification-train-3316

Our search strategy identified 60 studies for consideration, of which 27 randomised trials involving 17,808 women undergoing caesarean section were included in the review. Overall, the methodological quality of the trials was variable, with 12 of the 27 included trials adequately describing the randomisation sequence, with less than half describing adequately methods of allocation concealment, and only six trials indicating blinding of outcome assessors. Two trials compared auto-suture devices with traditional hysterotomy involving 300 women. No statistically significant difference in febrile morbidity between the stapler and conventional incision groups was apparent (risk ratio (RR) 0.92; 95% confidence interval (CI) 0.38 to 2.20). Five studies were included in the review that compared blunt versus sharp dissection when performing the uterine incision involving 2141 women. There were no statistically significant differences identified for the primary outcome febrile morbidity following blunt or sharp extension of the uterine incision (four studies; 1941 women; RR 0.86; 95% CI 0.70 to 1.05). Mean blood loss (two studies; 1145 women; average mean difference (MD) -55.00 mL; 95% CI -79.48 to -30.52), and the need for blood transfusion (two studies; 1345 women; RR 0.24; 95% CI 0.09 to 0.62) were significantly lower following blunt extension. A single trial compared transverse with cephalad-caudad blunt extension of the uterine incision, involving 811 women, and while mean blood loss was reported to be lower following transverse extension (one study; 811 women; MD 42.00 mL; 95% CI 1.31 to 82.69), the clinical significance of such a small volume difference is of uncertain clinical relevance. There were no other statistically significant differences identified for the limited outcomes reported. A single trial comparing chromic catgut with polygactin-910, involving 9544 women reported that catgut closure versus closure with polygactin was associated with a significant reduction in the need for blood transfusion (one study, 9544 women, RR 0.49, 95% CI 0.32 to 0.76) and a significant reduction in complications requiring re-laparotomy (one study, 9544 women, RR 0.58, 95% CI 0.37 to 0.89). Nineteen studies were identified comparing single layer with double layer closure of the uterus, with data contributed to the meta-analyses from 14 studies. There were no statistically significant differences identified for the primary outcome, febrile morbidity (nine studies; 13,890 women; RR 0.98; 95% CI 0.85 to 1.12). Although the meta-analysis suggested single layer closure was associated with a reduction in mean blood loss, heterogeneity is high and this limits the clinical applicability of the result. There were no differences identified in risk of blood transfusion (four studies; 13,571 women; average RR 0.86; 95% CI 0.63 to 1.17; Heterogeneity: Tau² = 0.15; I² = 49%), or other reported clinical outcomes. Caesarean section is a common procedure performed on women worldwide. There is increasing evidence that for many techniques, short-term maternal outcomes are equivalent. Until long-term health effects are known, surgeons should continue to use the techniques they prefer and currently use.

The review authors searched the medical literature for randomised controlled trials to inform the most appropriate surgical techniques to use. Twenty-seven trials involving 17,808 women from a number of different countries contributed to the review. None of these trials assessed the type of uterine incision (side to side (transverse) lower uterine segment incision versus other types of uterine incision). Results from 18 randomised trials contributed to reports that single layer closure of the uterine incision was associated with a reduction in blood loss, and duration of the procedure. In these studies the surgical procedure for entering the abdominal cavity also differed and could have contributed to blood loss and duration of surgery. Five trials compared blunt with sharp dissection at the time of the uterine incision (2141 women) and a further two trials auto-suture devices with standard hysterotomy (300 women). Blunt surgery was associated with a reduction in mean blood loss at the time of the procedure. The use of an auto-suture instrument did not clearly reduce procedural blood loss but increased the duration of the procedure. Overall, trials focused on blood loss and duration of the operative procedure rather than clinical outcomes for the women. The methodological quality of the trials was variable.

10.1002/14651858.CD004732.pub3

cochrane-simplification-train-3317

cochrane-simplification-train-3317

Two trial were identified. The European Atrial Fibrillation Trial (EAFT) involving 455 patients, who received either anticoagulants (International Normalised Ratio (INR) 2.5 to 4.0), or aspirin (300 mg/day). Patients joined the trial within three months of transient ischemic attack or minor stroke. The mean follow up was 2.3 years. In the Studio Italiano Fibrillazione Atriale (SIFA) trial, 916 patients with NRAF and a TIA or minor stroke within the previous 15 days were randomised to open label anticoagulants (INR 2.0 to 3.5) or indobufen (a reversible platelet cyclooxygenase inhibitor, 100 or 200 mg BID). The follow-up period was one year. The combined results show that anticoagulants were significantly more effective than antiplatelet therapy both for all vascular events (Peto odds ratio (Peto OR) 0.67, 95% confidence interval (CI) 0.50 to 0.91) and for recurrent stroke (Peto OR 0.49, 95% CI 0.33 to 0.72). Major extracranial bleeding complications occurred more often in patients on anticoagulants (Peto OR 5.16, 95% CI 2.08 to 12.83), but the absolute difference was small (2.8% per year versus 0.9% per year in EAFT and 0.9% per year versus 0% in SIFA). Warfarin did not cause a significant increase of intracranial bleeds. The evidence from two trials suggests that anticoagulant therapy is superior to antiplatelet therapy for the prevention of stroke in people with NRAF and recent non-disabling stroke or TIA. The risk of extracranial bleeding was higher with anticoagulant therapy than with antiplatelet therapy.

Anticoagulants are more effective than antiplatelet drugs to prevent a second stroke in people with atrial fibrillation. Nonrheumatic atrial fibrillation (NRAF) is a heart rhythm disorder commonly found in patients who have had a stroke. Patients with NRAF have an irregular heart beat. This can cause the formation of a blood clot in the left atrium of the heart. This clot may break away and block a cerebral artery, thus causing a stroke. Patients who have had a stroke in the presence of NRAF have a high risk of another stroke. Anticoagulant drugs, such as warfarin, make the blood 'thinner' and prevent the formation of blood clots and hence could prevent stroke. However, anticoagulant drugs may also cause bleeding in the brain and this complication could offset any benefits. Aspirin may be a safer alternative. This review identified two trials in which patients with NRAF who had a stroke were treated with anticoagulants or antiplatelet therapy. These studies show that anticoagulants are superior to antiplatelet agents to reduce the risk of recurrent stroke.

10.1002/14651858.CD000187.pub2

cochrane-simplification-train-3318

cochrane-simplification-train-3318

Of 2091 titles and abstracts identified, full text versions of only three  (Morgan 2007; Murdoch 1999; Netsell 2001) were obtained. 2088 were excluded, largely on the basis of not including dysarthria, being diagnostic or descriptive papers, and for concerning adults rather than children. Morgan 2007 and Murdoch 1999 were excluded for not employing RCT or quasi-randomised methodology; Netsell 2001 on the basis of being a theoretical review paper, rather than an intervention study. Five references were identified and obtained from the bibliography of the Murdoch 1999 paper. All were excluded due to including populations without ABI, adults with dysarthria, or inappropriate design. Thus, no studies met inclusion criteria. The review demonstrates a critical lack of studies, let alone RCTs, addressing treatment efficacy for dysarthria in children with ABI. Possible reasons to explain this lack of data include i) a lack of understanding of the characteristics or natural history of dysarthria associated with this population; ii) the lack of a diagnostic classification system for children precluding the development of well targeted intervention programs; and iii) the heterogeneity of both the aetiologies and resultant possible dysarthria types of paediatric ABI. Efforts should first be directed at modest well-controlled studies to identify likely efficacious treatments that may then be trialed in multi-centre collaborations using quasi-randomised or RCT methodology.

Although this research reports that  positive gains have been reported from a case-based study of a child with dysarthria following ABI (specifically with traumatic brain injury), there are currently too few studies performed in this area to draw any conclusions about the efficacy of treatment for dysarthria in children and teenagers. This review therefore calls for Speech Language Pathologists/Speech Language Therapists (SLPs/SLTs) working in this area to perform studies of the natural history and treatment efficacy of this group.

10.1002/14651858.CD006279.pub2

cochrane-simplification-train-3319

cochrane-simplification-train-3319

Three studies met the inclusion criteria for this review. Two studies used clomipramine and one used tianeptine. All three trials were small, with between 12 and 32 participants. One of the clomipramine trials involved children and young adults, while the other two trials enrolled only children. Due to heterogeneity in study participant characteristics, the TCA medications investigated and the outcome measures used, we were not able to perform any meta-analysis. In only one of the three studies was there any indication that giving children tianeptine could be effective in the short term. In this study, parents and teachers reported that it reduced irritability, hyperactivity, inadequate eye contact and inappropriate speech, but clinician ratings found no significant impact on these symptoms. There were also significant adverse effects, including increased drowsiness and reduced activity levels in these individuals while being treated with tianeptine. The evidence of the impact of clomipramine in the two studies is contradictory. There was evidence of improvement in autistic symptoms, irritability and obsessive-compulsive disorder type symptoms, but conflicting evidence in relation to hyperactivity across the two studies, and no significant changes found with inappropriate speech. There were also adverse effects reported with the use of clomipramine. Although side effect ratings were not significantly different to placebo, there were significant dropout rates in the clomipramine arm of one study. Clinicians considering the use of TCAs need to be aware of the limited and conflicting evidence of effect and the side effect profile when discussing this treatment option with people who have ASD and their carers. Further research is required before TCAs can be recommended for treatment of individuals with ASD.

We found three trials that studied two different TCAs - clomipramine and tianeptine. One of the clomipramine studies involved children and young adults; the other two studies enrolled only children. All three trials were small, with between 12 and 32 participants. There is only limited evidence to support the use of clomipramine or tianeptine in the treatment of individuals with ASD, and some evidence of side effects that would limit their usefulness. Clinicians considering the use of TCAs in ASD need to be aware of the limited and conflicting evidence of effect and the side effect profile of TCAs when discussing this treatment option with patients with ASD and their carers. More research is required before TCAs can be recommended for use in ASD.

10.1002/14651858.CD008372.pub2

cochrane-simplification-train-3320

cochrane-simplification-train-3320

Six trials involving 705 patients were included. Mortality was not significantly different between groups, which was low in both the primary repair (1.94%) and the diverted groups (1.74%). The Peto OR for mortality was 1.22 (95% CI 0.40 to 3.74). However, the primary repair group experienced a significantly lower rate of complications (Peto OR 0.54; 95% CI 0.39 to 0.76), total infectious complications (Peto OR 0.44; 95% CI 0.17 to 1.1), abdominal infections including dehiscence (Peto OR 0.67; 95% CI 0.35 to 1.3), abdominal infections excluding dehiscence (Peto OR 0.69; 95% CI 0.34 to 1.39), wound complications including dehiscence (Peto OR 0.73; 95% CI 0.38 to 1.39), and wound complications excluding dehiscence (Peto OR 0.67; 95% CI 0.32 to 1.39). Statistical significance favoring primary repair over fecal diversion was achieved for all outcomes related to abdominal infections and wound complications when one study was excluded for both clinical and statistical heterogeneity in the sensitivity analysis. Meta-analysis of currently published randomized controlled trials favors primary repair over fecal diversion for penetrating colon injuries.

The review authors searched the medical literature and found six controlled studies in which patients were randomized to primary repair or fecal diversion. Results were reported for a total of 705 patients. The two groups sustained significant injuries with the primary repair patients at least as ill as the diverted patients. The studies were reported from 1979 to 2002 and involved increasingly 'high risk' patients. Five were conducted in the United States and one in South Africa. Primary closure was at least as safe as fecal diversion. The number of deaths was similar in both the primary repair (1.94%) and the diverted groups (1.74%). Total complications, total infectious complications, abdominal infections and wound complications all favored primary repair. The studies did not adequately report colostomy closure for trauma-related colostomies, which can itself result in complications and significant illness.

10.1002/14651858.CD002247

cochrane-simplification-train-3321

cochrane-simplification-train-3321

Three studies (a total of 112 participants) were included. All studies randomised participants to a singing group or a control group. The comparison groups included a film workshop, handcraft work, and no intervention. The frequency of the singing intervention in the studies ranged from 1 to 2 times a week over a 6 to 24 week period. The duration of each singing session was 60 minutes. All studies included participants diagnosed with COPD with a mean age ranging from 67 to 72 years and a mean forced expiratory volume in one second (FEV1) ranging from 37% to 64% of predicted values. The sample size of included studies was small (33 to 43 participants) and overall study quality was low to very low. Blinding of personnel and participants was not possible due to the physical nature of the intervention, and selection and reporting bias was present in two studies. For the primary outcome of health-related quality of life, there was no statistically significant improvement in the St George's Respiratory Questionnaire total score (mean difference (MD) -0.82, 95% confidence interval (CI) -4.67 to 3.02, 2 studies, n = 58, low-quality evidence). However, there was a statistically significant improvement in the SF-36 Physical Component Summary (PCS) score favouring the singing group (MD 12.64, 95% CI 5.50 to 19.77, 2 studies, n = 52, low-quality evidence). Only one study reported results for the other primary outcome of dyspnoea, in which the mean improvement in Baseline Dyspnoea Index (BDI) score favouring the singing group was not statistically significant (MD 0.40, 95% CI -0.65 to 1.45, 1 study, n = 30, very low-quality evidence). No studies examined any long-term outcomes and no adverse events or side effects were reported. There is low to very low-quality evidence that singing is safe for people with COPD and improves physical health (as measured by the SF-36 physical component score), but not dyspnoea or respiratory-specific quality of life. The evidence is limited due to the low number of studies and the small sample size of each study. No evidence exists examining the long-term effect of singing for people with COPD. The absence of studies examining singing performed in conjunction with pulmonary rehabilitation precludes the formulation of conclusions about the effects of singing in this context. More randomised controlled trials with larger sample sizes and long-term follow-up, and trials examining the effect of singing in addition to pulmonary rehabilitation, are required to determine the effect of singing on health-related quality of life and dyspnoea in people with COPD.

We included three studies with a total of 112 participants. Participants were randomly assigned to singing training or to a non-singing control group. The control groups were either a film workshop, handcraft work, or nothing at all. The singing was performed in groups, once to twice a week for one hour, for a minimum of six weeks. There was diversity in the results of the studies and we were unable to combine many results in 'meta-analyses'. A meta-analysis is a statistical analysis which combines the results of two or more separate studies to give a pooled result. Some studies showed improvements in some aspects of quality of life, while others showed no improvement. Breathlessness was only measured in one study and no improvement was found. The studies did not report whether any effects lasted for a long time after the singing training was completed. No studies reported any side effects from singing, so singing appears to be safe for people with COPD. The studies were of low quality due to the small number of participants and missing information about the methods and some of the outcomes. We were unable to find enough evidence to sufficiently determine the effect of singing in people with COPD. More studies are required and they should concentrate on enrolling larger numbers of people.

10.1002/14651858.CD012296.pub2

cochrane-simplification-train-3322

cochrane-simplification-train-3322

Our searches identified 28 references to eight trials; five trials were excluded (three were cross-over and one was not randomised and one did not have relevant outcomes), one cross-over trial is awaiting classification pending provision of data and one trial is ongoing. The included parallel randomised controlled trial compared ataluren to placebo for a duration of 48 weeks in 238 participants (age range 6 to 53 years) with cystic fibrosis who had at least one nonsense mutation (a type of class I mutation). The quality of evidence and risk of bias assessments for the trial were moderate overall. Random sequence generation, allocation concealment and blinding of trial personnel were well-documented; participant blinding was less clear. Some participant data were excluded from the analysis. The trial was assessed as high risk of bias for selective outcome reporting, especially when reporting on the trial's post hoc subgroup of participants by chronic inhaled antibiotic use. The trial was sponsored by PTC Therapeutics Incorporated with grant support by the Cystic Fibrosis Foundation, the Food and Drug Administration's Office of Orphan Products Development and the National Institutes of Health (NIH). The trial reported no significant difference between treatment groups in quality of life, assessed by the Cystic Fibrosis Questionnaire-Revised respiratory domain score and no improvement in respiratory function measures (mean difference of relative change in forced expiratory volume at one second 2.97% (95% confidence interval -0.58 to 6.52)). Ataluren was associated with a significantly higher rate of episodes of renal impairment, risk ratio 17.70 (99% confidence interval 1.28 to 244.40). The trial reported no significant treatment effect for ataluren for the review's secondary outcomes: pulmonary exacerbation; computerised tomography score; weight; body mass index; and sweat chloride. No deaths were reported in the trial. A post hoc subgroup analysis of participants not receiving chronic inhaled tobramycin (n = 146) demonstrated favourable results for ataluren (n = 72) for relative change in % predicted forced expiratory volume at one second and pulmonary exacerbation rate. Participants receiving chronic inhaled tobramycin appeared to have a reduced rate of pulmonary exacerbation compared to those not receiving chronic inhaled tobramycin. This drug interaction was not anticipated and may affect the interpretation of the trial results. There is currently insufficient evidence to determine the effect of ataluren as a therapy for people with cystic fibrosis with class I mutations. Future trials should carefully assess for adverse events, notably renal impairment and consider the possibility of drug interactions. Cross-over trials should be avoided given the potential for the treatment to change the natural history of cystic fibrosis.

We found one trial (238 people took part) comparing ataluren to placebo (a dummy treatment with no active medication). The trial lasted 48 weeks and included both males and females aged six years and older. Everyone taking part had at least one copy of a nonsense mutation (a type of class I mutation that causes cystic fibrosis). In those people who took ataluren, there was no improvement in clinical outcomes such as quality of life, lung function, exacerbations (flare up of disease), sweat chloride (salt) levels or weight. The trial found that kidney damage was more common in people who took ataluren. The trial investigators then analysed the results in a way that they hadn't planned originally and looked at how ataluren or placebo affected people depending on whether they were using inhaled tobramycin on a long-term basis or not. They found that amongst those not taking inhaled tobramycin, lung function declined at a slower rate and there were fewer exacerbations in the ataluren group compared to the placebo group. We have not found enough high-quality evidence currently to determine the effect of ataluren for treating people with cystic fibrosis. We recommend that future trials are designed and reported clearly so that their results can be included in a systematic review. We judged the quality of the evidence was moderate with uncertainty due to how widely the results varied between participants. We are satisfied that everyone taking part had an equal chance of being in either group (ataluren or placebo) and that no one could work out which group the next person would be put into, so that healthier people did not receive the treatment and make the results seem better. We believe that the clinicians running the trial and those taking part in the trial did not know which treatment each person was receiving. We have some concerns on the emphasis the investigators have placed on the results of a comparison they had not planned (use of long-term inhaled tobramycin). Unfortunately, the trial did not report all their results clearly; sometimes they did not report them in a way that we could use in the review and sometimes they did not report the data at all. This affected the certainty with which we judged the overall results. The trial was sponsored by PTC Therapeutics Incorporated. The Cystic Fibrosis Foundation, the Food and Drug Administration's Office of Orphan Products Development and the National Institutes of Health (NIH) also supported the trial.

10.1002/14651858.CD012040.pub2

cochrane-simplification-train-3323

cochrane-simplification-train-3323

Ten studies met our inclusion criteria, all of which were conducted in Africa. Of these four were randomised controlled trials while the remaining six were cohort studies. From the trial data, when nurses initiated and provided follow-up HIV therapy, there was high quality evidence of no difference in death at one year, unadjusted risk ratio was 0.96 (95% CI 0.82 to 1.12), one trial, cluster adjusted n = 2770. There was moderate quality evidence of lower rates of losses to follow-up at one year, relative risk of 0.73 (95% CI 0.55 to 0.97). From the cohort data, there was low quality evidence that there may be an increased risk of death in the task shifting group, relative risk 1.23 (95% CI 1.14 to 1.33, two cohorts, n = 39 160) and very low quality data reporting no difference in patients lost to follow-up between groups, relative risk 0.30 (95% CI 0.05 to 1.94). From the trial data, when doctors initiated therapy and nurses provided follow-up, there was moderate quality evidence that there is probably no difference in death compared with doctor-led care at one year, relative risk of 0.89 (95% CI 0.59 to 1.32), two trials, cluster adjusted n = 4332. There was moderate quality evidence that there is probably no difference in the numbers of patients lost to follow-up at one year, relative risk 1.27 (95% CI 0.92 to 1.77), P = 0.15. From the cohort data, there is very low quality data that death at one year may be lower in the task shifting group, relative risk 0.19 (95% CI 0.05 to 0.78), one cohort, n = 2772, and very low quality evidence that loss to follow-up was reduced, relative risk 0.34 (95% CI 0.18 to 0.66). From the trial data, for maintenance therapy delivered in the community there was moderate quality evidence that there is probably no difference in mortality when doctors deliver care in the hospital or specially trained field workers provide home-based maintenance care and antiretroviral therapy at one year, relative risk 1.0 (95% CI 0.62 to 1.62), 1 trial, cluster adjusted n = 559. There is moderate quality evidence from this trial that losses to follow-up are probably no different at one year, relative risk 0.52 (0.12 to 2.3), P = 0.39. The cohort studies did not report on one year follow-up for these outcomes. Across the studies that reported on virological and immunological outcomes, there was no clear evidence of difference whether a doctor or nurse or clinical officer delivered therapy. Three studies report on costs to patients, indicating a reduction in travel costs to treatment facilities where task shifting was occurring closer to patients homes. There is conflicting evidence regarding the relative cost to the health system, as implementation of the strategy may increase costs. The two studies reporting the patient and staff perceptions of the quality of care, report good acceptability of the service by patients, and general acceptance by doctors of the shifting of roles. One trial reported on the time to initiation of antiretroviral therapy, finding no clear evidence of a difference between groups. The same trial reports on new diagnosis of tuberculosis which favours nurse initiation of HIV care for increasing the numbers of diagnoses of tuberculosis made. Our review found moderate quality evidence that shifting responsibility from doctors to adequately trained and supported nurses or community health workers for managing HIV patients probably does not decrease the quality of care and, in the case of nurse initiated care, may decrease the numbers of patients lost to follow-up.

We searched for studies up to March 2014. We found 10 studies, including four randomised controlled trials and 6 cohort studies collecting data from HIV care programmes. All the studies were conducted in Africa in adults who were followed up for up to one year. We describe three types of care: - Doctor versus nurse or clinical officer care for initiation and maintenance of antiretrovirals - Doctor versus nurse or clinical officer care for maintenance of antiretroviral therapy - Doctor versus community health workers for maintenance of antiretroviral therapy. We found high quality evidence from trial data that when nurses initiated and provided follow-up HIV therapy, there was no difference in death and lower rates of losses to follow up at one year, (n = 2770). However, lower quality data from two cohort studies suggests that there may be an increased risk of death in the task shifting group, (n = 39 160) but no difference in patients lost to follow-up between groups, We found moderate quality evidence from two trials that when doctors initiated therapy and nurses provided follow-up, that there was probably no difference in death or number of patients lost to follow up at one year (n = 4332). Lower quality evidence from the cohort study showed that death as well as the number of patients lost to follow-up at one year may be lower in the group treated by nurses. Compared to doctor led care, we found moderate quality evidence from a single trial that when antiretroviral therapy was provided in the community, by trained field workers, there was probably no difference in death or losses to follow-up (n= 559).

10.1002/14651858.CD007331.pub3

cochrane-simplification-train-3324

cochrane-simplification-train-3324

Completed randomised trials were not found. There is one trial that is currently ongoing in Italy; the results have yet to be published. Two prospective observational studies had data on recurrence-free survival. One study reported an odds ratio for recurrence rate at one year (where > 1 favours the luteal phase) of 0.86 (95% confidence interval (CI) 0.69 to 1.08); 0.87 at two years (95% CI 0.69 to 1.09); 0.95 at three years (95% CI 0.75 to 1.21); 1.12 at four years (95% CI 0.87 to 1.43); and 1.12 at five years (95% CI 0.87 to 1.43). Another study reported a hazard ratio for overall survival of 1.02 (95% CI 0.995 to 1.04, P = 0.14) and for disease-free survival of 1.00 (95% CI 0.98 to 1.02, P = 0.92) at three years based on the last and first menstrual period. The results were not significant. There was no difference in the recurrence rate whether the surgery was done during the follicular or luteal phase of the menstrual cycle. In the absence of RCTs, this review provides evidence from large prospective observational studies that timing of surgery does not show a significant effect on survival.

Of the three prospective observational studies, one reported no survival differences between menstrual cycle groups after stratification by lymph node status at a mean follow-up of 48 months. The results showed a lack of prognostic value (recurrence-free survival and overall survival) of timing of surgery in relation to the menstrual period or to oestrogen and progesterone levels in premenopausal breast carcinoma patients. One study gave no data on mean survival time or recurrence-free survival and the third study reported no significant difference in the overall survival of patients when surgery was done in either the follicular or luteal phase of the menstrual cycle. A large randomised controlled trial would be ideal to establish the influence of timing of surgery in relation to the menstrual cycle (follicular phase or luteal phase) on the prognosis of breast cancer. However, in the absence of this, the information available from the prospective observational studies shows that there is no difference in disease-free survival and overall survival in non-metastatic breast cancer patients irrespective of whether the surgery was done during the follicular or the luteal phase.

10.1002/14651858.CD003720.pub2

cochrane-simplification-train-3325

cochrane-simplification-train-3325

As of July 2017, we identified four trials with 192 participants that met the review inclusion criteria. Participating parents were mostly mothers (seven fathers were included in two studies), and children's ages ranged from one month to six years and five months. One study was conducted in Australia, one in Canada, one in the Netherlands, and one in the USA. Each studied a different intervention and considered different outcomes. Three interventions were delivered at home, and one in a community venue (e.g. a church). Interventions varied in duration from seven weeks to 12 months. They included a range of practical childcare skills, home safety and developing parents' ability to respond sensitively to their children. Parents in the comparison groups included in the review received treatment as usual and most of these received the index intervention after the study was complete. One study was funded by the Ontario Mental Health Foundation and the Ontario Ministry of Community and Social Services Research Grants Program; one by the Alabama Development Disabilities Council; one by the Best Practice Parenting Education Initiative of the Commonwealth Department of Family and Community Services and the New South Wales Aging and Disability Department; and one by ZonMw, The Netherlands Organisation for Health Research and Development. It was not possible for us to conduct a meta-analysis. The GRADE quality assessment varied from very low to moderate across the studies. Primary outcomes No study reported on the 'attainment of specific parenting skill targets'. 'Safe home practices' and 'understanding of child health': one study (30 parents, very low-quality evidence) reported some improvements in parents' knowledge of life-threatening emergencies, ability to recognise dangers, and identify precautions, in favour of the intervention group. It also found limited, very low-quality evidence that parent training improved parents' ability to understand child health, implement precautions, use medicines safely, recognise child illness and symptoms, and seek medical advice (i.e. visit the doctor). Another study (22 mothers, very low-quality evidence) reported improved attainment of skills related to childcare and safety, in favour of the intervention group. Secondary outcomes 'Parent-child interaction': one study (40 mothers, very low-quality evidence) reported improved maternal-child interaction following parent training at 12 months follow-up. Another study (83 mothers, 2 fathers, moderate-quality evidence) reported that inclusion in the intervention group led to a steeper decline in parenting stress related to the child compared to the control group. 'Parents' retention of child': one study (22 participants; very low-quality evidence) reported that before joining the programme nine of 11 (82%) families with a previous child had had the child removed from their care by child protection authorities due to maternal maltreatment, compared with only four of 22 (19%) families after participating in the programme (only one of these four mothers had also had a previous child removed). No study reported data on: 'return to independent care of child' or 'lifting of child-related court order'. There is some very low-quality evidence that some parents, mainly mothers, with intellectual disabilities are able to provide adequate parenting if they are given appropriate training and support to learn the parenting skills they need. However, there are few studies exploring how interventions might work, for whom and in what circumstances. In particular, there have been few studies that include fathers with intellectual disabilities, or that explore the views of parents themselves. There is a need for larger RCTs of parenting interventions, with longer follow-up, before conclusions can be drawn about the effectiveness of parent training for this group of parents.

The four RCTs were conducted in Australia, Canada, the Netherlands and USA, and involved 192 parents. Each studied a different intervention and considered different outcomes. All but seven of the participating parents were mothers. Children's ages ranged from one month to six years and five months. Three interventions were delivered at home, and one in a community venue (e.g. a church). Interventions varied in duration from seven weeks to 12 months. They included a range of practical childcare skills, home safety and developing parents' ability to respond sensitively to their children. Parents in the control groups all received treatment as usual. Each study was sponsored by different funders. One study was funded by the Ontario Mental Health Foundation and the Ontario Ministry of Community and Social Services Research Grants Program. Another was funded by the Alabama Development Disabilities Council. A third was funded by the Best Practice Parenting Education Initiative of the Commonwealth Department of Family and Community Services and the New South Wales Aging and Disability Department. The fourth study was funded by ZonMw, The Netherlands Organisation for Health Research and Development. Compared to those parents without parent training, the studies reported some improvements in parents in the intervention group. One study reported improvement in safe home practices, recognition of child illness and safe use of medicines, in favour of the intervention group. Another study reported improvements in childcare and safety, also in favour of the intervention group; and a third study found that parents who had attended parent training reported less child-related parenting stress compared to the control group. A fourth study reported improvement in mother-child interaction in the intervention group compared with the control group. No study reported that interventions caused harm. The quality of the evidence ranged from very low to moderate. There is some low-quality evidence that parent training interventions for parents with intellectual disabilities may support their parenting. It may also help to establish good parent-child relations. However, given the low quality of the evidence, the results should be interpreted with caution. Better-quality research is needed to evaluate the effectiveness of parent training interventions for parents with intellectual disabilities. These studies should include fathers and follow-up participants over a longer time period.

10.1002/14651858.CD007987.pub3

cochrane-simplification-train-3326

cochrane-simplification-train-3326

We included three RCTs in this review. It was unclear if the RCTs were three separate studies involving 1199 participants in total, or if they were reports from the same study involving fewer participants. We decided to treat the studies separately, as we were unable to make contact with the study authors to clarify. All three RCTs are of very low study quality because of issues with unclear randomization methods, allocation concealment and uncertainty of effect size. Some of the studies were reported as abstracts only and contained limited data, which prevented meaningful analysis and assessment of potential biases. The studies included participants who all received automated electronic monitoring during their hospital stay. Participants were randomized to an intervention group (automated alerts sent from the system) or to usual care (no automated alerts sent from the system). Evidence from all three studies reported 'Time to initiation of antimicrobial therapy'. We were unable to pool the data, but the largest study involving 680 participants reported median time to initiation of antimicrobial therapy in the intervention group of 5.6 hours (interquartile range (IQR) 2.3 to 19.7) in the intervention group (n = not stated) and 7.8 hours (IQR 2.5 to 33.1) in the control group (n = not stated). No studies reported 'Time to initiation of fluid resuscitation' or the adverse event 'Mortality at 30 days'. However very low-quality evidence was available where mortality was reported at other time points. One study involving 77 participants reported 14-day mortality of 20% in the intervention group and 21% in the control group (numerator and denominator not stated). One study involving 442 participants reported mortality at 28 days, or discharge was 14% in the intervention group and 10% in the control group (numerator and denominator not reported). Sample sizes were not reported adequately for these outcomes and so we could not estimate confidence intervals. Very low-quality evidence from one study involving 442 participants reported 'Length of stay in ICU'. Median length of stay was 3.0 days in the intervention group (IQR = 2.0 to 5.0), and 3.0 days (IQR 2.0 to 4.0 in the control). Very low-quality evidence from one study involving at least 442 participants reported the adverse effect 'Failed detection of sepsis'. Data were only reported for failed detection of sepsis in two participants and it wasn't clear which group(s) this outcome occurred in. No studies reported 'Quality of life'. It is unclear what effect automated systems for monitoring sepsis have on any of the outcomes included in this review. Very low-quality evidence is only available on automated alerts, which is only one component of automated monitoring systems. It is uncertain whether such systems can replace regular, careful review of the patient's condition by experienced healthcare staff.

We conducted a search to identify evidence published before September 2017. Studies were eligible for inclusion if they compared automated sepsis monitoring to standard care (such as paper-based systems) in people admitted to intensive or critical care units for critical illness. We did not include non-randomized studies (studies where participants were not allocated to treatment groups by chance), quasi-randomized studies (studies where participants were allocated to treatment groups by a method that is not truly down to chance, such as date of birth or medical number), and cross-over studies (where participants first receive one treatment and then cross over to receive the other treatment). Studies including people already diagnosed with sepsis were also excluded. We included three randomized controlled trials (studies where participants were allocated to treatment groups by chance), involving 1199 participants in this review. Overall there were no significant differences in time to start of antimicrobial therapy (such as antimicrobial and antifungal treatments, very low-quality evidence), length of stay in the intensive care setting (very low-quality evidence), or in mortality at 14 days, 28 days or discharge (very low-quality evidence) when automated monitoring systems were compared to standard care. Very low-quality evidence was available on failed detection of sepsis but data reporting was too unclear to enable us to analyse this in a meaningful way. Other outcomes that we wished to assess like time to initiation of fluid resuscitation (the process of increasing the amount of fluids in the body), mortality at 30 days, and quality of life were not reported in any of the studies. Results of this review show limited, very low-quality evidence, which has prevented us from drawing meaningful conclusions. It is unclear what effect automated systems for monitoring sepsis have on any outcomes included in this review, and therefore we are uncertain if automated sepsis monitoring is beneficial or not. Additional, high-quality evidence is needed to help address our review question.

10.1002/14651858.CD012404.pub2

cochrane-simplification-train-3327

cochrane-simplification-train-3327

Five studies treated 168 participants with painful diabetic neuropathy or polyneuropathy. The mean age in individual studies was between 47 and 56 years. Four studies used a cross-over, and one a parallel group design; 126 participants were randomised to receive imipramine 25 mg to 350 mg daily (most took 100 mg to 150 mg daily). Comparators were placebo (an active placebo in one study), paroxetine, mianserin, venlafaxine, and amitriptyline, and treatment was given for 2 to 12 weeks. All studies had one or more sources of potential major bias. No study provided first or second tier evidence for any outcome. No data were available on the proportion of people with at least 50% or 30% reduction in pain or equivalent, and data were available from only one study for our other primary outcome of Patient Global Impression of Change, reported as patient evaluation of pain relief of complete or good. No pooling of data was possible, but third tier evidence in individual studies indicated some improvement in pain relief with imipramine compared with placebo, although this is was very low quality evidence, derived mainly from group mean data and completer analyses, in small, short duration studies where major bias is possible. Four studies reported some information about adverse events, but reporting was inconsistent and fragmented, and the quality of evidence was very low. Participants taking imipramine generally experienced more adverse events, notably dry mouth, and a higher rate of withdrawal due to adverse events, than did participants taking placebo. This review found little evidence to support the use of imipramine to treat neuropathic pain. There was very low quality evidence of benefit but this came from studies that were methodologically flawed and potentially subject to major bias. Effective medicines with much greater supportive evidence are available.

We found five studies involving 168 participants with painful diabetic neuropathy or polyneuropathy. Studies were randomised and double-blind, but all had one or more sources of potential major bias that could lead to overestimation of efficacy. It was not possible to combine information from the different studies, but individually they indicated some benefit from imipramine (usually at a dose between 100 mg and 150 mg daily) compared with placebo, at the expense of increased adverse events. There was too little information, which was of inadequate quality, to be sure that imipramine works as a pain medicine in neuropathic pain due to diabetes or due to damage to multiple nerves. There was no information about other types of neuropathic pain. Other medicines have been shown to be effective.

10.1002/14651858.CD010769.pub2

cochrane-simplification-train-3328

cochrane-simplification-train-3328

We identified three studies as eligible for inclusion in the review. Two were in the previous review and one new study was included. We considered the older studies to be at high or unclear risk of bias whereas we judged the newly included study at low risk of bias. The studies varied in treatment duration (from 7 to 14 days) and the antibiotic used (two studies used amoxicillin/clavulanate acid and one used erythromycin). We included 190 children (171 completed), mean ages ranged from 21 months to six years, in the meta-analyses. Analysis of all three trials (190 children) found that treatment with antibiotics reduced the proportion of children not cured at follow-up (primary outcome measure) (odds ratio (OR) 0.15, 95% confidence interval (CI) 0.07 to 0.31, using intention-to -treat analysis), which translated to a number needed to treat for an additional beneficial outcome (NNTB) of 3 (95% CI 2 to 4). We identified no significant heterogeneity (for both fixed-effect and random-effects model the I² statistic was 0%). Two older trials assessed progression of illness, defined by requirement for further antibiotics (125 children), which was significantly lower in the antibiotic group (OR 0.10, 95% CI 0.03 to 0.34; NNTB 4, 95% CI 3 to 5). All three trials (190 children) reported adverse events, which were not significantly increased in the antibiotic group compared to the control group (OR 1.88, 95% CI 0.62 to 5.69). We assessed the quality of evidence GRADE rating as moderate for all outcome measures, except adverse events which we assessed as low quality. Evidence suggests antibiotics are efficacious for the treatment of children with chronic wet cough (greater than four weeks) with an NNTB of three. However, antibiotics have adverse effects and this review reported only uncertainty as to the risk of increased adverse effects when they were used in this setting. The inclusion of a more robust study strengthened the previous Cochrane review and its results.

We included randomised controlled trials that compared antibiotics with a placebo (pretend treatment) or control group. The children included in the trials had wet cough lasting more than 10 days. The evidence is current to September 2017. We found three studies that varied in a number of ways including different antibiotics (two studies used amoxicillin/clavulanate acid and one used erythromycin) and length of treatment was seven or 14 days. The mean ages of the children ranged from 21 months to six years. This review, involving 190 children with persistent wet cough, found that antibiotics were beneficial in curing the cough. The cure rate was one child cured for every three children treated. Antibiotics also prevented the illness from getting worse, thus avoiding a further course of antibiotics, for one in every four children treated. We found no clear evidence about whether antibiotics were associated with more side effects. We could not assess long-term results. The reliability of the evidence was moderate when using antibiotics to cure cough and for illness progression, while it was only low for side effects of medicines. Antibiotics are effective in treating children with chronic (greater than four weeks) wet cough and could be considered when they present to doctors.

10.1002/14651858.CD004822.pub3

cochrane-simplification-train-3329

cochrane-simplification-train-3329

We included 15 studies, involving over 2000 women. Antibiotic treatment compared with placebo or no treatment may reduce the incidence of pyelonephritis (average risk ratio (RR) 0.24, 95% confidence interval (CI) 0.13 to 0.41; 12 studies, 2017 women; low-certainty evidence). Antibiotic treatment may be associated with a reduction in the incidence of preterm birth (RR 0.34, 95% CI 0.13 to 0.88; 3 studies, 327 women; low-certainty evidence), and low birthweight babies (average RR 0.64, 95% CI 0.45 to 0.93; 6 studies, 1437 babies; low-certainty evidence). There may be a reduction in persistent bacteriuria at the time of delivery (average RR 0.30, 95% CI 0.18 to 0.53; 4 studies; 596 women), but the results were inconclusive for serious adverse neonatal outcomes (average RR 0.64, 95% CI 0.23 to 1.79, 3 studies; 549 babies). There were very limited data on which to estimate the effect of antibiotics on other infant outcomes, and maternal adverse effects were rarely described. Overall, we judged only one trial at low risk of bias across all domains; the other 14 studies were assessed as high or unclear risk of bias. Many studies lacked an adequate description of methods, and we could only judge the risk of bias as unclear, but in most studies, we assessed at least one domain at high risk of bias. We assessed the quality of the evidence for the three primary outcomes with GRADE software, and found low-certainty evidence for pyelonephritis, preterm birth, and birthweight less than 2500 g. Antibiotic treatment may be effective in reducing the risk of pyelonephritis in pregnancy, but our confidence in the effect estimate is limited given the low certainty of the evidence. There may be a reduction in preterm birth and low birthweight with antibiotic treatment, consistent with theories about the role of infection in adverse pregnancy outcomes, but again, the confidence in the effect is limited given the low certainty of the evidence. Research implications identified in this review include the need for an up-to-date cost-effectiveness evaluation of diagnostic algorithms, and more evidence to learn whether there is a low-risk group of women who are unlikely to benefit from treatment of asymptomatic bacteriuria.

We found 15 randomised controlled studies involving over 2000 pregnant women with urinary infections, but no symptoms. Antibiotics may be effective in reducing the incidence of kidney infection in the mother (12 studies, 2017 women) and clearing the infection from the urine (four studies, 596 women). They may also reduce the incidence of preterm births (three studies, 327 women) and low birthweight babies (six studies, 1437 babies). None of the studies adequately assessed any adverse effects of antibiotic treatment for the mother or her baby, and often the way the study was done was not well described. We assessed the three main outcomes with the GRADE approach, and found low-certainty evidence that antibiotic treatment may prevent pyelonephritis, preterm birth, and birthweight less than 2500 g. Antibiotic treatment may reduce the risk of kidney infections in pregnant women who have a urine infection but show no symptoms of infection. Antibiotics may also reduce the chance a baby will be born too early or have a low birthweight. However, because of the low certainty of the evidence, it is difficult to draw conclusions; more research is needed.

10.1002/14651858.CD000490.pub4

cochrane-simplification-train-3330

cochrane-simplification-train-3330

We included 14 studies (7 case-control and 7 cohort studies). These examined oral contraceptives (OCs), depot medroxyprogesterone acetate (DMPA), and the hormonal intrauterine device (IUD). This section focuses on the sensitivity analysis with six studies that provided moderate or high quality evidence. All six studies examined oral contraceptive use. We noted few associations with fracture risk. One cohort study reported OC ever-users had increased risk for all fractures (RR 1.20, 95% CI 1.08 to 1.34). However, a case-control study with later data from a subset reported no association except for those with 10 years or more since use (OR 1.55, 95% CI 1.03 to 2.33). Another case-control study reported increased risk only for those who had 10 or more prescriptions (OR 1.09, 95% CI 1.03 to 1.16). A cohort study of postmenopausal women found no increased fracture risk for OC use after excluding women with prior fracture. Two other studies found little evidence of association between OC use and fracture risk. A cohort study noted increased risk for subgroups, such as those with longer use or specific intervals since use. A case-control study reported increased risk for any fracture only among young women with less than average use. Two case-control studies also examined progestin-only contraceptives. One reported increased fracture risk for DMPA ever-use (OR 1.44, 95% CI 1.01 to 2.06), more than four years of use (OR 2.16, 95% CI 1.32 to 3.53), and women over 50 years old. The other reported increased risk for any past use, including one or two prescriptions (OR 1.17, 95% CI 1.07 to 1.29) and for current use of 3 to 9 prescriptions (OR 1.36, 95% CI 1.15 to 1.60) or 10 or more (OR 1.54, 95% CI 1.33 to 1.78). For the levonorgestrel-releasing IUD, one study reported reduced fracture risk for ever-use (OR 0.75, 95% CI 0.64 to 0.87) and for longer use. Observational studies do not indicate an overall association between oral contraceptive use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Investigators should be clear about the variables examined in multivariate analysis.

We included studies that looked at hormonal birth control use and fracture risk. We examined the quality of research methods using a tool for observational studies. With these types of studies, investigators need to control for differences in the study groups. We used the results from adjusted analyses as reported. Where we did not have adjusted analysis, we used the odds ratio to look at differences between groups. We found 14 studies. Six of them had good quality results and looked at use of birth control pills. We did not find an overall difference in fracture risk for users and nonusers of birth control pills. One study found pill users were more likely to have fractures overall. Another had later data for a subset of those women. Pill use was not related to fracture risk except for 10 or more years since use. Still another study showed more risk when the woman had 10 or more prescriptions. When a study of postmenopausal women removed the women with prior fracture, pill users did not have higher fracture risk. Two more studies saw more fractures in pill users but only for certain subgroups. Two studies looked at birth control methods that contain only the hormone progestin. They found that users of the injected ‘depo’ (depot medroxyprogesterone acetate) had more fractures as did women with longer current use. One showed more fractures for women with any past 'depo' use. Another study showed that women who had used the hormonal intrauterine device (IUD) were less likely to have a fracture. These studies did not show that birth control pills are generally related to more fractures. Some studies reported greater risk for subgroups. Users of ‘depo’ may have more fracture risk. Observational studies need to examine differences between study groups. Investigators should be clear about the factors studied in the analysis.

10.1002/14651858.CD009849.pub3

cochrane-simplification-train-3331

cochrane-simplification-train-3331

We found six trials (542 participants) that met our inclusion criteria. These trials assessed the effectiveness of hormonal therapy in women with advanced or recurrent endometrial cancer as a single agent, as part of combination therapy and as low versus high dose. All comparisons were restricted to single-trial analyses, where we found no evidence that hormonal therapy as a single agent or as a combination treatment prolonged overall or five-year disease-free survival of women with advanced or recurrent endometrial cancer. However, low-dose hormonal therapy may have had a benefit in terms of overall and progression-free survival (PFS) compared to high-dose hormonal therapy (HR 1.31, 95% CI 1.04 to 1.66 and HR 1.35, 95% CI 1.07 to 1.71 for overall and PFS, respectively). We found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy improves the survival of patients with advanced or recurrent endometrial cancer. However, a large number of patients would be needed to demonstrate an effect on survival and none of the included RCTs had a sufficient number of patients to demonstrate a significant difference. In the absence of a proven survival advantage and the heterogeneity of patient populations, the decision to use any type of hormonal therapy should be individualised and with the intent to palliate the disease. It is debatable whether outcomes such as quality of life, treatment response or palliative measures such as relieving symptoms should take preference over overall and PFS as the major objectives of future trials.

Endometrial cancer is cancer arising from the lining of the womb. Most women with endometrial cancer are diagnosed when their tumour is still confined to the body of the womb. However, about 10% of women with endometrial cancer are diagnosed when the disease is already at an advanced stage. The latter group of patients tend to have much poorer survival. Treatment of women with advanced or recurrent endometrial cancer is challenging because often they suffer from other diseases and aggressive chemotherapy with or without surgery may not be beneficial or may even be harmful. Hormonal therapy in these cases is thought to be easily administered and to cause fewer side effects than systemic chemotherapy (standard treatment). The purpose of this review was to assess the available literature on the effect of hormonal treatment on the survival of patients with advanced or recurrent endometrial cancer. We found six randomised controlled trials (RCTs) that assessed hormonal treatment in various forms and combinations in 542 eligible patients. We found insufficient evidence to suggest that hormonal therapy improves survival in these patients. The main limitations of the review were the small number of patients included in the RCTs, the diversity of both the patient population and the hormonal agents used and the fact that quality of life was not reported in any of the trials. The quality of life with treatment is especially important for a condition that has a poor survival rate.

10.1002/14651858.CD007926.pub2

cochrane-simplification-train-3332

cochrane-simplification-train-3332

A total of 32 trials provided data for inclusion in the review in terms of efficacy, withdrawal and side effect analysis. We were unable to find any differences in efficacy when comparing classes of antidepressants. Tricyclic antidepressants (TCAs) compared less favourably with selective serotonin reuptake inhibitors (SSRIs) in terms of numbers of patients withdrawn irrespective of reason (RR: 1.23, CI 1.05 to 1.43) and number withdrawn due to side effects (RR: 1.36, CI 1.09 to 1.70). Further analyses demonstrated that TCA related antidepressants had similar withdrawal rates to SSRIs irrespective of reason of withdrawal (RR: 1.49, CI 0.74 to 2.98) or withdrawal due to side effects (RR: 1.07, CI 0.43 to 2.70). The qualitative analysis of side effects showed a small increased profile of gastro-intestinal and neuropsychiatric side effects associated with classical TCAs. Our findings suggest that SSRIs and TCAs are of the same efficacy. However, we have found some evidence suggesting that TCA related antidepressants and classical TCAs have different side effect profiles and are associated with differing withdrawal rates when compared with SSRIs. The review suggests that classical TCAs are associated with a higher withdrawal rate due to side effect experience, although these results must be interpreted with caution due to the heterogeneity of the drugs and patient populations.

This review compared the efficacy, withdrawal rates and side effects of different antidepressant classes in the treatment of depression in older people. Thirty-two studies provided data for the review. Our main findings indicate that tricyclic antidepressants (classical and tricyclic related) and selective serotonin reuptake inhibitors (SSRIs) are equally efficacious. However, when comparing the two tricyclic groups with SSRIs we found that tricyclic related antidepressants were similar to SSRIs in terms of overall withdrawal rate, and classical tricyclic antidepressants were associated with a higher withdrawal rate due to side effects. These findings are reflected in the differing side effect profiles when comparing both tricyclic groups with SSRIs. The findings of the review must be interpreted with some caution in view of the relatively low patient numbers and lack of side effect data.

10.1002/14651858.CD003491.pub2

cochrane-simplification-train-3333

cochrane-simplification-train-3333

We included three quasi-randomised controlled trials, with a total of 149 women and their babies. All three trials were at a high risk of bias. When comparing women receiving relaxin with those who did not receive relaxin, there was a significant reduction in birth within seven days of treatment in one trial of 30 women (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.29 to 0.87), yet no significant difference was seen for perinatal mortality in this trial (RR 0.83, 95% CI 0.32 to 2.15). The second and third included trials did not report on any of the primary outcomes pre-specified in the review, including birth within 48 hours of treatment, birth within seven days of treatment, perinatal mortality, and serious neonatal adverse outcomes. One trial found a significant increase in pregnancy prolongation for women receiving relaxin (RR 8.00, 95% CI 1.14 to 56.33; 30 women). None of the three included trials found significant differences in the outcomes of fetal death, neonatal death, birthweight or preterm birth, and no trial reported on longer-term outcomes for the babies. There is limited randomised controlled trial evidence available on the effect of relaxin during pregnancy for preventing preterm birth for women in preterm labour. Evidence from one quasi-randomised trial suggested a reduction in birth within seven days of treatment for women receiving relaxin, compared with women in a control group, however this trial was at a high risk of bias and included only 30 women. There is thus insufficient evidence to support or refute the use of relaxin in women in preterm labour for preventing preterm birth.

We included three small randomised trials involving 149 women in preterm labour in the review. These trials were conducted in the 1950s and had a high risk of bias overall. We found no convincing evidence that relaxin (given by intravenous and intramuscular injection) can prevent preterm birth for women in preterm labour. Only one of the studies, involving 30 women (and at a high risk of bias), reported on birth within seven days of treatment and found that women who received relaxin were less likely to give birth preterm within seven days of treatment, and were more likely to have a longer pregnancy than women who did not receive relaxin. The risk of babies dying was not significantly different between the women who received relaxin and those who did not. Neither of the other two trials found clear differences in preterm birth, and no trial reported on longer-term outcomes for the babies. There is therefore insufficient evidence from this review to recommend relaxin as an intervention to prevent preterm birth for women in preterm labour.

10.1002/14651858.CD010073.pub2

cochrane-simplification-train-3334

cochrane-simplification-train-3334

We included 38 studies (3679 women). Nine studies included pregnancies after intrauterine deaths, five studies included termination of pregnancies because of fetal anomalies when the fetus was still alive and the rest (24) presented the pooled data for intrauterine deaths, fetal anomalies and social reasons. When compared with agents that have traditionally been used to induce labour in this setting (for example, gemeprost, prostaglandin E2 and prostaglandin F2alpha), vaginal misoprostol is as effective in ensuring vaginal birth within 24 hours, with a similar induction to birth interval. Vaginal misoprostol is associated with a reduction in the occurrence of maternal gastrointestinal side effects such as nausea, vomiting and diarrhoea when compared with other prostaglandin preparations. While the different treatments involving various prostaglandin preparations appear comparable for the reported outcomes, the information available regarding rare maternal complications, such as uterine rupture, is limited. The use of vaginal misoprostol in the termination of second and third trimester of pregnancy is as effective as other prostaglandin preparations (including cervagem, prostaglandin E2 and prostaglandin F2alpha), and more effective than oral administration of misoprostol. However, important information regarding maternal safety, and in particular the occurrence of rare outcomes such as uterine rupture, remains limited. Future research efforts should be directed towards determining the optimal dose and frequency of administration, with particular attention to standardised reporting of all relevant outcomes and assessment of rare adverse events. Further information is required about the use of sublingual misoprostol in this setting.

This review included 38 randomised controlled studies, involving 3679 women. Vaginal misoprostol was as effective as other agents in inducing labour and achieving vaginal birth within 24 hours, with a reduction in the occurrence of maternal side effects. Side effects include gastrointestinal disturbance (nausea, vomiting, diarrhoea). The information on rare adverse events (including uterine rupture) is limited.

10.1002/14651858.CD004901.pub2

cochrane-simplification-train-3335

cochrane-simplification-train-3335

Our search strategy yielded 2696 references. Two review authors independently assessed all references for inclusion. Two randomized controlled trials, for a total of 110 infants, met the inclusion criteria of this review. Both trials compared supine midline head position with the bed at 0° versus supine head rotated 90° with the bed at 0°. We found no trials that compared supine versus prone midline head position, and no trials that compared effects of head tilting. We found no significant differences in rates of GM-IVH (typical risk ratio [RR] 1.14, 95% confidence interval [CI] 0.55 to 2.35; typical risk difference [RD] 0.03, 95% CI -0.13 to 0.18; two studies, 110 infants; I2 = 0% for RR and I2 = 0% for RD), severe IVH (typical RR 1.57, 95% CI 0.28 to 8.98; typical RD 0.02, 95% CI -0.06 to 0.10; two studies, 110 infants; I2 = 0% for RR and I2 = 0% for RD), and neonatal mortality (typical RR 0.52, 95% CI 0.16 to 1.65; typical RD -0.07, 95% CI -0.18 to 0.05; two studies, 110 infants; I2 = 28% for RR and I2 = 44% for RD). Among secondary outcomes, we found no significant differences in terms of cystic periventricular leukomalacia (one study; RR 3.25, 95% CI 0.14 to 76.01; RD 0.04, 95% CI -0.07 to 0.15), retinopathy of prematurity (one study; RR 2.27, 95% CI 0.85 to 6.11; RD 0.25, 95% CI -0.02 to 0.53), and severe retinopathy of prematurity (one study; RR 2.73, 95% CI 0.31 to 24.14; RD 0.09, 95% CI -0.09 to 0.26). None of the included trials reported on the other specified outcomes of this review (i.e., cerebellar hemorrhage, brain magnetic resonance imaging abnormalities, impairment in cerebral hemodynamics, long-term neurodevelopmental outcomes, and major neurodevelopmental disability). The quality of evidence supporting these findings is limited owing to the imprecision of the estimates. We identified no ongoing studies. Given the imprecision of the estimate, results of this systematic review are consistent with beneficial or detrimental effects of a supine head midline position versus a lateral position and do not provide a definitive answer to the review question.

We included two studies comparing supine midline head position versus supine head rotated 90°. This review of trials found too little evidence to show positive or negative effects of supine (lying on the back) midline head position for prevention of intraventricular hemorrhage (i.e., bleeding within the brain), mortality, or any other relevant outcomes in very preterm neonates. More research is needed. We found no trials that compared supine (lying on the back) versus prone (lying on the stomach) midline head position, and no trials that compared effects of head tilting (elevating the head of the incubator upward). Results of this systematic review are consistent with beneficial or detrimental effects of a supine head midline position and do not provide a definitive answer to the review question.

10.1002/14651858.CD012362.pub2

cochrane-simplification-train-3336

cochrane-simplification-train-3336

Brynskov 1989a found that patients receiving high dose cyclosporine (median 7.6 mg/kg/day) had statistically significant clinical improvement at 12 weeks compared to placebo patients. None of the other studies found any statistically significant benefit for clinical improvement or induction of remission for low dose cyclosporine treatment (5 mg/kg/day) used by itself or in combination with corticosteroids compared to placebo. Cyclosporine was associated with a significantly higher proportion of adverse events and withdrawals due to adverse events relative to placebo. Brynskov 1989a enrolled a small number of patients and the modified clinical grading scale used in the study has not been validated in other studies. Furthermore, statistically significant clinical improvement does not imply induction of clinical remission. Indeed, Brynskov 1989a found no statistically significant differences in the mean Crohn's Disease Activity Index score at 12 weeks indicating that cyclosporine was no more effective than placebo for induction of remission in Crohn's disease. The results of this review demonstrate that low dose (5 mg/kg/day) oral cyclosporine is not effective for the induction of remission in Crohn's disease. Patients treated with low dose oral cyclosporine are more likely than placebo treated patients to experience adverse events including renal dysfunction. The use of low dose oral cyclosporine for the treatment of chronic active Crohn's disease does not appear to be justified. Oral dosing at higher levels or parenteral administration of cyclosporine have not been adequately evaluated in controlled clinical trials. Higher doses of cyclosporine are not likely to be useful for the long-term management of Crohn's disease because of the risk of nephrotoxicity and the availability of other proven interventions.

The results of this review demonstrate that low dose oral cyclosporine is not effective for treatment of active Crohn's disease. Studies indicate that Crohn's patients treated with low dose (5 mg/kg/day) oral cyclosporine could experience side effects including kidney problems. Therefore the use of this medication for the treatment of chronic active Crohn's disease is not advisable. Higher oral doses and injections of cyclosporine have not been sufficiently evaluated. Larger doses of cyclosporine are not likely to be useful for the long-term management of Crohn's disease due to the risk of kidney damage and the availability of other proven medications.

10.1002/14651858.CD000297.pub2

cochrane-simplification-train-3337

cochrane-simplification-train-3337

Nine studies were included representing 425 participants. All studies compared omega-3 fatty acid supplementation with placebo lasting from four weeks to two years. Three studies with long treatment periods administered additional substances, making any observed effects impossible to attribute to omega-3 fatty acids and were excluded from the statistical analyses. One study did not express any mean values and, therefore, could not be included in statistical analyses. No significant differences between intervention and control groups were observed in pain-free walking distance (mean difference (MD) 11.62 m, 95% confidence interval (CI) -67.74 to 90.98), maximal walking distance (MD 16.99 m, 95% CI -72.14 to 106.11), ankle brachial pressure index (MD -0.02, 95% CI -0.09 to 0.05), total cholesterol levels (MD 0.27 mmol/L, 95% CI -0.48 to 1.01), high-density lipoprotein cholesterol levels (MD 0.00 mmol/L, 95% CI -0.16 to 0.15), low-density lipoprotein cholesterol levels (MD 0.44 mmol/L, 95% CI -0.31 to 1.19), triglyceride levels (MD -0.39 mmol/L, 95% CI -1.10 to 0.33), systolic blood pressure (MD 5.00 mmHg, 95% CI -11.59 to 21.59) or plasma viscosity (MD 0.03 mPa/s, 95% CI -0.02 to 0.08). There was some limited evidence that blood but not plasma viscosity levels decreased with treatment and gastrointestinal side effects such as nausea, diarrhoea and flatulence were observed in two studies. Omega-3 fatty acids appear to have little haematological benefit in people with intermittent claudication and there is no evidence of consistently improved clinical outcomes (quality of life, walking distance, ankle brachial pressure index or angiographic findings). Supplementation may also cause adverse effects such as nausea, diarrhoea and flatulence. Further research is needed to evaluate fully short- and long-term effects of omega-3 fatty acids on the most clinically relevant outcomes in people with intermittent claudication before they can be recommended for routine use.

The review included nine randomised controlled trials with 425 participants, comparing omega-3 fatty acid supplementation with other fatty acids. On the basis of these studies, omega-3 fatty acid supplementation did not improve walking distance, blood pressure in the leg or any other measure of clinical benefit. There was some limited evidence to suggest that omega-3 fatty acid supplementation may reduce blood viscosity (the resistance of blood to flow), which when high could potentially contribute to intermittent claudication. There was no evidence to suggest that omega-3 fatty acid supplementation reduced plasma (the liquid component of blood) viscosity or improved the levels of different types of cholesterol or any other components of blood tested. Side effects such as nausea, diarrhoea and flatulence were observed in two studies.

10.1002/14651858.CD003833.pub4

cochrane-simplification-train-3338

cochrane-simplification-train-3338

We included two RCTs involving a total of 149 children between three months and 18 years of age who were receiving antibiotics for septic arthritis. The most commonly affected joints were hips and knees. These studies were performed in Costa Rica and Israel. In both studies, dexamethasone administered intravenously (ranging from 0.15 to 0.2 mg/kg/dose every six to eight hours) during four days was the corticosteroid, and the comparator was placebo. Trials excluded patients with any degree of immunodeficiency or immunosuppression. The longest follow-up was one year. Trials did not report activities of daily living nor length of hospital stay. Both studies used adequate processes for randomisation, allocation concealment, and blinding, and review authors judged them to have low risk of selection and performance bias. Losses to follow-up were substantive in both studies, and we judged them to have high risk of attrition bias and of selective outcome reporting. We graded all outcomes as low quality due to concerns about study limitations and imprecision. The risk ratio (RR) for absence of pain at 12 months of follow-up was 1.33, favouring corticosteroids (95% confidence interval (CI) 1.03 to 1.72; P = 0.03; number needed to treat for an additional beneficial outcome (NNTB) = 13, 95% CI 6 to 139; absolute risk difference 24%, 95% CI 5% to 43%). The RR for normal function of the affected joint at 12 months of follow-up was 1.32, favouring corticosteroids (95% CI 1.12 to 1.57; P = 0.001; NNTB = 13, 95% CI 7 to 33; absolute risk difference 24%, 95% CI 11% to 37%). We found a reduction in the number of days of intravenous antibiotic treatment favouring corticosteroids (mean difference (MD) -2.77, 95% CI -4.16 to -1.39) based on two trials with 149 participants. Researchers did not report length of hospital stay. One trial (49 participants) reported that treatment with dexamethasone was associated with a shorter duration of IV antibiotic treatment, leading to a shorter hospital stay, and although duration of hospitalisation was a primary outcome of the study, study authors did not provide data on the duration of hospitalisation. We downgraded the quality by one level for concerns about study limitations (high risk of attrition bias and selective reporting), and by another level for imprecision. In one trial of 49 participants, researchers followed 29 children for 12 months, and parents reported that no children demonstrated adverse effects of the intervention. Evidence for corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis is of low quality and is derived from the findings of two trials (N = 149). Corticosteroids may increase the proportion of patients without pain and the proportion of patients with normal function of the affected joint at 12 months, and may also reduce the number of days of antibiotic treatment. However, we cannot draw strong conclusions based upon these trial results. Additional randomised clinical trials in children with relevant outcomes are needed.

Researchers conducted a review of the effects of corticosteroids given in addition to antibiotics to children with septic arthritis. Evidence was sought until April 2018. After searching for all relevant studies, reviewers found two studies with 149 children. These studies were conducted in hospitalised children with a normal immune system between the ages of three months and 18 years living in Costa Rica and Israel. The longest follow-up was one year. Reviewer findings are summarised below. What is septic arthritis and what are corticosteroids? Septic arthritis, which is more frequent in children, is a serious disease caused by bacteria that infect the joints. Patients are usually treated with antibiotics, but secondary inflammation can destroy the joint and can reduce the ability of the joint to function normally. Corticosteroids are a group of medications with anti-inflammatory properties. Corticosteroids may reduce the consequences of inflammation in the joints. For children with septic arthritis who are taking antibiotics compared to placebo (fake medication) 1. Corticosteroids may reduce pain in affected joints at one year of follow-up 2. Corticosteroids may improve normal function of affected joints at one year of follow-up 3. Corticosteroids may reduce days of intravenous antibiotic treatment needed 4. Corticosteroids may have little or no effect on total or serious adverse effects We do not have information about the effects of corticosteroids on activities of daily living. What happens to children with septic arthritis who take corticosteroids in addition to antibiotics? Absence of pain 1. 24 more of 100 children experienced absence of pain after 12 months with corticosteroids (24% absolute improvement) 2. 96 of 100 children experienced absence of pain compared to 72 of 100 children who took a placebo Activities of daily living Included studies did not report this outcome. Normal physical joint function 1. 24 more of 100 children who received corticosteroids had normal function of the joint after 12 months (24% absolute improvement) 2. 98 of 100 children experienced absence of pain compared to 74 of 100 children who received a placebo Number of days of intravenous antibiotic treatment 1. Children who received corticosteroids compared with placebo had 2.77 fewer days of intravenous antibiotic treatment 2. Children who received corticosteroids had 8.09 days of intravenous antibiotic treatment 3. Children who received placebo had 10.86 days of intravenous antibiotic treatment Length of hospital stay 1. We are uncertain whether corticosteroids had an effect on the length of hospital stay because the evidence was of very low quality Total or serious adverse events 1. None of the patients treated with corticosteroids reported adverse effects at 12 months Quality of the evidence Overall, these studies provided low-quality evidence due to small numbers of study participants and concerns about study design. Evidence on length of hospital stay was of very low quality, as this was not clearly reported.

10.1002/14651858.CD012125.pub2

cochrane-simplification-train-3339

cochrane-simplification-train-3339

Fourteen studies with data from 672 participants met the inclusion criteria. Five different antiepileptic drugs were examined. Sodium valproate/divalproex was superior to placebo for outpatient men with recurrent impulsive aggression, for impulsively aggressive adults with cluster B personality disorders, and for youths with conduct disorder, but not for children and adolescents with pervasive developmental disorder. Carbamazepine was superior to placebo in reducing acts of self-directed aggression in women with borderline personality disorder, but not in children with conduct disorder. Oxcarbazepine was superior to placebo for verbal aggression and aggression against objects in adult outpatients. Phenytoin was superior to placebo on the frequency of aggressive acts in male prisoners and in outpatient men including those with personality disorder, but not on the frequency of 'behavioral incidents' in delinquent boys. The authors consider that the body of evidence summarised in this review is insufficient to allow any firm conclusion to be drawn about the use of antiepileptic medication in the treatment of aggression and associated impulsivity. Four antiepileptics (valproate/divalproex, carbamazepine, oxcarbazepine and phenytoin) were effective, compared to placebo, in reducing aggression in at least one study, although for three drugs (valproate, carbamazepine and phenytoin) at least one other study showed no statistically significant difference between treatment and control conditions. Side effects were more commonly noted for the intervention group although adverse effects were not well reported. Absence of information does not necessarily mean that the treatment is safe, nor that the potential gains from the medication necessarily balance the risk of an adverse event occurring. Further research is needed.

This review systematically examines the evidence supporting this practice. From the evidence available, we were unable to draw any firm conclusion about using these medicines to treat aggression. Four antiepileptic drugs (valproate/divalproex, carbamazepine, oxcarbazepine and phenytoin) helped to reduce aggression in at least one study. However, for three of these drugs (valproate, carbamazepine and phenytoin) we found at least one other study where there was no significant improvement. Further research is needed to clarify which antiepileptic drugs are effective for whom. Such research is best carried out using carefully designed clinical trials. Such trials need to take account of the type of aggression displayed, the severity of the aggression, and any other disorders experienced by the participants.

10.1002/14651858.CD003499.pub3

cochrane-simplification-train-3340

cochrane-simplification-train-3340

We identified four studies meeting our inclusion criteria. Overall, trials were of poor to moderate methodological quality. Few trial authors responded to our written inquiries seeking to resolve controversial issues and to obtain individual patient data. Strong heterogeneity amongst the trials prompted discussion between the review authors as to whether the data should or should not be pooled; we decided in favour of a quantitative synthesis to provide a rough impression about the effect sizes achievable with US-based triage algorithms. We pooled mortality data from three trials involving 1254 patients; the RR in favour of the FAST arm was 1.00 (95% CI 0.50 to 2.00). FAST-based pathways reduced the number of CT scans (random-effects model RD -0.52, 95% CI -0.83 to -0.21), but the meaning of this result was unclear. The experimental evidence justifying FAST-based clinical pathways in diagnosing patients with suspected abdominal or multiple blunt trauma remains poor. Because of strong heterogeneity between the trial results, the quantitative information provided by this review may only be used in an exploratory fashion. It is unlikely that FAST will ever be investigated by means of a confirmatory, large-scale RCT in the future. Thus, this Cochrane Review may be regarded as a review which provides the best available evidence for clinical practice guidelines and management recommendations. It can only be concluded from the few head-to-head studies that negative US scans are likely to reduce the incidence of MDCT scans which, given the low sensitivity of FAST (or reliability of negative results), may adversely affect the diagnostic yield of the trauma survey. At best, US has no negative impact on mortality or morbidity. Assuming that major blunt abdominal or multiple trauma is associated with 15% mortality and a CT-based diagnostic work-up is considered the current standard of care, 874, 3495, or 21,838 patients are needed per intervention group to demonstrate non-inferiority of FAST to CT-based algorithms with non-inferiority margins of 5%, 2.5%, and 1%, power of 90%, and a type-I error alpha of 5%.

In this review, the authors looked for studies that compared death rates in patients with an abdominal injury where ultrasound was used to aid diagnosis with death rates where no ultrasound was used. They also looked for evidence that ultrasound use could reduce the need to carry out other more complex and more expensive diagnostic tests. However, very few trials have been done and the authors concluded that there is insufficient evidence to justify the use of ultrasound as part of the diagnosis of patients with abdominal injury. Given this degree of uncertainty, it is probably justified to ask doctors on duty for a confirmatory CT scan in patients who have sustained an injury with a high chance of major trauma (that is, head and brain injury, cervical spine fracture, thoraco-abdominal pelvic trauma, and other injuries).

10.1002/14651858.CD004446.pub4

cochrane-simplification-train-3341

cochrane-simplification-train-3341

Twenty studies involving 1898 subjects were evaluated, including 4 studies with multiple comparisons. We found eight comparisons of TURP with contact lasers, eight with non-contact lasers, four with hybrid techniques, and one with interstitial laser coagulation (ILC). Two studies compared transurethral electrovaporization (TUVP) with contact lasers, one study compared interstitial laser coagulation with transurethral microwave thermotherapy (TUMT), and one study compared holmium contact lasers (HoLRP) with open prostatectomy. Among the studies comparing laser prostatectomy with TURP, follow-up duration ranged from 6 to 36 months. Mean age (67.2 yrs), mean baseline symptom score (20.2), and mean baseline peak urinary flow (9.2 mL/s) did not differ by treatment group. The pooled percentage improvements for mean urinary symptoms ranged from 59% to 68% with lasers and 63% to 77% with TURP. The improvements for mean peak urinary flow ranged from 56% to 119% with lasers and 96% to 127% with TURP. Overall, laser subjects were less likely to receive transfusions or develop strictures and their hospitalizations were shorter. Non-contact laser subjects were more likely to have dysuria, urinary tract infection, and retention. Re-operation occurred more often following laser procedures. Laser techniques are a useful alternative to TURP for treating BPO. Small sample sizes and differences in study design limit any definitive conclusions regarding the preferred type of laser technique. Data were insufficient to compare laser techniques with other minimally invasive procedures.

This review of 20 studies involving 1898 subjects found laser techniques to be useful and relatively safe alternatives to TURP. The small number of enrolled subjects and differences in study design limit any definitive conclusions regarding which type of laser technique is the most effective. Improvements in LUTS and urine flow slightly favored TURP, though laser procedures had fewer side effects and shorter hospitalization times. The follow-up durations of these studies ranged from 6 to 36 months and men with extremely large prostates were generally excluded from the trials. The risk of needing a reoperation for recurrent LUTS was higher following laser procedures. Study results were insufficient to adequately compare laser techniques with other minimally invasive procedures. More studies, using randomized treatment assignment, enrolling larger numbers of subjects, and comprehensive measures of treatment effectiveness and side events, are needed to better define the long-term safety and durability of laser techniques for treating LUTS associated BPO.

10.1002/14651858.CD001987.pub2

cochrane-simplification-train-3342

cochrane-simplification-train-3342

The findings of this review are based on a single trial involving 425 women with gestational diabetes. The trial compared induction of labour with expectant management (waiting for the spontaneous onset of labour in the absence of any maternal or fetal issues that may necessitate birth) in pregnant women with gestational diabetes at term. We assessed the overall risk of bias as being low for most domains, apart from performance, detection and attrition bias (for outcome perineum intact), which we assessed as being at high risk. It was an open-label trial, and women and healthcare professionals were not blinded. There were no clear differences between women randomised to induction of labour and women randomised to expectant management for maternal mortality or serious maternal morbidity (risk ratio (RR) 1.48, 95% confidence interval (CI) 0.25 to 8.76, one trial, 425 women); caesarean section (RR 1.06, 95% CI 0.64 to 1.77, one trial, 425 women); or instrumental vaginal birth (RR 0.81, 95% CI 0.45 to 1.46, one trial, 425 women). For the primary outcome of maternal mortality or serious maternal morbidity, there were no deaths in either group and serious maternal morbidity related to admissions to intensive care unit. The quality of the evidence contributing to these outcomes was assessed as very low, mainly due to the study having high risk of bias for some domains and because of the imprecision of effect estimates. In relation to primary neonatal outcomes, there were no perinatal deaths in either group. The quality of evidence for this outcome was judged as very low, mainly due to high risk of bias and imprecision of effect estimates. There were no clear differences in infant outcomes between women randomised to induction of labour and women randomised to expectant management: shoulder dystocia (RR 2.96, 95% CI 0.31 to 28.21, one trial, 425 infants, very low-quality evidence); large-for-gestational age (RR 0.53, 95% CI 0.28 to 1.02, one trial, 425 infants, low-quality evidence). There were no clear differences between women randomised to induction of labour and women randomised to expectant management for postpartum haemorrhage (RR 1.17, 95% CI 0.53 to 2.54, one trial, 425 women); admission to intensive care unit (RR 1.48, 95% CI 0.25 to 8.76, one trial, 425 women); and intact perineum (RR 1.02, 95% CI 0.73 to 1.43, one trial, 425 women). No infant experienced a birth trauma, therefore, we could not draw conclusions about the effect of the intervention on the outcomes of brachial plexus injury and bone fracture at birth. Infants of women in the induction-of-labour group had higher incidences of neonatal hyperbilirubinaemia (jaundice) when compared to infants of women in the expectant-management group (RR 2.46, 95% CI 1.11 to 5.46, one trial, 425 women). We found no data on the following prespecified outcomes of this review: postnatal depression, maternal satisfaction, length of postnatal stay (mother), acidaemia, intracranial haemorrhage, hypoxia ischaemic encephalopathy, small-for-gestational age, length of postnatal stay (baby) and cost. The authors of this trial acknowledge that it is underpowered for their primary outcome of caesarean section. The authors of the trial and of this review note that the CIs demonstrate a wide range, therefore making it inappropriate to draw definite conclusions. There is limited evidence to inform implications for practice. The available data are not of high quality and lack power to detect possible important differences in either benefit or harm. There is an urgent need for high-quality trials evaluating the effectiveness of planned birth at or near term gestation for women with gestational diabetes compared with an expectant approach.

Our search identified one trial involving 425 women and their babies. In this trial, 214 women had an induction of their labour at term, the other 211 women waited for a spontaneous onset of their labour. The findings of this trial highlighted no clear difference between the babies of women in either group in relation to the number of large babies, baby's shoulder getting stuck during birth or babies with breathing problems, low blood sugar and admission to a neonatal intensive care unit. No baby in the trial experienced birth trauma. In the group of women whose labour was induced, there were more incidences of jaundice in the babies. There was no clear difference between women in either group in relation to serious health problems for women, caesarean section, instrumental vaginal birth, postpartum haemorrhage, admission to an intensive care unit and intact perineum. There were no reports in either group of maternal deaths. It should be noted that most of the evidence was found to be of very low quality. The following outcomes were not reported: postnatal depression, maternal satisfaction, length of postnatal stay (mother), babies with high blood acid, bleeding in the baby's brain, other brain problems for the babies, babies small-for-gestational age and length of baby's postnatal stay. There is insufficient evidence to clearly identify if there are differences in health outcomes for women with gestational diabetes and their babies when elective birth is undertaken compared to waiting for labour to start spontaneously or until 41 weeks' gestation if all is well. More research is needed to answer this question.

10.1002/14651858.CD012910

cochrane-simplification-train-3343

cochrane-simplification-train-3343

We included 19 trials in this review (2286 participants: 1103 allocated to HBOT and 1153 to control). For head and neck cancer, there was an overall reduction in the risk of dying at both one year and five years after therapy (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70 to 0.98, number needed to treat for an additional beneficial outcome (NNTB) = 11 and RR 0.82, 95% CI 0.69 to 0.98, high-quality evidence), and some evidence of improved local tumour control immediately following irradiation (RR with HBOT 0.58, 95% CI 0.39 to 0.85, moderate-quality evidence due to imprecision). There was a lower incidence of local recurrence of tumour when using HBOT at both one and five years (RR at one year 0.66, 95% CI 0.56 to 0.78, high-quality evidence; RR at five years 0.77, 95% CI 0.62 to 0.95, moderate-quality evidence due to inconsistency between trials). There was also some evidence with regard to the chance of metastasis at five years (RR with HBOT 0.45 95% CI 0.09 to 2.30, single trial moderate quality evidence imprecision). No trials reported a quality of life assessment. Any benefits come at the cost of an increased risk of severe local radiation reactions with HBOT (severe radiation reaction RR 2.64, 95% CI 1.65 to 4.23, high-quality evidence). However, the available evidence failed to clearly demonstrate an increased risk of seizures from acute oxygen toxicity (RR 4.3, 95% CI 0.47 to 39.6, moderate-quality evidence). For carcinoma of the uterine cervix, there was no clear benefit in terms of mortality at either one year or five years (RR with HBOT at one year 0.88, 95% CI 0.69 to 1.11, high-quality evidence; RR at five years 0.95, 95% CI 0.80 to 1.14, moderate-quality evidence due to inconsistency between trials). Similarly, there was no clear evidence of a benefit of HBOT in the reported rate of local recurrence (RR with HBOT at one year 0.82, 95% CI 0.63 to 1.06, high-quality evidence; RR at five years 0.85, 95% CI 0.65 to 1.13, moderate-quality evidence due to inconsistency between trials). We also found no clear evidence for any effect of HBOT on the rate of development of metastases at both two years and five years (two years RR with HBOT 1.05, 95% CI 0.84 to 1.31, high quality evidence; five years RR 0.79, 95% CI 0.50 to 1.26, moderate-quality evidence due to inconsistency). There were, however, increased adverse effects with HBOT. The risk of a severe radiation injury at the time of treatment with HBOT was 2.05, 95% CI 1.22 to 3.46, high-quality evidence. No trials reported any failure of local tumour control, quality of life assessments, or the risk of seizures during treatment. With regard to the treatment of urinary bladder cancer, there was no clear evidence of a benefit in terms of mortality from HBOT at one year (RR 0.97, 95% CI 0.74 to 1.27, high-quality evidence), nor any benefit in the risk of developing metastases at two years (RR 2.0, 95% CI 0.58 to 6.91, moderate-quality evidence due to imprecision). No trial reported on failure of local control, local recurrence, quality of life, or adverse effects. When all cancer types were combined, there was evidence for an increased risk of severe radiation tissue injury during the course of radiotherapy with HBOT (RR 2.35, 95% CI 1.66 to 3.33, high-quality evidence) and of oxygen toxic seizures during treatment (RR with HBOT 6.76, 96% CI 1.16 to 39.31, moderate-quality evidence due to imprecision). We found evidence that HBOT improves local tumour control, mortality, and local tumour recurrence for cancers of the head and neck. These benefits may only occur with unusual fractionation schemes. Hyperbaric oxygenation therapy is associated with severe tissue radiation injury. Given the methodological and reporting inadequacies of the included studies, our results demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for uterine cervical or bladder cancer. There is little evidence available concerning malignancies at other anatomical sites.

We found 19 randomised trials that together included 2286 participants. The dose of oxygen per treatment session in the HBO arm was remarkably uniform, with all trials except one administering external beam radiation therapy at 3 atmospheres absolute (ATA). However, the number of treatments given ranged widely, from two sessions only, separated by three weeks, up to 40 sessions over eight weeks.The total dose of radiation was generally reduced in the HBO participants in order to reduce side effects. The follow-up period varied between trials, from six months to 10 years, although most studies followed participants for between two and five years. Adding HBO to the treatment of head and neck cancers reduced mortality at both one year and five years after therapy. Local tumour recurrence was also less likely with HBO at one year and five years in head and neck cancer. However, these advantages are achieved at the cost of some adverse effects. There was a significant increase in the rate of severe radiation tissue injury and the chance of seizures during HBO therapy. The quality of evidence was generally high with close agreement between several different trials. Similarly, there was high-quality evidence of an increased risk of having a severe reaction to the radiation while breathing HBO. The evidence for an increased risk of seizures during treatment when using HBO was of moderate quality, mainly because of the small numbers of seizures seen in the included studies. There is some evidence that breathing oxygen while at raised pressure may improve mortality and reduce tumour regrowth in cancers of the head and neck, but at the cost of increased side effects.

10.1002/14651858.CD005007.pub4

cochrane-simplification-train-3344

cochrane-simplification-train-3344

We identified four new trials for this update. In total, the evidence for this review rests on 26 trials (1369 participants). Listening to music was the main intervention used, and 23 of the studies did not include a trained music therapist. Results indicate that music interventions have a small beneficial effect on psychological distress in people with CHD and this effect is consistent across studies (MD = -1.26, 95% CI -2.30 to -0.22, P = 0.02, I² = 0%). Listening to music has a moderate effect on anxiety in people with CHD; however results were inconsistent across studies (SMD = -0.70, 95% CI -1.17 to -0.22, P = 0.004, I² = 77%). Studies that used music interventions in people with myocardial infarction found more consistent anxiety-reducing effects of music, with an average anxiety reduction of 5.87 units on a 20 to 80 point score range (95% CI -7.99 to -3.75, P < 0.00001, I² = 53%). Furthermore, studies that used patient-selected music resulted in greater anxiety-reducing effects that were consistent across studies (SMD = -0.89, 95% CI -1.42 to -0.36, P = 0.001, I² = 48%). Findings indicate that listening to music reduces heart rate (MD = -3.40, 95% CI -6.12 to -0.69, P = 0.01), respiratory rate (MD = -2.50, 95% CI -3.61 to -1.39, P < 0.00001) and systolic blood pressure (MD = -5.52 mmHg, 95% CI - 7.43 to -3.60, P < 0.00001). Studies that included two or more music sessions led to a small and consistent pain-reducing effect (SMD = -0.27, 95% CI -0.55 to -0.00, P = 0.05). The results also suggest that listening to music may improve patients' quality of sleep following a cardiac procedure or surgery (SMD = 0.91, 95% CI 0.03 to 1.79, P = 0.04). We found no strong evidence for heart rate variability and depression. Only one study considered hormone levels and quality of life as an outcome variable. A small number of studies pointed to a possible beneficial effect of music on opioid intake after cardiac procedures or surgery, but more research is needed to strengthen this evidence. This systematic review indicates that listening to music may have a beneficial effect on anxiety in persons with CHD, especially those with a myocardial infarction. Anxiety-reducing effects appear to be greatest when people are given a choice of which music to listen to. Furthermore, listening to music may have a beneficial effect on systolic blood pressure, heart rate, respiratory rate, quality of sleep and pain in persons with CHD. However, the clinical significance of these findings is unclear. Since many of the studies are at high risk of bias, these findings need to be interpreted with caution. More research is needed into the effects of music interventions offered by a trained music therapist.

For this review, we searched for additional trials on the effect of music interventions on stress and anxiety in people with coronary heart disease. We searched for studies published up until November 2012 as well as ongoing studies until November 2012. We considered all studies in which any form of participation in music (e.g. listening to music, singing, playing music) was compared with any form of standard treatment and included persons with confirmed coronary heart disease. We identified four new trials for this update. This review includes 26 trials with a total of 1369 participants. The trials were small in size. The findings suggest that listening to music may have a beneficial effect on systolic blood pressure and heart rate in people with coronary heart disease. Listening to music also appears to be effective in reducing anxiety in people with myocardial infarction, especially when they are given a choice of which music to listen to. Listening to music may also reduce pain and respiratory rate. However the size of the effects on pain and respiratory rate is small. Therefore, its clinical importance is unclear. Finally, listening to music appears to improve patients' quality of sleep following a cardiac procedure or surgery. We found no evidence of effect for depression or heart rate variability, and inconsistent results for mood. No adverse effects of music interventions were reported. The majority of the studies examined the effects of listening to pre-recorded music. More research is needed on the effects of music interventions offered by a trained music therapist. Overall, the quality of the evidence is not strong thus the results should be interpreted with caution. We did not identify any conflicts of interests in the included studies.

10.1002/14651858.CD006577.pub3

cochrane-simplification-train-3345

cochrane-simplification-train-3345

Five trials, with a total of 336 randomised participants, were included. A total of 105 participants (31%) died. Of the five included trials, four (80%) had a high risk of bias. Meta-analysis using all five trials showed that pentoxifylline reduced mortality compared with control (RR 0.64; 95% CI 0.46 to 0.89). However, this result was not supported by trial sequential analysis, which adjusts for multiple testing on accumulating data. Furthermore, four of the five trials were judged to have a high risk of bias, thus risking an overestimated intervention effect. Meta-analysis showed that pentoxifylline reduced the hepatic-related mortality due to hepatorenal syndrome (RR 0.40; 95% CI 0.22 to 0.71), but trial sequential analysis did not support this result. Data from one trial suggests that pentoxifylline may increase the occurrence of serious and non-serious adverse events compared to control. The current available data may indicate a possible positive intervention effect of pentoxifylline on all-cause mortality and mortality due to hepatorenal syndrome, and conversely, an increase in serious and non-serious adverse events. However, the evidence is not firm; no conclusions can be drawn regarding whether pentoxifylline has a positive, negative, or neutral effect on participants with alcoholic hepatitis.

We found five randomised trials, which together included 336 participants; half received pentoxifylline, and the other half received placebo or no intervention. We performed this systematic review and statistical analyses but could not show firm evidence of beneficial effects of pentoxifylline on mortality or on complications of liver diseases in patients with alcoholic hepatitis. Pentoxifylline did appear to cause more serious and non-serious side effects. In order to help decide whether pentoxifylline should be used to treat alcoholic hepatitis or not, we need well-designed, well-conducted, large randomised clinical trials, with short-term (less than one month) and long-term (more than one month) data on benefits and harms.

10.1002/14651858.CD007339.pub2

cochrane-simplification-train-3346

cochrane-simplification-train-3346

Twelve studies, with a total of 343 participants, met our inclusion criteria (four RCTs and eight before and after non-controlled studies). Of the four RCTs, one examined patients with non-epileptic seizures and three had a mixed diagnosis (pseudoseizures, conversion disorder and somatisation disorder). Most of the non-randomised studies used non-epileptic seizure patients exclusively. Overall, five studies examined the effectiveness of psychotherapy, three examined CBT, two investigated hypnosis, one assessed paradoxical intention and one had a mixed intervention design. We classified two included studies as low risk of bias, one as unclear and nine as high risk of bias. Meta-analysis could not be undertaken due to the heterogeneity of design and interventions. Most included studies reported improved outcomes for the intervention under investigation. One RCT investigating the effectiveness of CBT in this patient group found a significant reduction in seizure frequency compared to controls (P < 0.001). There is little reliable evidence to support the use of any treatment, including CBT, in the treatment of non-epileptic seizures. Further randomised controlled trials of CBT and other interventions are needed.

Non-epileptic attacks look like epileptic seizures but they are not caused by epilepsy. There have been many investigations of the causes, but evidence about successful treatment is less available. We reviewed the existing studies treating people having non-epileptic attacks. We found 12 studies looking at different types of treatment such as psychotherapy, cognitive behavioural therapy and hypnosis. Three hundred and forty three participants were recruited to these 12 studies. Four studies were randomised controlled trials, and 8 were non-randomised studies. Most of the controlled trials included patients with other diagnoses as well as non-epileptic attacks. Most of the non-randomised studies included patients with mainly non-epileptic attacks. Most included studies reported improved outcomes for the treatment they were investigating. One randomised trial investigating Cognitive Behavioural Therapy found that seizures were significantly reduced. Due to the variety of treatments and designs of the included studies, it was not possible to combine the results to produce an overall outcome for our review. Many of the studies did not use satisfactory methods which meant that the evidence was rated as high risk of bias. The overall evidence for the main outcome of reducing seizures as a result of treatment is not considered reliable except in one study. Our conclusion is there is little reliable evidence to support the use of any treatment for people with non-epileptic attacks. The evidence in this review is up to date as from 4 February 2013.

10.1002/14651858.CD006370.pub2

cochrane-simplification-train-3347

cochrane-simplification-train-3347

Sixteen studies met the inclusion criteria, all but one were from Africa, comprising two cluster randomised trials and 14 cohort studies. Antiretroviral therapy started at a hospital and maintained at a health centre (partial decentralisation) probably reduces attrition (RR 0.46, 95% CI 0.29 to 0.71, 4 studies, 39 090 patients, moderate quality evidence). There may be fewer patients lost to care with this model (RR 0.55, 95% CI 0.45 to 0.69, low quality evidence). We are uncertain whether there is a difference in attrition for antiretroviral therapy started and maintained at a health centre (full decentralisation) compared to a hospital at 12 months (RR 0.70, 95% CI 0.47 to 1.02; four studies, 56 360 patients, very low quality evidence), but there are probably fewer patients lost to care with this model (RR 0.3, 95% CI 0.17 to 0.54, moderate quality evidence). When antiretroviral maintenance therapy is delivered at home by trained volunteers, there is probably no difference in attrition at 12 months (RR 0.95, 95% CI 0.62 to 1.46, two trials, 1453 patients, moderate quality evidence). Decentralisation of HIV care aims to improve patient access and retention in care. Most data were from good quality cohort studies but confounding between site of treatment and outcomes cannot be excluded. Nevertheless, this review found that attrition appears to be lower in partial decentralisation models of treatment, where antiretrovirals were started at hospital and continued in the health centre; with antiretroviral drugs started and continued at health centres, no difference in attrition was detected, but there were fewer patients lost to care. For antiretroviral therapy provided at home by trained volunteers, no difference in outcomes were detected when compared to facility-based care.

We searched for studies up to March 2013. We found 16 studies, including two high quality randomised controlled trials and 14 studies collecting data from HIV care programmes. All but one study was conducted in Africa. The study participants included both adults and children who were followed-up for up to two years. We describe three types of care: - Partial decentralisation: starting antiretroviral therapy at the hospital, then moving to a health centre to continue treatment - Full decentralisation: starting and continuing treatment at a health centre - Providing antiretroviral therapy in the community: antiretroviral therapy is started at a health centre or hospital and thereafter provided in the community We found that if antiretroviral therapy was started at a hospital and continued in a health centre (partial decentralisation), there was probably less attrition and fewer patients were lost to care after one year (four studies, 39 090 patients). Where antiretroviral therapy was started and continued at a health centre (full decentralisation), there was probably no difference in the number of deaths and patients lost to follow-up (attrition), but overall, there were probably fewer patients lost to care after one year (four studies, 56 360 patients). If antiretroviral therapy was provided in the community, by trained volunteers, there was probably no difference detected in death or losses to care when compared to care provided at a health centre after one year (two studies, 1 453 patients). Overall, none of the models of decentralisation led to worse health outcomes. The research indicates that fewer patients are lost to care when they are continued on antiretroviral therapy at health centres rather than in hospitals. The research also did not detect a difference in the numbers of patients lost to care when they are treated in the community rather than in a health facility.

10.1002/14651858.CD009987.pub2

cochrane-simplification-train-3348

cochrane-simplification-train-3348

We included 21 trials, involving 1746 participants, in this update; six trials were new. The included trials did not report the numbers of dead and dependent participants at the end of at least three months' follow-up. Of the 12 trials that reported adverse events, five events occurred in two trials. There was no significant difference between the treatment group and the control group. We assessed 20 trials to be of a poor quality: When analysing these trials together, mailuoning was associated with a significant increase in the number of participants with an improved neurological deficit (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.23 to 0.42) and showed a significant improvement of neurological deficit with the European Stroke Scale (ESS) (mean difference (MD) (fixed) 8.29, 95% CI 3.44 to 13.15). One placebo-controlled trial, assessed to be of a better methodological quality, failed to show a significant improvement of neurological deficit at the end of three months' follow-up (MD (fixed) 2.49, 95% CI -1.45 to 6.43) or in quality of life. One trial, which reported cognitive function using the Montreal Cognitive Assessment as a continuous scale, showed a significant improvement of cognitive function (MD (fixed) 2.68, 95% CI 1.82 to 3.54). Two trials assessed activities of daily life: One trial showed a significant improvement, but the other did not. This review did not provide sufficient evidence to support the routine use of mailuoning for the treatment of people with acute ischaemic stroke. High-quality large-scale randomised controlled trials are needed to confirm the efficacy of mailuoning.

We searched for trials up to June 2014 and included 21 randomised controlled trials, involving 1746 participants, of mailuoning for people with acute ischaemic stroke. Two trials followed up participants for three months after treatment ended, but the duration of the other trials was shorter, from 14 to 38 days. A government agency funded one of the 21 included trials. We assessed 20 trials to be of a low quality. When we analysed these trials together, there was no significant difference for adverse events between the mailuoning-treatment group and the control group; mailuoning improved neurological impairment and cognitive function significantly. One trial, assessed to be of a higher quality, failed to show any significant improvement made by mailuoning on neurological deficit, activities of daily life, or quality of life. There was no convincing evidence from trials with sufficient methodological quality to support the routine use of mailuoning to promote recovery after stroke. High-quality large-scale randomised controlled trials are needed to confirm its effect. We assessed 20 of the 21 included trials to be of a poor quality for their study design; we assessed one trial to be of a higher quality, but there were fewer participants in this trial. Overall, the quality of evidence was poor.

10.1002/14651858.CD007028.pub3

cochrane-simplification-train-3349

cochrane-simplification-train-3349

Thirty-four trials were identified which included approximately 19,676 incontinent women of whom 9599 received oestrogen therapy (1464 involved in trials of local vaginal oestrogen administration). Sample sizes of the studies ranged from 16 to 16,117 women. The trials used varying combinations of type of oestrogen, dose, duration of treatment and length of follow up. Outcome data were not reported consistently and were available for only a minority of outcomes. The combined result of six trials of systemic administration (of oral systemic oestrogens) resulted in worse incontinence than on placebo (risk ratio (RR) 1.32, 95% CI 1.17 to 1.48). This result was heavily weighted by a subgroup of women from the Hendrix trial, which had large numbers of participants and a longer follow up of one year. All of the women had had a hysterectomy and the treatment used was conjugated equine oestrogen. The result for women with an intact uterus where oestrogen and progestogen were combined also showed a statistically significant worsening of incontinence (RR 1.11, 95% CI 1.04 to 1.18). There was some evidence that oestrogens used locally (for example vaginal creams or pessaries) may improve incontinence (RR 0.74, 95% CI 0.64 to 0.86). Overall, there were around one to two fewer voids in 24 hours amongst women treated with local oestrogen, and there was less frequency and urgency. No serious adverse events were reported although some women experienced vaginal spotting, breast tenderness or nausea. Women who were continent and received systemic oestrogen replacement, with or without progestogens, for reasons other than urinary incontinence were more likely to report the development of new urinary incontinence in one large study. One small trial showed that women were more likely to have an improvement in incontinence after pelvic floor muscle training (PFMT) than with local oestrogen therapy (RR 2.30, 95% CI 1.50 to 3.52). The data were too few to address questions about oestrogens compared with or in combination with other treatments, different types of oestrogen or different modes of delivery. Urinary incontinence may be improved with the use of local oestrogen treatment. However, there was little evidence from the trials on the period after oestrogen treatment had finished and no information about the long-term effects of this therapy was given. Conversely, systemic hormone replacement therapy using conjugated equine oestrogen may worsen incontinence. There were too few data to reliably address other aspects of oestrogen therapy, such as oestrogen type and dose, and no direct evidence comparing routes of administration. The risk of endometrial and breast cancer after long-term use of systemic oestrogen suggests that treatment should be for limited periods, especially in those women with an intact uterus.

The review found 34 trials including more than 19,000 women of whom over 9000 received oestrogen. The review found that significantly more women who received local (vaginal) oestrogen for incontinence reported that their symptoms improved compared to placebo. There was no evidence about whether the benefits of local oestrogen continue after stopping treatment but this seems unlikely as women would revert to having naturally low oestrogen levels. Trials investigating systemic (oral) administration, on the other hand, found that women reported worsening of their urinary symptoms. The evidence comes mainly from two very large trials including 17,642 incontinent women. These trials were investigating other effects of hormone replacement therapy as well as incontinence, such as prevention of heart attacks in women with coronary heart disease, bone fractures, breast and colorectal cancer. In addition, in one large trial women who did not have incontinence at first were more likely to develop incontinence. There may be risks from long-term use of systemic oestrogen, such as heart disease, stroke and cancer of the breast and uterus.

10.1002/14651858.CD001405.pub3

cochrane-simplification-train-3350

cochrane-simplification-train-3350

We identified and included one trial (147 women from a pre-planned sample size of 310 women) that compared the effect of prophylactic antibiotic (single-dose, second-generation cephalosporin - cefotetan or cefoxitin, 1 g intravenously) on postpartum perineal wound complications in third- or fourth-degree perineal tears compared with placebo. Perineal wound complications (wound disruption and purulent discharge) at the two-week postpartum check up were 8.20% and 24.10% in the treatment and the control groups respectively (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.12 to 0.96). However, the high failed-appointment rate may limit the generalisability of the results. The overall risk of bias was low except for incomplete outcome data. The quality of the evidence using GRADE was moderate for infection rate at two weeks' postpartum, and low for infection rate at six weeks' postpartum. Although the data suggest that prophylactic antibiotics help to prevent perineal wound complications following third- or fourth-degree perineal tear, loss to follow-up was very high. The results should be interpreted with caution as they are based on one small trial.

The review identified one trial, involving 147 women. This trial was conducted to explore the benefit of routine prophylactic antibiotics (intervention group) versus placebo (control group) for women with severe perineal tears. The result showed fewer perineal wound complications in the intervention group at two weeks postpartum. There was no statistically significant difference in perineal wound complications before discharge and at six weeks' postpartum. The one included study was terminated before it reached the pre-planned sample size and had a high rate of loss to follow-up The included study was of high methodological quality except for incomplete follow-up. We assessed reduction of perineal wound infection in third- or fourth-degree tear by antibiotic prophylaxis as low to moderate quality of the evidence. However, the results are based on one small trial and there was a high loss to follow-up. More research is needed.

10.1002/14651858.CD005125.pub4

cochrane-simplification-train-3351

cochrane-simplification-train-3351

We identified six trials eligible for inclusion, of which two are ongoing, and one awaiting classification study. The three included trials were conducted at many different sites in Europe, America, and Asia. All of the three studies recruited adult and elder participants (no children were included) with solid tumours, and compared TPO-RAs with placebo. No studies compared TPO-RAs alone, or in combination with other drugs, to no treatment, or other drugs, or another TPO-RAs. We judged the overall risk of bias as high as we found a high risk for detection bias. We assessed the risk of bias arising from inadequate blinding of outcome assessors as high for number and severity of bleeding episodes (one of the primary outcomes). To prevent CIT: We included two trials (206 participants) comparing TPO-RAs (eltrombopag, multiple-dose oral administration with chemotherapy) with placebo. The use of TPO-RAs may make little or no difference to the all-cause mortality at 33 weeks of follow-up (RR 1.35, 95% CI 0.53 to 3.45; one trial, 26 participants; low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 0.62, 95% CI 0.22 to 1.78; two trials, 206 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (RR 0.36, 95% CI 0.06 to 2.06; two trials, 206 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. To prevent recurrence of CIT: We included one trial (62 participants) comparing TPO-RAs (romiplostim, single-dose subcutaneous administration with chemotherapy) with placebo. There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 2.80, 95% CI 0.17 to 47.53; one trial, 62 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (no severe/life-threatening bleeding episodes; one trial, 62 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. We found one ongoing study (expected recruitment 74 participants), it is planned to give TPO-RAs (romiplostim, subcutaneous administration with chemotherapy) to participants, but to date this trial has not reported any outcomes. To treat CIT: We found one ongoing study (expected recruitment 83 participants), which is planned to give TPO-RAs (eltrombopag, seven days orally) to participants when their platelet counts are less than 75×109/L during chemotherapy. This trial was originally planned to complete in March 2017, however, the completion date has passed and no results are reported. The one awaiting classification study included patients without thrombocytopenia before chemotherapy (to prevent CIT), patients with thrombocytopenia during chemotherapy (to prevent recurrence of CIT), and other patients during chemotherapy (uncertain whether CIT had happened). There was no evidence for a difference in the number of patients with at least one bleeding episode of any severity (RR 0.27, 95% CI 0.07 to 1.02; one trial, 75 participants). There was no evidence for a difference in the number of patients with at least one severe/life-threatening bleeding episode (RR 0.44, 95% CI 0.03 to 6.77; one trial, 75 participants). This study did not address overall survival or quality of life. No certain conclusions can be drawn due to the lack of strong evidence in the review. The available weak evidence did not support the use of TPO-RAs for preventing CIT or preventing recurrence of CIT in patients with solid tumours. There was no evidence to support the use of TPO-RAs for treating CIT in patients with solid tumours.

We searched Cochrane Central Register of Controlled Trials, MEDLINE, online registries of ongoing trials, and conference proceedings. The evidence is current to September 2017. We found six trials eligible for inclusion, of which two are still ongoing, and one awaiting classification study. We included 268 adult and elder participants (no children were included). Two studies compared eltrombopag with placebo for patients with normal platelet counts before chemotherapy (to prevent CIT). One study compared romiplostim with placebo for patients with low platelet counts during chemotherapy (to prevent recurrence of CIT). All of the studies were funded by the drug manufacturers. To prevent CIT, the review shows that when patients (206 participants) with normal platelet count before chemotherapy are given eltrombopag (multiple-dose oral administration with chemotherapy), compared to placebo: - the use of TPO-RAs may make little or no difference to the all-cause mortality (low quality of evidence); - there is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (very low quality of evidence); - there is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (very low quality of evidence); - no studies were found that looked at overall survival, the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. To prevent recurrence of CIT, the review shows that when patients (62 participants) with low platelet counts during a chemotherapy cycle are given romiplostim (single-dose subcutaneous administration with chemotherapy), compared to placebo: - there is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (very low quality of evidence); - there is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (very low quality of evidence); - no studies were found that looked at overall survival, the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. We found one ongoing study (expected recruitment 74 participants), planning to give romiplostim (subcutaneous administration with chemotherapy) to participants. As yet, there are no reported outcomes. To treat CIT, one ongoing study (expected recruitment 83 participants) planned to give eltrombopag (seven days orally) to participants when their platelet counts are less than 75×109/L during chemotherapy. Its completion date (March 2017) has passed and no results have been reported. One study awaiting classification included patients with normal platelet counts before chemotherapy (to prevent CIT), patients with low platelet counts during chemotherapy (to prevent recurrence of CIT), and others (uncertain whether CIT had happened). There was no evidence for a difference in the number and severity of bleeding episodes. This study did not address overall survival or quality of life. There is low and very low quality evidence for the use of TPO-RAs to prevent CIT or prevent recurrence of CIT in patients with solid tumours. No certain conclusions can be drawn due to the lack of strong evidence in the review. The available weak evidence did not support the use of TPO-RAs for preventing CIT or preventing recurrence of CIT in patients with solid tumours. No completed studies looked at the use of TPO-RAs for treating CIT in patients with solid tumours.

10.1002/14651858.CD012035.pub2

cochrane-simplification-train-3352

cochrane-simplification-train-3352

We included four trials (3956 women and 3893 neonates) at a moderate risk of bias, comparing prophylactic administration of betamethasone or dexamethasone versus placebo or usual treatment without steroids in term elective caesarean section. Women randomised to treatment group received either two intramuscular doses of betamethasone in the 48 hours before delivery, or intramuscular dexamethasone (two or four doses) prior to delivery (at 37 weeks' gestation or 48 hours before delivery), and were compared to the control group who received a saline placebo or treatment as usual. Prophylactic antenatal corticosteroid administration appeared to decrease the risk of respiratory distress syndrome (RDS) (risk ratio (RR) 0.48; 95% confidence interval (CI) 0.27 to 0.87; 4 studies; 3817 participants; low-quality evidence), transient tachypnoea of the neonate (TTN) (RR 0.43; 95% CI 0.29 to 0.65; 4 studies; 3821 participants; low-quality evidence), admission to the neonatal intensive care unit (NICU) for respiratory morbidity (RR 0.42; 95% CI 0.22 to 0.79; 3 studies; 3441 participants), and admission to neonatal special care (all levels) for respiratory complications (RR 0.45; 95% CI 0.22 to 0.90; 1 study; 942 participants; low-quality evidence). Administration of antenatal corticosteroids also appeared to reduce admission to neonatal special care (RR 0.62; 95% CI 0.43 to 0.89; 2 studies; 2169 participants) and neonatal intensive care (RR 0.14; 95% CI 0.03 to 0.61; 1 study; 452 participants) for any indication, compared to placebo or usual care. Finally, prophylactic antenatal corticosteroids also appeared to reduce the length of stay in NICU by 2.70 days (mean difference (MD) -2.70; 95% CI -2.76 to -2.64; 2 studies; 32 participants). No reduction was found in the need for mechanical ventilation (RR 0.67; 95% CI 0.27 to 1.68; 3 studies; 3441 participants; very-low quality), perinatal death (RR 0.67; 95% CI 0.11 to 4.10; 4 studies; 3893 participants) or neonatal sepsis (RR 1.00; 95% CI 0.06 to 15.95; 2 studies; 2214 participants) . There were no reported events of neonatal respiratory complications (other than RDS and tachypnoea of the newborn (TTN)), chronic lung disease, duration of mechanical ventilation or maternal postpartum infection, therefore results on these outcomes are non-estimable. The studies did not provide data on other pre-defined outcomes. The quality of evidence, as assessed using GRADE was low for the outcomes of RDS, TTN and admission to NICU for respiratory morbidity, indicating that the true effect could potentially be substantially different from our estimate of effect. The results from the four trials are promising, but more high-quality studies with larger sample sizes that are adequately powered to detect the effect of prophylactic antenatal corticosteroids on outcomes of respiratory morbidity are needed, given the potential of the current studies for bias. Consideration should be given to the balance between statistical significance and clinical significance, particularly in view of the low event rates of significant respiratory morbidity (RDS or admission to NICU for respiratory complications) in this population. In addition, further trials on the long-term outcomes of these infants are needed to identify any potential harms and complications of antenatal corticosteroid administration at term.

The review identified four randomised controlled studies involving 3956 women and 3893 babies, which compared corticosteroids with usual care or placebo. Giving the mother intramuscular antenatal corticosteroids may reduce the chances of a baby needing special care for respiratory problems, and may reduce the chances of the baby being admitted to a neonatal intensive care unit. Much larger numbers of women would be needed to confirm differences in the rates of the respiratory problems themselves and any possible harms of giving the corticosteroids, for the mother and the baby. The quality of evidence from the included randomised trials was low. This means that we can not be completely confident that future trials will come to the same conclusions about the treatment benefits for the babies of mothers receiving a course of antenatal corticosteroids prior to caesarean section. Evidence suggest that there might be a beneficial effect of intramuscular corticosteroids in respiratory outcomes of the neonate in the immediate period after birth. Given that only one study has examined the long-term effects, we cannot be certain about whether there are risks and what is their magnitude. Larger randomised trials should be conducted in order to confirm the short- and long-term effects of this intervention in the general population of women undergoing elective caesarean section.

10.1002/14651858.CD006614.pub3

cochrane-simplification-train-3353

cochrane-simplification-train-3353

Sixteen studies with a combined total of 34,369 participants with an acute medical illness were included in this review. We identified 10 studies comparing heparin with placebo or no treatment and six studies comparing LMWH to UFH. Just under half of the studies had an open-label design, putting them at a risk of performance bias. Descriptions of random sequence generation and allocation concealment were missing in most of the studies. Heparin reduced the odds of deep vein thrombosis (DVT) (OR 0.41, 95% CI 0.25 to 0.67; P = 0.0004) . The estimated reductions in symptomatic non-fatal pulmonary embolism (PE) (OR 0.46; 95% CI 0.20 to 1.07; P = 0.07), fatal PE (OR 0.71; 95% CI 0.43 to 1.15; P = 0.16) and in combined non-fatal PE and fatal PE (OR 0.66, 95% CI 0.43 to 1.02; P = 0.06) associated with heparin were imprecise. Heparin resulted in an increase in major haemorrhage (OR 1.65, 95% CI 1.01 to 2.71; P = 0.05). There was no clear evidence that heparin had an effect on all-cause mortality and thrombocytopaenia. Compared with UFH, LMWH reduced the risk of DVT (OR 0.77; 95% CI 0.62 to 0.96; P = 0.02) and major bleeding (OR 0.43; 95% CI 0.22 to 0.83; P = 0.01). There was no clear evidence that the effects of LMWH and UFH differed for the PE outcomes, all-cause mortality and thrombocytopaenia. The data from this review describe a reduction in the risk of DVT in patients presenting with an acute medical illness who receive heparin thromboprophylaxis. This needs to be balanced against an increase in the risk of bleeding associated with thromboprophylaxis. The analysis favoured LMWH compared with UFH, with a reduced risk of both DVT and bleeding.

This review of 16 trials in 34,369 non-surgical patients who suffered an acute medical illness found that heparin reduced the number of patients suffering DVTs but also increased the risk of bleeding complications when compared to participants that received a placebo or no medication. We had some concerns over how reliable the results were from the unblinded studies, which made up just under half of the studies. Also, most of the studies were lacking explanations of how the allocation of the treatments was performed. The lower risk of PEs (when combining those that caused death and those that did not) with heparin could have been a chance effect. There was no clear evidence of a difference in the rate of death or thrombocytopaenia. The review also found that patients who were given LMWH developed fewer DVTs and fewer bleeding complications compared with those given UFH, leading to the conclusion that LMWH is more effective and carries a lower risk of adverse events in preventing blood clots than with UFH. There was no clear evidence of differences between LMWH and UFH for PE, death or thrombocytopaenia.

10.1002/14651858.CD003747.pub4

cochrane-simplification-train-3354

cochrane-simplification-train-3354

We screened 926 individual references and identified three studies that satisfied the inclusion criteria. Fifty-nine participants (37 men and 22 women) aged between 54 and 78 years were randomised initially, 47 participants completed the treatment. One study had a parallel design and two had a cross-over design. The studies included people with a variety of cancers and also differed in the dosage, route of administration, frequency and duration of treatment. One trial, which compared ghrelin with placebo, found that ghrelin improved food intake (very low-quality evidence) and had no adverse events (very low-quality evidence). Due to unavailability of data we were unable to report on comparisons for ghrelin versus no treatment or alternative experimental treatment modalities, or ghrelin in combination with other treatments or ghrelin analogues/ghrelin mimetics/ghrelin potentiators. Two studies compared a higher dose of ghrelin with a lower dose of ghrelin, however due to differences in study designs and great diversity in the treatment provided we did not pool the results. In both trials, food intake did not differ between participants on higher-dose and lower-dose ghrelin. None of the included studies assessed data on body weight. One study reported higher adverse events with a higher dose as compared to a lower dose of ghrelin. All studies were at high risk of attrition bias and bias for size of the study. Risk of bias in other domains was unclear or low. We rated the overall quality of the evidence for primary outcomes (food intake, body weight, adverse events) as very low. We downgraded the quality of the evidence due to lack of data, high or unclear risk of bias of the studies and small study size. There is insufficient evidence to be able to support or refute the use of ghrelin in people with cancer cachexia. Adequately powered randomised controlled trials focusing on evaluation of safety and efficacy of ghrelin in people with cancer cachexia is warranted.

We found three studies that recruited a total of 59 cancer patients (37 men and 22 women) aged between 54 and 78 years. Forty-seven cancer patients completed the treatment. Studies differed in study design and included people with a variety of cancers. Studies also differed in dosage, route of injection, frequency and duration of treatment. One study compared ghrelin with a placebo while two studies compared different doses of ghrelin (higher dose with lower dose). Outcomes of interest to cancer patients with loss of appetite and weight loss, such as improvement in food intake and improvement in body weight, were not adequately reported. All three included studies were funded by government agencies. One study received an additional grant from a pharmaceutical company. We found insufficient evidence that using ghrelin demonstrated differences in food intake. We found no evidence that using ghrelin alone or in combination made any difference to body weight. We could not reach any conclusions about its side effects. The limited amount of information means that we could not draw any conclusions. We rated the quality of evidence from studies using four levels: high, moderate, low, or very low. High-quality evidence means that we are very confident in the results. Very low-quality evidence means that we are very uncertain about the results. The evidence in this review was of very low quality.

10.1002/14651858.CD012229.pub2

cochrane-simplification-train-3355

cochrane-simplification-train-3355

The search identified eight trials including 500 participants. Six trials were conducted in the USA and two in Europe. 1. Parenteral nutrition (PN) versus oral nutrition: based on one study with 157 participants, PN may increase postoperative complications within 30 days (risk ratio (RR) 1.40, 95% confidence interval (CI) 1.07 to 1.82; low-quality evidence). We downgraded the quality of evidence for serious study limitations (unclear risk of selection, performance and selective reporting bias) and serious imprecision. This corresponds to 198 more complications per 1000 participants (95% CI 35 more to 405 more). Length of hospital stay may be similar (mean difference (MD) 0.5 days higher, CI not reported; low-quality evidence). 2. Immuno-enhancing nutrition versus standard nutrition: based on one study including 29 participants, immuno-enhancing nutrition may reduce 90-day postoperative complications (RR 0.31, 95% CI 0.08 to 1.23; low-quality evidence). These findings correspond to 322 fewer complications per 1000 participants (95% CI 429 fewer to 107 more). Length of hospital stay may be similar (MD 0.20 days, 95% CI 1.69 lower to 2.09 higher; low-quality evidence). We downgraded the quality of evidence of both outcomes for very serious imprecision. 3. Preoperative oral nutritional support versus normal diet: based on one study including 28 participants, we are very uncertain if preoperative oral supplements reduces postoperative complications. We downgraded quality for serious study limitations (unclear risk of selection, performance, attrition and selective reporting bias) and very serious imprecision. The study did not report on length of hospital stay. 4. Early postoperative feeding versus standard postoperative management: based on one study with 102 participants, early postoperative feeding may increase postoperative complications (very low-quality evidence) but we are very uncertain of this finding. We downgraded the quality of evidence for serious study limitations (unclear risk of selection and performance bias) and very serious imprecision. Length of hospital stay may be similar (MD 0.95 days less, CI not reported; low-quality evidence). We downgraded the quality of evidence for serious study limitations (unclear risk of selection and performance bias) and serious imprecision. 5. Amino acid with dextrose versus dextrose: based on two studies with 104 participants, we are very uncertain whether amino acids reduce postoperative complications (very low-quality evidence). We are also very uncertain whether length of hospital stay is similar (very low-quality evidence). We downgraded the quality of evidence for both outcomes for serious study limitations (unclear and high risk of selection bias; unclear risk of performance, detection and selective reporting bias), serious indirectness related to the patient population and very serious imprecision. 6. Branch chain amino acids versus dextrose only: based on one study including 19 participants, we are very uncertain whether complication rates are similar (very low-quality evidence). We downgraded the quality of evidence for serious study limitations (unclear risk of selection, performance, detection, attrition and selective reporting bias), serious indirectness related to the patient population and very serious imprecision. The study did not report on length of hospital stay. 7. Perioperative oral nutritional supplements versus oral multivitamin and mineral supplement: based on one study with 61 participants, oral supplements compared to a multivitamin and mineral supplement may slightly decrease postoperative complications (low-quality evidence). These findings correspond to 135 fewer occurrences per 1000 participants (95% CI 256 fewer to 65 more). Length of hospital stay may be similar (low-quality evidence). We downgraded the quality of evidence of both outcomes for study limitations and imprecision. Based on few, small and dated studies, with serious methodological limitations, we found limited evidence for a benefit of perioperative nutrition interventions. We rated the quality of evidence as low or very low, which underscores the urgent need for high-quality research studies to better inform nutritional support interventions for people undergoing surgery for bladder cancer.

The evidence is current up to 22 February 2019. There were eight studies conducted including 500 people in hospital. There were seven different ways in which nutrition was given. 1. Feeding into a vein versus oral nutrition: based on one study that included 157 people, we found that feeding into a vein may increase complications after surgery. However, there may be little or no difference in length of hospital stay. 2. Immuno‐enhancing nutrition versus standard supplements: immuno‐enhancing nutrition has high levels of nutrients that are thought to improve the immune function and was given in one study that included 29 people. We found that this form of nutrition may decrease complications 90 days after surgery, but may have little effect on length of hospital stay. 3. Preoperative oral nutrition support versus diet: based on one study that included 28 people, we are uncertain if oral supplements before surgery improve complications after surgery. Length of hospital stay was not reported. 4. Early postoperative feeding versus standard care: based on one study that included 102 people, early postoperative feeding may increase postoperative complications after surgery, but we are very uncertain of this finding. Length of hospital stay may be similar. 5. Amino acids versus dextrose: amino acids are the building blocks of proteins and dextrose is sugary water. From two studies that included 104 people, we are uncertain whether complications may be reduced. Length of hospital stay may be similar. 6. Branch chain versus dextrose: branch chain are a type of amino acid. From one study that included 19 people, we are very uncertain whether complication rates are similar. Length of hospital stay was not reported. 7. Perioperative oral nutritional supplements versus multivitamin and mineral supplement: from one study that included 61 people, oral supplements compared to a multivitamin and mineral supplement may slightly decrease postoperative complications. Length of hospital stay may be similar. The certainty of the evidence for all outcomes in this review was low or very low, meaning that the true effect may be very different or is likely very different from what we found.

10.1002/14651858.CD010127.pub2

cochrane-simplification-train-3356

cochrane-simplification-train-3356

Fourteen trials with 2647 participants met the inclusion criteria. The interventions included in this review report on agonistic pharmacological interventions (buprenorphine, methadone and naltrexone) compared to no intervention, other non-pharmacological treatments (e.g. counselling) and other pharmacological drugs. The methodological trial quality was poorly described, and most studies were rated as 'unclear' by the reviewers. The biggest threats to risk of bias were generated through blinding (performance and detection bias) and incomplete outcome data (attrition bias). Studies could not be combined all together because the comparisons were too different. Only subgroup analysis for type of pharmacological treatment were done. When compared to non-pharmacological, we found low quality evidence that agonist treatments are not effective in reducing drug use or criminal activity, objective results (biological) (two studies, 237 participants (RR 0.72 (95% CI 0.51 to 1.00); subjective (self-report), (three studies, 317 participants (RR 0.61 95% CI 0.31 to 1.18); self-report drug use (three studies, 510 participants (SMD: -0.62 (95% CI -0.85 to -0.39). We found low quality of evidence that antagonist treatment was not effective in reducing drug use (one study, 63 participants (RR 0.69, 95% CI 0.28 to 1.70) but we found moderate quality of evidence that they significantly reduced criminal activity (two studies, 114 participants, (RR 0.40, 95% CI 0.21 to 0.74). Findings on the effects of individual pharmacological interventions on drug use and criminal activity showed mixed results. In the comparison of methadone to buprenorphine, diamorphine and naltrexone, no significant differences were displayed for either treatment for self report dichotomous drug use (two studies, 370 participants (RR 1.04, 95% CI 0.69 to 1.55), continuous measures of drug use (one study, 81 participants, (mean difference (MD) 0.70, 95% CI -5.33 to 6.73); or criminal activity (one study, 116 participants, (RR 1.25, 95% CI 0.83 to 1.88) between methadone and buprenorphine. Similar results were found for comparisons with diamorphine with no significant differences between the drugs for self report dichotomous drug use for arrest (one study, 825 participants, (RR 1.25, 95% CI 1.03 to 1.51) or naltrexone for dichotomous measures of reincarceration (one study, 44 participants, (RR 1.10, 95% CI 0.37 to 3.26), and continuous outcome measure of crime, (MD -0.50, 95% CI -8.04 to 7.04) or self report drug use (MD 4.60, 95% CI -3.54 to 12.74). When compared to non-pharmacological treatment, agonist treatments did not seem effective in reducing drug use or criminal activity. Antagonist treatments were not effective in reducing drug use but significantly reduced criminal activity. When comparing the drugs to one another we found no significant differences between the drug comparisons (methadone versus buprenorphine, diamorphine and naltrexone) on any of the outcome measures. Caution should be taken when interpreting these findings, as the conclusions are based on a small number of trials, and generalisation of these study findings should be limited mainly to male adult offenders. Additionally, many studies were rated at high risk of bias.

The review authors searched scientific databases and Internet resources to identify randomised controlled trials (where participants are allocated at random to one of two or more treatment groups) of interventions to reduce, eliminate, or prevent relapse of drug use or criminal activity of drug-using offenders. We included males and female of any age or ethnicity. We identified 14 trials of pharmacological interventions for drug-using offenders. The interventions included: (1) naltrexone in comparison with routine parole, social psychological treatment or both; (2) methadone maintenance in comparison with different counselling options; and (3) naltrexone, diamorphine and buprenorphine in comparison with a non-pharmacological alternative and in combination with another pharmacological treatment. Studies could not be combined all together because the comparisons were too different. When compared to non-pharmacological, we found low quality evidence that agonist treatments are not effective in reducing drug use or criminal activity . We found low quality of evidence that antagonist treatment was not effective in reducing drug use but we found moderate quality of evidence that they significantly reduced criminal activity. When comparing the drugs to one another we found no significant differences between the drug comparisons (methadone versus buprenorphine, diamorphine and naltrexone) on any of the outcome measures suggesting that one pharmacological drug does not preside over another. One study provided some cost comparisons between buprenorphine and methadone, but data were not sufficient to generate a cost-effectiveness analysis. In conclusion, we found that pharmacological interventions do reduce subsequent drug use and criminal activity (to a lesser extent). Additionally, we found individual differences and variation between the degree to which successful interventions were implemented and were able to sustain reduction of drug use and criminal activity. This review was limited by the lack of information reported in this group of trials and the quality of the evidence was low. The evidence is current to May 2014.

10.1002/14651858.CD010862.pub2

cochrane-simplification-train-3357

cochrane-simplification-train-3357

Of 23 eligible trials identified, 22 had been completed and 17 provided results for relevant outcomes. Completed trials comparing interventions for problem drinking to no intervention reported reduced motor-vehicle crashes and related injuries, falls, suicide attempts, domestic violence, assaults and child abuse, alcohol-related injuries and injury emergency visits, hospitalizations and deaths. Reductions ranged from 27% to 65%. Because few trials were sufficiently large to assess effects on injuries, individual effect estimates were generally imprecise. We did not combine the results quantitatively because the interventions, patient populations, and outcomes were so diverse. The most commonly evaluated intervention was brief counseling in the clinical setting. This was studied in seven trials, in which injury-related deaths were reduced: relative risk (RR) 0.65; 95% confidence interval (CI) 0.21 to 2.00. However, this reduction may have been due to chance. The majority of trials of brief counseling also showed beneficial effects on diverse non-fatal injury outcomes. Interventions for problem drinking appear to reduce injuries and their antecedents (e.g. falls, motor vehicle crashes, suicide attempts). Because injuries account for much of the morbidity and mortality from problem drinking, larger studies are warranted to evaluate the effect of treating problem drinking on injuries.

The reviewers found 17 studies of programs that reported whether working with problem drinkers reduced injuries. Several different approaches were evaluated, the most common being brief counseling by health workers. The evidence from these studies suggests that action with problem drinkers is effective in reducing both injuries and events that lead to injury (such as falls, motor vehicle crashes, and suicide attempts). However, more research is needed to calculate the level of effectiveness accurately and to determine which type of program works best.

10.1002/14651858.CD001857.pub2

cochrane-simplification-train-3358

cochrane-simplification-train-3358

Twelve papers reporting on 10 studies met the inclusion criteria. These studies dealt with the following: working wrist splints (5), resting hand and wrist splints (2), special shoes and insoles (3). There is evidence that wearing wrist splints during work statistically significantly decreases grip strength and does not affect pain, morning stiffness, pinch grip, or quality of life after up to six months of regular wear. We found no evidence that resting wrist and hand splints change pain, grip strength, Ritchie Index, or number of swollen joints. However, participants who wore these splints for two months reported that they preferred use to non-use, and padded resting splints to unpadded ones. The one study of special shoes provided evidence of significant benefits of wearing extra-depth shoes for two months, including less pain on walking and stair climbing, and more minutes of pain free walking time. Extra-depth shoes with semi-rigid insoles provided better pain relief than extra-depth shoes alone when worn over 12 weeks. Supporting insoles prevented progression of hallux valgus angle but did not affect pain or function. There is insufficient evidence to make firm conclusions about the effectiveness of working wrist splints in decreasing pain or increasing function for people with RA. Potential adverse effects, such as decreased range of motion, do not seem to be an issue although some of these splints decrease grip strength and dexterity. Similarly, preliminary evidence suggests that resting hand and wrist splints do not seem to affect range of motion (ROM) or pain, although participants preferred wearing a resting splint to not wearing one. There is evidence that extra-depth shoes and molded insoles decrease pain during weight-bearing activities such as standing, walking, and stair-climbing. Supported insoles may be effective in preventing progression of hallux abductus angle but do not appear to have any impact on pain.

Ten studies examined the effects of working wrist splints, resting hand and wrist splints, and wearing special shoes/ insoles in people with rheumatoid arthritis. Although there is no evidence that wearing resting wrist and hand splints changed pain, grip strength, or number of swollen joints, participants who wore these splints for two months preferred to wear them, and also preferred padded splints. One study provided evidence that wearing extra-depth shoes for two months resulted in significant benefits of less pain on walking and stair climbing. Extra-depth shoes with semi-rigid insoles provided better pain relief than extra-depth shoes alone.

10.1002/14651858.CD004018

cochrane-simplification-train-3359

cochrane-simplification-train-3359

We included 31 trials (8019 participants) in the analysis. In short-term (≤ 6 weeks) trials, pimecrolimus cream was significantly more effective and well-tolerated than vehicle (cream base, but not containing pimecrolimus). In long-term trials (≥ 6 months), pimecrolimus was significantly better than vehicle in preventing flares (9 trials, 3091 participants, RR 1.47, 95% CI 1.32 to 1.64 at six months) and in improving quality of life. Pimecrolimus was significantly less effective than two topical corticosteroids, i.e. 0.1% triamcinolone acetonide for investigators' global assessment (1 trial, 658 participants, RR 0.75, 95% CI 0.67 to 0.83) and 0.1% betamethasone valerate for participants' global assessment (1 trial, 87 participants, RR 0.61, 95% CI 0.45 to 0.81) at three weeks. Pimecrolimus was also associated with significantly more overall withdrawals and skin burning. None of the trials reported on key adverse effects such as thinning of skin. Pimecrolimus was significantly less effective than 0.1% tacrolimus for investigators' global assessment at 6 weeks (RR 0.58, 95% CI 0.46 to 0.74) and led to more withdrawals due to lack of efficacy (RR 2.37, 95% CI 1.10 to 5.08) based on 2 trials involving 639 participants, but there was no significant difference in proportions of participants experiencing any adverse events. Topical pimecrolimus is less effective than moderate and potent corticosteroids and 0.1% tacrolimus. The therapeutic role of topical pimecrolimus is uncertain due to the absence of key comparisons with mild corticosteroids.

This review included data from 31 clinical trials involving 8019 participants. In the short-term (less than six weeks) treatment of eczema, we found pimecrolimus was more effective and well-tolerated when compared against vehicle (cream base not containing any pimecrolimus). Likewise, pimecrolimus was better than vehicle cream in preventing deterioration in eczema based on data from 9 trials involving 3091 participants. However, we found that 3 weeks treatment with pimecrolimus was less effective than a moderate (triamcinolone acetonide, data from 1 trial with 658 participants) and a potent topical corticosteroid (betamethasone valerate, data from 1 trial with 87 participants). Furthermore, 6-weeks treatment with pimecrolimus was less effective and caused more participants to drop out of treatment due to lack of efficacy than tacrolimus based on 2 trials involving 639 participants. Pimecrolimus caused a similar rate of adverse events to vehicle cream but had a lower overall dropout rate. In contrast, pimecrolimus had higher dropout rates and caused more skin burning than topical corticosteroids. None of the trials reported on key adverse effects, such as thinning of skin. Pimecrolimus caused a similar rate of adverse events to tacrolimus. There were no cancer-related events reported in any of the 31 clinical trials. This review did not find evidence to support the notion that pimecrolimus was better than moderate or potent corticosteroids or tacrolimus in treating eczema. However, there is a distinct lack of trials comparing pimecrolimus against mild-potency corticosteroids.

10.1002/14651858.CD005500.pub2

cochrane-simplification-train-3360

cochrane-simplification-train-3360

This review included 28 studies. The updated analysis included 6871 randomised women, while the original review had 3643 women. Of the 28 included studies, we considered 19 studies to be at low risk of bias overall; however, some studies failed to report details on allocation concealment and methods of outcome assessment for those outcomes that are more likely to be influenced by a lack of blinding (for example tumour response rate). Studies varied in the taxane-containing chemotherapy backbone, and the comparator arms and were categorised into three groups: Regimen A plus taxane versus Regimen A (2 studies); Regimen A plus taxane versus Regimen B (14 studies); and single-agent taxane versus Regimen C (13 studies). Thirteen studies used paclitaxel, 14 studies used docetaxel, and 1 study allowed the investigator to decide on the type of taxane; the majority of studies delivered a taxane every 3 weeks. Twenty studies administered taxanes as first-line treatment, and 21 studies involved anthracycline naïve women in the metastatic setting. The combined HR for overall survival and time to progression favoured the taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.88 to 0.99, P = 0.002, deaths = 4477; and HR 0.92, 95% CI 0.87 to 0.97, P = 0.002, estimated 5122 events, respectively) with moderate to substantial heterogeneity across trials. If the analyses were restricted to studies of first-line chemotherapy, this effect persisted for overall survival (HR 0.93, 95% CI 0.87 to 0.99, P = 0.03) but not for time to progression (HR 0.96, 95% CI 0.90 to 1.02, P = 0.22). Tumour response rates appeared to be better with taxane-containing chemotherapy in assessable women (RR 1.20, 95% CI 1.14 to 1.27, P < 0.00001) with substantial heterogeneity across studies. Taxanes were associated with an increased risk of neurotoxicity (RR 4.84, 95% CI 3.18 to 7.35, P < 0.00001, 24 studies) and hair loss (RR 2.37, 95% CI 1.45 to 3.87, P = 0.0006, 11 studies) but less nausea/vomiting compared to non-taxane-containing regimens (RR 0.62, 95% CI 0.46 to 0.83, P = 0.001, 26 studies). Leukopaenia and treatment-related death did not differ between the two groups (RR 1.07, 95% CI 0.97 to 1.17, P = 0.16, 28 studies; and RR 1.00, 95% CI 0.63 to 1.57, P = 0.99, 23 studies, respectively). For quality of life measures, none of the individual studies reported a difference in overall or any of quality of life subscales between taxane-containing and non-taxane chemotherapy regimens. Taxane-containing regimens appear to improve overall survival, time to progression, and tumour response rate in women with metastatic breast cancer. Taxanes are also associated with an increased risk of neurotoxicity but less nausea and vomiting compared to non-taxane-containing regimens. The considerable heterogeneity encountered across studies probably reflects the varying efficacy of the comparator regimens used in these studies and indicates that taxane-containing regimens are more effective than some, but not all, non-taxane-containing regimens.

The evidence is current to February 2013. We included 28 studies that randomised 6871 women. Women were assigned to receive either a taxane-containing chemotherapy regimen (single taxane or in combination with other chemotherapy drugs) or a non-taxane chemotherapy regimen. There were variations in the taxane-containing chemotherapy regimen and the non-taxane treatments. Approximately half of the studies used paclitaxel and the other half used docetaxel, and in the majority of cases, taxanes were administered every three weeks. Of the 28 studies, 20 studies included women who received taxanes as their first treatment after their diagnosis of metastatic breast cancer, and 21 studies involved women who had not been previously treated with anthracyclines in the metastatic setting. From those studies reporting median follow-up, this ranged from 9 months to 69 months. This review showed that chemotherapy regimens including taxanes improved survival and decreased the progression of metastatic breast cancer. If the analyses were restricted to those studies where women received taxanes as their first treatment after their diagnosis of metastatic breast cancer, the survival benefit persisted. Taxanes also appeared to cause tumours to shrink more than chemotherapy regimens without taxanes. However, there were differences in side effects. The risk of experiencing neurotoxicity (tingling of hands and feet) with taxanes increased compared to non-taxane chemotherapy. Hair loss also seemed to be more likely with taxane than with non-taxane-containing regimens. However, less nausea/vomiting was observed with taxanes. There was no difference in the rates of leukopaenia (low white blood cells) or treatment-related deaths between taxane and non-taxane chemotherapy. Of the studies that reported quality of life measures, there did not appear to be any differences (overall or on subscales) in quality of life between the two groups. We considered 19 out of the 28 studies to be at low risk of bias overall. However, some studies failed to report details on concealing drug treatments and methods of outcome assessment for those outcomes more likely to be at risk of bias (for example tumour response rate). The degree of variability seen across the included studies probably reflects the varying efficacy of the non-taxane chemotherapy regimens used in these studies and indicates that taxane-containing chemotherapies are more effective than some, but not all, non-taxane-containing regimens.

10.1002/14651858.CD003366.pub3

cochrane-simplification-train-3361

cochrane-simplification-train-3361

We included 32 studies (21 RCTs and 11 CBAs); 26 of these (16 RCTs and 10 CBAs) were in meta-analyses. More than 50% of the RCTs were judged to have low risk of bias for random selection and incomplete outcome assessment. We judged most RCTS to be unclear for allocation concealment, blinding of outcome assessment, and selective outcome reporting. Because children and parents knew that they were given food, we judged blinding of participants and personnel to be at high risk for all studies. Growth. Supplementary feeding had positive effects on growth in low- and middle-income countries. Meta-analysis of the RCTs showed that supplemented children gained an average of 0.12 kg more than controls over six months (95% confidence interval (CI) 0.05 to 0.18, 9 trials, 1057 participants, moderate quality evidence). In the CBAs, the effect was similar; 0.24 kg over a year (95% CI 0.09 to 0.39, 1784 participants, very low quality evidence). In high-income countries, one RCT found no difference in weight, but in a CBA with 116 Aboriginal children in Australia, the effect on weight was 0.95 kg (95% CI 0.58 to 1.33). For height, meta-analysis of nine RCTs revealed that supplemented children grew an average of 0.27 cm more over six months than those who were not supplemented (95% CI 0.07 to 0.48, 1463 participants, moderate quality evidence). Meta-analysis of seven CBAs showed no evidence of an effect (mean difference (MD) 0.52 cm, 95% CI -0.07 to 1.10, 7 trials, 1782 participants, very low quality evidence). Meta-analyses of the RCTs demonstrated benefits for weight-for-age z-scores (WAZ) (MD 0.15, 95% CI 0.05 to 0.24, 8 trials, 1565 participants, moderate quality evidence), and height-for-age z-scores (HAZ) (MD 0.15, 95% CI 0.06 to 0.24, 9 trials, 4638 participants, moderate quality evidence), but not for weight-for-height z-scores MD 0.10 (95% CI -0.02 to 0.22, 7 trials, 4176 participants, moderate quality evidence). Meta-analyses of the CBAs showed no effects on WAZ, HAZ, or WHZ (very low quality evidence). We found moderate positive effects for haemoglobin (SMD 0.49, 95% CI 0.07 to 0.91, 5 trials, 300 participants) in a meta-analysis of the RCTs. Psychosocial outcomes. Eight RCTs in low- and middle-income countries assessed psychosocial outcomes. Our meta-analysis of two studies showed moderate positive effects of feeding on psychomotor development (SMD 0.41, 95% CI 0.10 to 0.72, 178 participants). The evidence of effects on cognitive development was sparse and mixed. We found evidence of substantial leakage. When feeding was given at home, children benefited from only 36% of the energy in the supplement. However, when the supplementary food was given in day cares or feeding centres, there was less leakage; children took in 85% of the energy provided in the supplement. Supplementary food was generally more effective for younger children (less than two years of age) and for those who were poorer/ less well-nourished. Results for sex were equivocal. Our results also suggested that feeding programmes which were given in day-care/feeding centres and those which provided a moderate-to-high proportion of the recommended daily intake (% RDI) for energy were more effective. Feeding programmes for young children in low- and middle-income countries can work, but good implementation is key.

We included 32 studies; 21 randomised controlled trials (in which children were randomly assigned to receive either supplementary feeding (intervention group) or not (a control group), and 11 controlled before-and-after studies (in which outcomes were observed before and after treatment in a group of children who were not randomly assigned to an intervention and a control group). The number of children in them ranged from 30 to 3166. Most studies were from low- and middle-income countries; three were from high-income countries. We found that, in low- and middle-income countries, providing additional food to children aged three months to five years led to small gains in weight (0.24 kg a year in both RCTs and CBAs) and height (0.54 cm a year in RCTs only; no evidence of an effect in other study designs),and moderate increases in haemoglobin. We also found positive impacts on psychomotor development (skills that involve mental and muscular activity). We found mixed evidence on effects of supplementary feeding on mental development. In high-income countries, two studies found no benefits for growth. The one effective study involved Aboriginal children. We found that food was often redistributed ('leakage') within the family; when feeding was home-delivered, children benefited from only 36% of the energy given in the supplement. However, when the supplementary food was given in day care centres or feeding centres, there was much less leakage; children took in 85% of the energy provided in the supplement. When we looked at different groups supplementary food was more effective for younger children (under two years old) and for those who were poorer or less well-nourished. Results for sex were mixed. Feeding programmes that were well-supervised and those that provided a greater proportion of required daily food for energy were generally more effective. We judged evidence from the RCTs to be of moderate quality and evidence from the CBAs to be of low quality.

10.1002/14651858.CD009924.pub2

cochrane-simplification-train-3362

cochrane-simplification-train-3362

Thirty-two trials (2281 participants) met our inclusion criteria. Most trials (25) included participants with rotator cuff disease and calcific deposits, five trials included participants with rotator cuff disease and no calcific deposits, and two trials included a mixed population of participants with and without calcific deposits. Twelve trials compared shock wave therapy to placebo, 11 trials compared high-dose shock wave therapy (0.2 mJ/mm² to 0.4 mJ/mm² and above) to low-dose shock wave therapy. Single trials compared shock wave therapy to ultrasound-guided glucocorticoid needling, ultrasound-guided hyaluronic acid injection, transcutaneous electric nerve stimulation (TENS), no treatment or exercise; dual session shock wave therapy to single session therapy; and different delivery methods of shock wave therapy. Our main comparison was shock wave therapy versus placebo and results are reported for the 3 month follow up. All trials were susceptible to bias; including selection (74%), performance (62%), detection (62%), and selective reporting (45%) biases. No trial measured participant-reported pain relief of 30%. However, in one trial (74 participants), at 3 months follow up, 14/34 participants reported pain relief of 50% or greater with shock wave therapy compared with 15/40 with placebo (risk ratio (RR) 1.10, 95% confidence interval (CI) 0.62 to 1.94); low-quality evidence (downgraded for bias and imprecision). Mean pain (0 to 10 scale, higher scores indicate more pain) was 3.02 points in the placebo group and 0.78 points better (0.17 better to 1.4 better; clinically important change was 1.5 points) with shock wave therapy (9 trials, 608 participants), moderate-quality evidence (downgraded for bias). Mean function (scale 0 to 100, higher scores indicate better function) was 66 points with placebo and 7.9 points better (1.6 better to 14 better, clinically important difference 10 points) with shock wave therapy (9 trials, 612 participants), moderate-quality evidence (downgraded for bias). Participant-reported success was reported by 58/150 people in shock wave therapy group compared with 35/137 people in placebo group (RR 1.59, 95% CI 0.87 to 2.91; 6 trials, 287 participants), low-quality evidence (downgraded for bias and imprecision). None of the trials measured quality of life. Withdrawal rate or adverse event rates may not differ between extracorporeal shock wave therapy and placebo, but we are uncertain due to the small number of events. There were 11/34 withdrawals in the extracorporeal shock wave therapy group compared with 13/40 withdrawals in the placebo group (RR 0.75, 95% CI 0.43 to 1.31; 7 trials, 581 participants) low-quality evidence (downgraded for bias and imprecision); and 41/156 adverse events with extracorporeal shock wave therapy compared with 10/139 adverse events in the placebo group (RR 3.61, 95% CI 2.00 to 6.52; 5 trials, 295 participants) low-quality evidence (downgraded for bias and imprecision). Subgroup analyses indicated that there were no between-group differences in pain and function outcomes in participants who did or did not have calcific deposits in the rotator cuff. Based upon the currently available low- to moderate-certainty evidence, there were very few clinically important benefits of shock wave therapy, and uncertainty regarding its safety. Wide clinical diversity and varying treatment protocols means that we do not know whether or not some trials tested subtherapeutic doses, possibly underestimating any potential benefits. Further trials of extracorporeal shock wave therapy for rotator cuff disease should be based upon a strong rationale and consideration of whether or not they would alter the conclusions of this review. A standard dose and treatment protocol should be decided upon before further research is conducted. Development of a core set of outcomes for trials of rotator cuff disease and other shoulder disorders would also facilitate our ability to synthesise the evidence.

We included 32 trials (2281 participants), published up to November 2019. Twelve trials compared shock wave therapy to placebo. Eleven trials compared high- and low-dose shock wave therapy, although dosages varied across trials. Single trials compared shock wave therapy to other treatments including ultrasound-guided glucocorticoid needling, transcutaneous electric nerve stimulation (TENS), exercise, or no treatment; or different regimens of shock wave therapy. Overall, 61% of participants were women, the average age was 52 years, and the average duration of the condition was 33 months. Two trials were funded by manufacturers of shock wave machines. Participant-reported pain relief of 50% or greater (one trial): • four more people out of 100 reported pain relief of 50% or more (ranging from 19 fewer to 26 more). 42 out of 100 people reported pain relief of 50% or greater with shock wave therapy compared with 38 out of 100 with placebo. Pain (higher scores mean more pain) (nine trials): • Improved pain by 8% (ranging from 2% better to 14% better) or 0.78 points better (ranging from 0.17 better to 1.4 better) on a 0- to 10-point scale. People who had shock wave therapy rated their pain as 2.2 points and people who had placebo rated their pain as 3 points. Function (ability to use the shoulder; higher scores meanbetter function) (nine trials): • Improved by 8% (ranging from 1.6% to 14%) or 8 points better (ranging from 1.6 better to 14 better) on a 0- to 100-point scale. People who had shock wave therapy rated their function as 74 points and people who had placebo rated their function as 66 points. Participant-reported success (six trials): • 15% (ranging from 3% fewer to 49% more) more people reported their treatment a success. 41 out of 100 people reported treatment success with shock wave therapy and 26 out of 100 people reported treatment success with placebo. Withdrawals due to side effects (seven trials): • 3% fewer (ranging from 6% fewer to 3% more) people withdrew from treatment due to side effects. 8 out of 100 people withdrew from treatment with shock wave therapy and 10 out of 100 people withdrew from the placebo group. Side effects (five trials): • 19% more people reported side effects (ranging from 7% more to 40% more): 26 out of 100 people had a side effect with shock wave therapy and seven out of 100 people had a side effect with placebo. In people with rotator cuff disease, moderate-certainty evidence (downgraded due to bias) shows that shock wave therapy probably does not improve pain and function compared with placebo, and low-certainty evidence (downgraded due to bias and lack of accuracy) shows there may be no improvement in those with a pain reduction of 50% or more and participant-reported success. We are uncertain if withdrawals or side effects differed between groups due to small number of events. It did not appear to matter if participants had calcific deposits or not. We are uncertain if higher doses of shock wave therapy have benefits with more side effects compared with lower doses, as there was only low- or very low-certainty evidence available, and we cannot recommend a particular treatment dose. Side effects included treatment-related pain, bruising and bleeding although these were generally minor and short-lived. Rare and serious side effects, including loss of blood supply and bone death, while possible, were not reported.

10.1002/14651858.CD008962.pub2

cochrane-simplification-train-3363

cochrane-simplification-train-3363

One study was included involving 39 participants who received either enzyme replacement therapy with galsulfase (recombinant human arylsulphatase B) or placebo. This small study was considered to be of overall unclear quality, since the authors did not report how both the allocation generation and concealment were performed. The key finding at 24 weeks in the 12-minute walk test was a statistically significant mean difference of 92.00 meters between the two groups in favour of the galsulfase group (95% confidence interval 11.00 to 172.00). While week 24 results for the three-minute stair climb demonstrated some improvement in the treatment group as compared to the placebo group, this was not significant, mean difference 5.70 (95% confidence interval -0.10 to 11.50). A significant decrease in the urinary glycosaminoglycan levels was observed in favour of the galsulfase group at 24 weeks, mean difference -227.00 (95% confidence interval -264.00 to -190.00). In general, the dose of galsulfase was well tolerated and there were no significant differences in relation to adverse events. These events include drug-related adverse events, serious and severe adverse events, those during infusion, drug-related adverse events during infusion, and deaths. More infusion-related reactions were observed in the galsulfase group and were managed with interruption or slowing of infusion rate or administration of antihistamines or corticosteroids drugs. No deaths occurred during the study. The results of one small study (based on 24-week randomised phase of the study and prior to the open-label extension) demonstrated that galsulfase is more effective than placebo in people with MPS VI, with significant improvements in the 12-minute walk test and a reduction in urinary glycosaminoglycans. There were no significant changes in cardiac or pulmonary functions, liver or spleen volume, overnight apnea-hypopnea, height and weight, quality of life and adverse effects. Further studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy with galsulfase.

The review includes one study with 39 people with mucopolysaccharidosis type VI aged between five and 20 years old. The study compared galsulfase to placebo (a substance which contains no medication) and people were selected for one treatment or the other randomly. The study lasted for 24 weeks (with an open-label extension period of an additional 24 weeks). Given that there is only one small study included, the evidence for this treatment is limited. The included study showed that motor function improved in people who had received galsulfase, especially in their ability to walk. There was also an improvement in the results of urine tests, which showed lower levels of the chemicals associated with MPS VI (glycosaminoglycan levels). These results were seen in a short study and may reflect only short-term effects. There were no significant differences between treatment with galsulfase and placebo in relation to adverse effects. More research is required to study the long-term effects on heart and lung function, quality of life and survival. The methods of the study design were not clearly described and the impact of this on possible bias is unclear.

10.1002/14651858.CD009806.pub2

cochrane-simplification-train-3364

cochrane-simplification-train-3364

Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility-sparing surgery and conventional surgery. Recurrence-free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low-quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single-arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options.

Five retrospective studies (including 535 women with a diagnosis of GCT) met our inclusion criteria. Two studies, which attempted to identify factors associated with better outcomes (in terms of overall survival), suggested that no apparent evidence could be found of differences in overall survival between surgical approaches (including whether the surgery was keyhole or open) whether a patient underwent lymphadenectomy (removal of lymph nodes) or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all women combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent only surgery. In three studies, no apparent evidence to suggest that disease recurrence was associated with type of adjuvant chemotherapy or type of surgery, although surgical staging may be important. In one study, disease recurrence was not noted to be different between patients who underwent fertility-sparing surgery, where only the affected fallopian tube and ovary were removed, and those treated with conventional surgery, in which both tubes and ovaries were removed. Given the high overall survival rate, fertility-sparing surgery may be an important treatment option for young patients wishing to have children in the future. Recurrence-free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life. All studies were at very high risk of bias (low quality). All five studies were retrospective (looked at past findings) and were at very high risk of bias (low quality); therefore future studies should look at current evidence in randomised studies on adult GCT of the ovary. Three randomised studies comparing chemotherapy are ongoing. The study that may be able to answer the question regarding best choice of chemotherapy in sex cord stromal tumours is an ongoing randomised study comparing the efficacy of two drugs (carboplatin and paclitaxel) versus standard chemotherapy (BEP - bleomycin, etoposide, cisplatin). Overall, the evidence in this review is of low quality, which may seriously weaken confidence in the results. Further research is very likely to have an important impact on evidence provided in the future. The effectiveness and safety of different ways of treating patients with adult-onset granulosa cell tumour of the ovary have not yet been assessed by high-quality studies. Such trials are required to assess toxicity and quality of life associated with different treatments and to assess the safety of the types of surgery used. Generally, current evidence is not robust enough to allow recommendations for changes in clinical practice.

10.1002/14651858.CD006912.pub2

cochrane-simplification-train-3365

cochrane-simplification-train-3365

We included seven randomised trials with 296 participants. Four trials examined nifedipine and the remainder nicardipine. Comparisons were with placebo in six trials and with both dazoxiben and placebo in one trial (only the nifedipine versus placebo data were used within this review). Treatment with oral calcium channel blockers was minimally effective in primary Raynaud's phenomenon at decreasing the frequency of attacks (standardised mean difference of 0.23; 95% confidence interval (CI) 0.08 to 0.38, P = 0.003). This translates to 1.72 (95% CI 0.60 to 2.84) fewer attacks per week on calcium channel blockers compared to placebo. One trial provided details on duration of attacks reporting no statistically significant difference between the nicardipine and placebo groups (no P value reported). Only two trials provided any detail of statistical comparisons of (unvalidated) severity scores between treatment groups: one of these trials (60 participants) reported a mean severity score of 1.55 on placebo and 1.36 on nicardipine, difference 0.2 (95% CI of difference 0 to 0.4, no P value reported) and the other trial (three participants only with primary Raynaud's phenomenon) reported a median severity score of 2 on both nicardipine and placebo treatment (P > 0.999) suggesting little effect on severity. Participant-preference scores were included in four trials, but in only two were results specific to participants with primary Raynaud's phenomenon, and scoring systems differed between trials: scores differed between treatments in only one trial, in which 33% of participants on placebo and 73% on nifedipine reported improvement in symptoms (P < 0.001). Physiological measurements were included as outcome measures in five trials (different methodologies were used in each): none of these trials found any statistically significant between-treatment group differences. Treatment with calcium channel blockers appeared to be associated with a number of adverse reactions, including headaches, flushing and oedema (swelling). Overall, the trials were classed as being at low or unclear risk of bias; and the quality of the evidence presented was moderate for number of attacks, very low for duration of attacks, high for severity scores and low for patient preference scores. The randomised controlled trials included in this review provide moderate quality evidence that oral calcium channel blockers are minimally effective in the treatment of primary Raynaud's phenomenon as measured by the frequency of attacks and high-quality evidence that they have little effect on severity. We are unable to comment on duration of attacks or on patient preference due to the very low and low quality of evidence as a result of small sample sizes in the included studies and the variable data quality of outcome measures.

This review examined seven randomised trials which included 296 participants. Although overall all the trials were classed as being at low or unclear risk of bias, the sample size of the included trials was small and there was unclear reporting of outcomes. Two different calcium channel blockers were included: nifedipine and nicardipine. Comparisons in six trials were with placebo and in one trial with both placebo and another type of drug (although only data relating to the calcium channel blocker and placebo were used in this case). Treatment with oral calcium channel blockers was found to be minimally effective in primary Raynaud's phenomenon, reducing the frequency of attacks by around 1.7 attacks per person per week. One trial provided information on duration of attacks reporting no difference between the calcium channel blocker and placebo groups . Oral calcium channel blockers had no effect on severity scores in the two trials in which these were assessed. Only two trials reported preference scores (whereby participants are asked which treatment they prefer) specifically in those with primary Raynaud's phenomenon, and in only one of these was there a between-treatment group difference (participants preferred nifedipine to placebo). Physiological measurements (for example measurement of finger blood flow) were performed in five trials, data could not be combined as the methods were too different, no differences found between calcium channel blocker and placebo treatment were seen in any trial. Treatment with calcium channel blockers was associated with a number of adverse events including headaches, flushing and ankle swelling. Quality of the evidence The results of this review were limited by the low number of participants recruited to the studies and by the limitations of currently used outcome measures. This review shows moderate quality evidence that oral calcium channel blockers are minimally effective in the treatment of primary Raynaud's phenomenon, as measured by the frequency of attacks, and high quality evidence that they have little effect on severity. We are unable to comment on duration of attacks and patient preference due to the very low and low quality of evidence provided by the trials in relation to these outcomes.

10.1002/14651858.CD002069.pub5

cochrane-simplification-train-3366

cochrane-simplification-train-3366

Six studies met the inclusion criteria, with a total of 334 adult participants. We identified no studies that included children as participants. All studies were affected by high risk of bias due to a lack of blinding of participants and personnel; five studies were affected by high risk of bias for lack of blinding of outcome assessors. There was high or unclear risk of biases affecting some studies across all the Cochrane risk of bias measures. Three studies compared a psychological intervention (either cognitive behaviour therapy or mindfulness-based cognitive therapy) with a control intervention. Data regarding depression symptom outcome measures were combined in a meta-analysis, but did not find an effect in favour of treatment (SMD -0.14; 95% CI -0.47 to 0.19; Z = 0.83; P = 0.41). The other comparisons comprised of single studies of depression symptoms and compared; cognitive behaviour therapy versus supportive psychotherapy (SMD -0.09; 95% CI -0.65 to 0.48; Z = 0.30; P = 0.77); repetitive transcranial magnetic stimulation plus tricyclic antidepressant (rTMS + TCA) versus tricyclic antidepressant alone (SMD -0.84; 95% CI -1.36 to -0.32; Z = 3;19, P = 0.001); and a supervised exercise program versus exercise as usual (SMD -0.43; 95% CI -0.88 to 0.03; Z = 1.84; P = 0.07). There was very-low quality evidence, small effect sizes and wide variability of results, suggesting that no comparisons showed a reliable effect for any intervention. Only one study mentioned minor, transient adverse events from repetitive transcranial magnetic stimulation. The review did not find compelling evidence in favour of any intervention. Future studies should focus on participants with a diagnosed TBI and include only participants who have a diagnosis of depression, or who record scores above a clinical cutoff on a depression measure. There is a need for additional RCTs that include a comparison between an intervention and a control that replicates the effect of the attention given to participants during an active treatment.

We found six studies, with a total of 334 adult participants. We found no studies that included people younger than 18 years of age. Four studies investigated psychological interventions. One study investigated an exercise intervention, and another investigated repetitive transcranial magnetic stimulation (rTMS). Three studies compared a psychological therapy (cognitive behaviour therapy or mindfulness-based cognitive therapy) with a no-treatment control intervention. When the data for these studies were combined, there was no reliable effect in support of psychological therapy. One study compared cognitive behavioural therapy with another psychological intervention (supportive psychotherapy), and did not find an effect in favour of either intervention. One study compared a supervised exercise programme with exercise as usual, but did not find a effect in favour of either intervention. One study compared rTMS plus an antidepressant medication with the antidepressant medication alone. Because the quality of the evidence was very low, it was not possible to draw the conclusion that the addition of rTMS improved outcomes. Only one study, of rTMS, reported any harmful effects and these were relatively minor and resolved quickly. The quality of the evidence was rated very low. All studies were at high risk of bias in some ways, and therefore it was not possible to draw conclusions in support of any intervention. There was a high degree of variability in the main results, which meant we could have little confidence in the findings. Some studies had major methodological flaws. It is not possible to recommend any particular treatment based on the current evidence. The review authors have made some recommendations to improve the quality of the evidence in future studies.

10.1002/14651858.CD009871.pub2

cochrane-simplification-train-3367

cochrane-simplification-train-3367

Two trials were included this review. One (involving 213 women and 213 neonates) evaluated the impact of Hib vaccination during pregnancy and the other study (involving 2116 women and 2049 neonates) evaluated the impact of viral influenza vaccination during pregnancy. Overall, the HiB vaccination trial was judged to be at 'high risk of bias' due to inadequate randomisation while the other trial was judged to be at 'low risk of bias'. Hib vaccination during pregnancy versus placebo One trial involving 213 women and 213 neonates evaluating the impact of Hib vaccination during pregnancy was included under this comparison. The study did not report on any of this review's prespecified primary outcomes (including mortality, respiratory tract infection and sepsis) or secondary outcomes (including adverse events) except preterm delivery. There was no clear difference between the Hib vaccination and placebo control groups in terms of preterm delivery (risk ratio (RR) 1.28, 95% confidence interval (CI) 0.12 to 13.86, one study, 213 participants), fetal distress (RR 1.23, 95% CI 0.67 to 2.26, one study, 213 infants), intubation (RR 1.03, 95% CI 0.55 to 1.95, one study, 213 infants) and neonatal jaundice (RR 1.01, 95% CI 0.52 to 1.97, one study, 213 infants). We could not grade the evidence for quality due to lack of outcome data. Viral influenza vaccination during pregnancy versus placebo One trial involving 2116 women and 2049 infants evaluating the impact of trivalent inactivated influenza vaccine (IIV3) during pregnancy was included under this comparison. There was no clear difference between the viral influenza and placebo control group in terms of most of this review's primary outcomes: maternal death (RR 4.96, 95% CI 0.24 to 103.24, moderate quality evidence), infant death up to 175 days after birth (RR 0.71, 95% CI 0.37 to 1.37, moderate quality evidence), perinatal death (stillbirth and death in the first week of life) (RR 1.32, 95% CI 0.73 to 2.38, moderate quality evidence), influenza-like illness in women (RR 0.96, 95% CI 0.79 to 1.16) or their babies (RR 1.02, 95% CI 0.94 to 1.09), any respiratory illness in women (RR 0.97, 95% CI 0.91 to 1.04, high quality evidence) or their babies (RR 1.01, 95% CI 0.95 to 1.07, high quality evidence). There were also no clear differences between vaccination and placebo control groups in terms of maternal hospitalisation for any infection (RR 2.27, 95% CI 0.94 to 5.49; 2116 women, moderate quality evidence), and neonatal hospitalisation for sepsis (RR 1.60, 95% CI 0.73 to 3.50; 2049 infants, moderate quality evidence). However, viral influenza vaccination during pregnancy was associated with a reduction in reverse-transcriptase–polymerase-chain-reaction (RT-PCR) confirmed influenza among infants (RR 0.51, 95% CI 0.30 to 0.88, one study, 2049 infants) and women (RR 0.50, 95% CI 0.29 to 0.86, one study, 2116 women). In terms of this review's secondary outcomes, there were no clear differences in terms of the impact on pregnancy outcomes (miscarriage, preterm labour and stillbirth), hospitalisation for respiratory infection among women and infants. Similarly, there was no difference between the viral influenza vaccine and placebo control groups in terms of any adverse systemic reactions. There is limited evidence (from one small trial at a high risk of bias) on the effectiveness on Hib during pregnancy for improving maternal, neonatal and infant health outcomes. Evidence from one large high quality trial on the effectiveness of viral influenza vaccine during pregnancy suggests reduced RT-PCR confirmed influenza among women and their babies, suggesting the potential of this strategy for scale up but further evidence from varying contexts is required. Further trials for both Hib and viral influenza vaccines with appropriate study designs and suitable comparison groups are required. There are currently two 'ongoing' studies - these will be incorporated into the review in future updates.

Two trials were included this review. One trial (considered to be at a high risk of bias) evaluated the impact of Hib vaccination during pregnancy and the other trial (judged to be at a low risk of bias) evaluated the impact of viral influenza vaccination during pregnancy. In one small study (involving 213 women, mainly Hispanic and with low income, and 213 neonates, conducted in the US), women were given either Hib vaccination or a placebo control at between 34 to 36 weeks gestation. This trial did not report on any of this review's primary outcomes, including: mortality, respiratory tract infection or sepsis among the women or their babies. Nor did the study report on any of this review's other secondary outcomes apart from preterm birth and there were no clear differences between the vaccination and placebo groups. In one large trial (involving 2116 women and 2049 infants, conducted in Soweto, South Africa) pregnant women received either inactivated viral influenza vaccination or a placebo control. Viral influenza vaccination was associated with a reduction in confirmed influenza among women and their babies. However, there was no clear difference between groups in terms of pregnancy outcomes (miscarriage, preterm labour and stillbirth), influenza-like illness in women or their babies (high quality evidence), any respiratory illness, hospitalisation for respiratory infections and deaths among women (moderate quality evidence) and their babies (moderate quality evidence), neonatal hospitalisation for sepsis (moderate quality evidence), or maternal hospitalisation for any infection (moderate quality evidence). Similarly, there was no clear difference in any adverse systemic reactions between the vaccine and placebo groups. Evidence from one large high quality trial on the effectiveness of viral influenza vaccine during pregnancy suggests reduced reverse-transcriptase–polymerase-chain-reaction (RT-PCR) ) confirmed influenza among women and their babies, suggesting the potential of this strategy for scale up but further evidence from varying contexts is required. Further trials for both Hib and viral influenza vaccines with appropriate study designs and suitable comparison groups are required. There are currently two ongoing studies - these will be incorporated into this review in future updates.

10.1002/14651858.CD009982.pub2

cochrane-simplification-train-3368

cochrane-simplification-train-3368

Only one study was eligible. Chowdhry (1984) enrolled 23 infants < 1250 g and 25 - 28 weeks gestation with transient hypothyroxinaemia (serum total T4 ≤ 4 μg/dl and TSH ≤ 20 IU/L). Infants were randomised to thyroxine 10 μg/kg/day or placebo beginning on day 15 and continuing daily for seven weeks. Chowdhry (1984) reported no neonatal mortality and one infant death in each group prior to discharge. No significant difference was reported in CLD at 28 days or 36 weeks, patent ductus arteriosus, necrotising enterocolitis, retinopathy or prematurity, weight gain, growth in head circumference or length. No significant difference was reported for mean T4 levels between thyroxine and placebo treated infants on day 21, 35, 49, 63 and 77 after birth. Free T4 was not measured. Neurodevelopmental follow up was inadequate to draw any conclusions from. There is insufficient evidence to determine whether use of thyroid hormones for treatment of preterm infants with transient hypothyroxinaemia results in changes in neonatal morbidity and mortality, or reductions in neurodevelopmental impairments. Further research is required.

A systematic overview of randomised trials does not provide sufficient evidence to determine whether thyroid hormone treatment of preterm infants with transiently low thyroid hormone levels results in changes in neonatal outcomes or reductions in developmental impairments. Extremely premature infants frequently have transiently low thyroid hormone levels in the first weeks after birth. These low thyroid hormone levels are associated with an increased incidence of complications and death in the newborn period and longer term developmental impairments. Thyroid hormone therapy might prevent these problems. One small trial comparing thyroid hormone treatment to no treatment of infants with transiently low thyroid hormone levels reported no benefit from treatment of these infants. However, this is insufficient evidence to determine if thyroid hormone treatment is effective. Further research is needed.

10.1002/14651858.CD005945.pub2

cochrane-simplification-train-3369

cochrane-simplification-train-3369

A total of 1299 references were identified by the searches. After removal of duplicates, 794 references were left. Out of these, two abstract reports of one ongoing randomised trial fulfilled the inclusion criteria of the review. This ongoing trial studies total withdrawal of immunosuppression in patients who receive a calcineurin inhibitor (cyclosporine or tacrolimus) or mycophenolate mofetil as the only immunosuppressive agent. The trial compares withdrawal of calcineurin inhibitor or mycophenolate mofetil with continuation of calcineurin inhibitor or mycophenolate mofetil. However, no trial results on the outcomes of interest to this review were available. This review shows that strategies regarding calcineurin inhibitor minimisation, that is, reduction or withdrawal, without substitution versus continuation of calcineurin inhibitor treatment lack evidence from randomised trials. More research with calcineurin inhibitor reduction and withdrawal regimens is needed to optimise dosing and timing of calcineurin inhibitor treatment in order to achieve optimal patient and graft survival with a minimum of adverse events. Specifically regarding calcineurin inhibitor reduction versus no reduction, we recommend that randomised trials evaluating calcineurin inhibitor reduction versus continuation of calcineurin inhibitor treatment are conducted. Regarding calcineurin inhibitor withdrawal, we recommend that mechanisms for tolerance and 'graft acceptance' are clarified, and patient groups likely to tolerate calcineurin inhibitor withdrawal are identified in order to select the right patients for total withdrawal of calcineurin inhibitors without substitution with another immunosuppressive drug. The randomised trials should only be performed in highly selected patients.

The aim of the review was to compare reduction or withdrawal of tacrolimus or cyclosporine without substitution with another immunosuppressive agent with continuation of tacrolimus or cyclosporine. Through systematic searches of medical databases we found one ongoing randomised clinical trial investigating total withdrawal of immunosuppressive drugs but, at the time of conducting this review, no trial results on the outcome measures of interest to this review were published. Thus, we cannot reach any conclusion on beneficial or harmful effects of calcineurin inhibitor minimisation for liver transplant recipient patients.

10.1002/14651858.CD008852.pub2

cochrane-simplification-train-3370

cochrane-simplification-train-3370

We included18 RCTs (n = 1321 patients). Seven trials were published as full-text papers, and 11 trials only as meeting abstracts. All the included trials had adequate methods of randomization and allocation concealment. The results suggest that, compared with placebo or neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular blockade regardless of the depth of the block. We identified 2, 4, and 16 mg/kg of sugammadex for reversal of rocuronium-induced neuromuscular blockade at T2 reappearance , 1 to 2 post-tetanic counts, and 3 to 5 minutes after rocuronium, respectively. The number of trials are very limited regarding vecuronium and pancuronium. Serious adverse events occurred in < 1% of all patients who received the medication. There was no significant difference between sugammadex and placebo in terms of the prevalence of drug-related adverse events (RR 1.20, 95% CI 0.61 to 2.37; P = 0.59, I2 = 0%, 5 RCTs). Also, no significant difference was found between sugammadex and neostigmine for adverse events (RR 0.98, 95% CI 0.48 to1.98; P = 0.95, I2 = 43%, 3 RCTs). Sugammadex was shown to be effective in reversing rocuronium-induced neuromuscular blockade. This review has found no evidence of a difference in the instance of unwanted effects between sugammadex, placebo or neostigmine. These results need to be confirmed by future trials on larger patient populations and with more focus on patient-related outcomes.

In this review article we have included 18 trials on the efficacy and safety of sugammadex. The trials included a total of 1321 patients. Sugammadex was shown to be more effective than placebo (no medication) or neostigmine in reversing muscle relaxation caused by neuromuscular blockade during surgery and is relatively safe. Serious complications occurred in less than 1% of the patients who received sugammadex. The results of this review article (specially the safety results) need to be confirmed by future trials on larger patient populations.

10.1002/14651858.CD007362.pub2

cochrane-simplification-train-3371

cochrane-simplification-train-3371

We included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias. All studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis. Abstinence at end of treatment was no more likely with Δ9-tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence). There was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported. Adverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence). There was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence). There was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence). Available evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness. There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.

We identified 21 randomised controlled trials (clinical studies where people are allocated at random to one of two or more treatment groups) involving 909 participants treated with active medicines, and 846 who received placebo (a pretend treatment). Key features of dependent drug use are compulsive use, loss of control over use and withdrawal symptoms on cessation of drug use. This review included studies where participants were described as dependent or were likely to be dependent based on cannabis use occurring several days a week, or daily. The mean age of participants in individual studies ranged from 22 to 41 years, excluding three studies that targeted young people. Most (75%) study participants were male. Most (16) of the studies were undertaken in the USA, with three occurring in Australia, one in Canada and one in Israel. The studies tested a wide range of medicines to reduce the symptoms of cannabis withdrawal and to promote cessation or reduction of cannabis use. Four studies received study medicines from the manufacturing pharmaceutical company but none were funded by pharmaceutical companies. One study did not report funding or medicine source. For the outcome of abstinence at the end of treatment, Δ9-tetrahydrocannabinol (THC, the major constituent in cannabis) preparations were probably ineffective; antidepressants called selective serotonin reuptake inhibitors, mixed action antidepressants, a medicine called buspirone and a medicine called N-acetylcysteine may also have been ineffective; and we are uncertain about the effect of anticonvulsants and mood stabilisers. For the outcome of completion of the scheduled period of treatment, THC preparations, mixed action antidepressants, anticonvulsants and mood stabilisers may not have been effective, we were uncertain about the effect of SSRI antidepressants, and N-acetylcysteine probably did not support treatment completion. The use of anticonvulsants and mood stabilisers may have increased the likelihood that people left treatment early. THC preparations and N-acetylcysteine were probably no more likely to cause side effects than placebo, mixed action antidepressants and buspirone may have been no more likely to cause side effects than placebo, and we were uncertain about SSRI antidepressants. Based on current research, all medicines should be considered still experimental. The quality of the evidence for many of the outcomes in this review was low or very low because each medicine was investigated by a small number of studies (ranging from one to four), each study involved small numbers of participants, there was some inconsistency in the findings and there was a risk of bias due to study participants dropping out of treatment.

10.1002/14651858.CD008940.pub3

cochrane-simplification-train-3372

cochrane-simplification-train-3372

We identified 11 studies (1172 participants). We assessed seven out of 11 studies as having high overall risk of bias. There was low-quality evidence that MID was associated with worse leg pain than MD/OD at follow-up ranging from six months to two years (e.g. at one year: MD 0.13, 95% CI 0.09 to 0.16), but differences were small (less than 0.5 points on a 0 to 10 scale) and did not meet standard thresholds for clinically meaningful differences. There was low-quality evidence that MID was associated with worse LBP than MD/OD at six-month follow-up (MD 0.35, 95% CI 0.19 to 0.51) and at two years (MD 0.54, 95% CI 0.29 to 0.79). There was no significant difference at one year (0 to 10 scale: MD 0.19, 95% CI -0.22 to 0.59). Statistical heterogeneity was small to high (I2 statistic = 35% at six months, 90% at one year and 65% at two years). There were no clear differences between MID techniques and MD/OD on other primary outcomes related to functional disability (Oswestry Disability Index greater than six months postoperatively) and persistence of motor and sensory neurological deficits, though evidence on neurological deficits was limited by the small numbers of participants in the trials with neurological deficits at baseline. There was just one study for each of the sciatica-specific outcomes including the Sciatica Bothersomeness Index and the Sciatica Frequency Index, which did not need further analysis. For secondary outcomes, MID was associated with lower risk of surgical site and other infections, but higher risk of re-hospitalisation due to recurrent disc herniation. In addition, MID was associated with slightly lower quality of life (less than 5 points on a 100-point scale) on some measures of quality of life, such as some physical subclasses of the 36-item Short Form. Some trials found MID to be associated with shorter duration of hospitalisation than MD/OD, but results were inconsistent. MID may be inferior in terms of relief of leg pain, LBP and re-hospitalisation; however, differences in pain relief appeared to be small and may not be clinically important. Potential advantages of MID are lower risk of surgical site and other infections. MID may be associated with shorter hospital stay but the evidence was inconsistent. Given these potential advantages, more research is needed to define appropriate indications for MID as an alternative to standard MD/OD.

We found 11 studies up to November 2013, examining 1172 people, with studies ranging from 22 to 325 participants, and people aged from 12 to 70 years. All had tried non-surgical treatments and all had leg pain that was worse than their back pain. The follow-up period after surgery ranged from five days to 56 months. People who had a MD/OD had less pain in their legs, and less low back pain, but the difference was small. They were less likely to need a second operation because the first had been unsuccessful. They felt slightly better in some physical aspects of their quality of life, but again the difference was too small to be meaningful. In terms of complications, the two operations were similar, though people who had a MD/OD were more likely to have wound infections. Many of the studies were carried out on a small number of people and had a high risk of bias, so the overall quality of the evidence for leg and low back pain was low.

10.1002/14651858.CD010328.pub2

cochrane-simplification-train-3373

cochrane-simplification-train-3373

Fifteen studies (2,223,592 participants - 25,008 treated and 2,198,584 untreated) that fulfilled the inclusion criteria for this review were identified from the literature search. The meta-analysis demonstrated that treatment for CIN did not adversely affect the chances of conception. The overall pregnancy rate was higher for treated (43%) versus untreated women (38%; RR 1.29, 95% CI 1.02 to 1.64; 4 studies, 38,050 participants, very low quality), although the inter-study heterogeneity was considerable (P < 0.01). The pregnancy rates in treated and untreated women with an intention to conceive (88% versus 95%, RR 0.93, 95% CI 0.80 to 1.08; 2 studies, 70 participants, very low quality) and the number of women requiring more than 12 months to conceive (14% versus 9%, RR 1.45, 95% CI 0.89 to 2.37; 3 studies, 1348 participants, very low quality) were no different. Although the total miscarriage rate (4.6% versus 2.8%, RR 1.04, 95% CI 0.90 to 1.21; 10 studies, 39,504 participants, low quality) and first trimester miscarriage rate (9.8% versus 8.4%, RR 1.16, 95% CI 0.80 to 1.69, 4 studies, 1103 participants, low quality) was similar for treated and untreated women, CIN treatment was associated with an increased risk of second trimester miscarriage, (1.6% versus 0.4%, RR 2.60, 95% CI 1.45 to 4.67; 8 studies, 2,182,268 participants, low quality). The number of ectopic pregnancies (1.6% versus 0.8%, RR 1.89, 95% CI 1.50 to 2.39; 6 studies, 38,193 participants, low quality) and terminations (12.2% versus 7.4%, RR 1.71, 95% CI 1.31 to 2.22; 7 studies, 38,208 participants, low quality) were also higher in treated women. The results should be interpreted with caution. The included studies were often small with heterogenous design. Most of these studies were retrospective and of low or very low quality (GRADE assessment) and were therefore prone to bias. Subgroup analyses for the individual treatment methods and comparison groups and analysis to stratify for the cone length was not possible. This meta-analysis suggests that treatment for CIN does not adversely affect fertility, although treatment was associated with an increased risk of miscarriage in the second trimester. These results should be interpreted with caution as the included studies were non-randomised and many were of low or very low quality and therefore at high risk of bias. Research should explore mechanisms that may explain the increase in mid-trimester miscarriage risk and stratify this impact of treatment by the length of the cone and the treatment method used.

We included all studies that assessed fertility and early pregnancy outcomes in women who had local treatment of CIN versus untreated women. We identified fifteen suitable studies.Fertility outcomesThe results suggest that local treatment of the cervix does not adversely affect the ability to conceive; in fact the overall pregnancy rate was higher for treated women when compared to untreated women (43% versus 38%). There was no difference in the pregnancy rates in women that intended to conceive (88% treated versus 95% untreated) or in the number of women requiring more than 12 months to conceive (15% treated versus 9% untreated). Early pregnancy outcomes The rates of total (less than 24 weeks of gestation) and first trimester (less than 12 weeks of gestation) miscarriage were no different. However, women after treatment had a significantly higher second trimester miscarriage rate (between 12 and 24 weeks of gestation) compared to untreated controls (1.6% versus 0.4%). The rates of ectopic pregnancies and terminations of pregnancy were higher for treated versus untreated women. The results should be interpreted with caution as the included studies were small and of mixed design. Most of the studies were of low quality and retrospective (looking at information recorded previously). Investigation of the effect of different treatments techniques and of the size of the tissue removed (i.e. cone length) was not possible. The results suggest that treatment for CIN does not adversely affect the chances of a successful conception, although treatment is associated with an increased risk of miscarriage in the second trimester. These conclusions should be interpreted with caution as the quality of the included studies was low or very low. Future research should investigate the impact related to the extent of the treatment and the treatment method used.

10.1002/14651858.CD008478.pub2

cochrane-simplification-train-3374

cochrane-simplification-train-3374

We included 25 studies involving 10,996 women. Study methods were not well described in many of the included studies and thus assessing risk of bias was difficult. The main limitations of the studies were lack of blinding and high attrition. Studies were mainly funded by international organisations, universities, and ministries of health within the countries. Approximately one third of the included studies did not provide a funding source. Although quality across studies was variable, the results consistently showed that intermittent iron supplementation (alone or with any other vitamins and minerals) compared with no intervention or a placebo, reduced the risk of having anaemia (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.49 to 0.87; 11 studies, 3135 participants; low-quality evidence), and improved the concentration of haemoglobin (mean difference (MD) 5.19 g/L, 95% CI 3.07 to 7.32; 15 studies, 2886 participants; moderate-quality evidence), and ferritin (MD 7.46 μg/L, 95% CI 5.02 to 9.90; 7 studies, 1067 participants; low-quality evidence). Intermittent regimens may also reduce the risk of having iron deficiency (RR 0.50, 95% CI 0.24 to 1.04; 3 studies, 624 participants; low-quality evidence), but evidence was inconclusive regarding iron deficiency anaemia (RR 0.07, 95% CI 0.00 to 1.16; 1 study, 97 participants; very low-quality evidence) and all-cause morbidity (RR 1.12, 95% CI 0.82 to 1.52; 1 study, 119 participants; very low-quality evidence). Women in the control group were less likely to have any adverse side effects than those receiving intermittent iron supplements (RR 1.98, 95% CI 0.31 to 12.72; 3 studies, 630 participants; moderate-quality evidence). In comparison with daily supplementation, results showed that intermittent supplementation (alone or with any other vitamins and minerals) produced similar effects to daily supplementation (alone or with any other vitamins and minerals) on anaemia (RR 1.09, 95% CI 0.93 to 1.29; 8 studies, 1749 participants; moderate-quality evidence). Intermittent supplementation may produce similar haemoglobin concentrations (MD 0.43 g/L, 95% CI −1.44 to 2.31; 10 studies, 2127 participants; low-quality evidence) but lower ferritin concentrations on average (MD −6.07 μg/L, 95% CI −10.66 to −1.48; 4 studies, 988 participants; low-quality evidence) compared to daily supplementation. Compared to daily regimens, intermittent regimens may also reduce the risk of having iron deficiency (RR 4.30, 95% CI 0.56 to 33.20; 1 study, 198 participants; very low-quality evidence). Women receiving iron supplements intermittently were less likely to have any adverse side effects than those receiving iron supplements daily (RR 0.41, 95% CI 0.21 to 0.82; 6 studies, 1166 participants; moderate-quality evidence). No studies reported on the effect of intermittent regimens versus daily regimens on iron deficiency anaemia and all-cause morbidity. Information on disease outcomes, adherence, economic productivity, and work performance was scarce, and evidence about the effects of intermittent supplementation on these outcomes unclear. Overall, whether the supplements were given once or twice weekly, for less or more than three months, contained less or more than 60 mg of elemental iron per week, or given to populations with different degrees of anaemia at baseline did not seem to affect the findings. Furthermore, the response did not differ in areas where malaria was frequent, although very few trials were conducted in these settings. Intermittent iron supplementation may reduce anaemia and may improve iron stores among menstruating women in populations with different anaemia and malaria backgrounds. In comparison with daily supplementation, the provision of iron supplements intermittently is probably as effective in preventing or controlling anaemia. More information is needed on morbidity (including malaria outcomes), side effects, work performance, economic productivity, depression, and adherence to the intervention. The quality of this evidence base ranged from very low to moderate quality, suggesting that we are uncertain about these effects.

We reviewed the evidence in February 2018. We included 25 randomised controlled trials (a type of experiment in which participants are randomly assigned to one or more treatment groups) involving 10,996 women. We included studies examining the administration of intermittent iron supplements versus no intervention, a placebo (dummy pill) or the same supplements given on a daily basis. Most studies were implemented in school settings and were mainly funded by international organisations, universities, and ministries of health within the countries. Approximately one-third of the included studies did not provide a funding source. The findings show that women receiving intermittent supplementation with iron alone, or in combination with folic acid or other nutrients, were less likely to be anaemic than those women who received no iron supplements or a placebo. They also had higher concentrations of haemoglobin and ferritin (a protein that carries iron). Intermittent supplementation also reduced the risk of having iron deficiency. The findings indicate that intermittent supplementation was as effective as daily supplementation in reducing the prevalence of anaemia and increasing haemoglobin concentrations, with fewer side effects. It had no effect on raising ferritin concentrations. We found scarce evidence on the effect of intermittent supplementation compared to placebo or daily supplementation on iron deficiency anaemia, all-cause morbidity, disease outcomes, adherence, economic productivity, and work performance. Intermittent iron supplementation in menstruating women may be an effective intervention for reducing anaemia and improving haemoglobin concentrations compared to no treatment, placebo or daily supplementation. Intermittent supplementation may be associated with fewer side effects compared to daily supplementation. The findings were not affected by whether the supplements were given once or twice weekly, for less or more than three months, contained less or more than 60 mg of elemental iron per week, or given to populations with different degrees of anaemia at baseline (starting point for comparisons). The evidence base was of overall low quality.

10.1002/14651858.CD009218.pub3

cochrane-simplification-train-3375

cochrane-simplification-train-3375

Fifteen trials (twelve parallel group studies; three crossover trials recruiting 1422 children (837 males and 585 females)) were included. The studies were generally of good methodological quality. Two large long term studies used nedocromil for six months and four to six years and showed conflicting results in symptom free days. Short term studies (duration between 4 weeks to 12 weeks) showed that nedocromil sodium produced some improvement in a number of efficacy measures compared to placebo including FEV1, FVC, FEV1 % predicted, PC20 FEV1, evening PEF and symptom scores. The parent's assessment of efficacy was in favour of nedocromil (odds ratio (OR) 0.5 (95% CI 0.3 to 0.8). Nedocromil sodium has a good safety profile. The only significant side effect observed was unpleasant taste. There was little evidence for a clinically dose response effect and only a few studies recruited participants with severe asthma. A limited number of small studies have shown that nedocromil is of benefit in improving lung function and some measures of symptoms, but the evidence with regard to the primary outcome of the review was conflicting. Two long-term trials did not show consistent effects on lung function outcomes, whereas several small short-term trials have shown benefit in these outcomes. Differing severities at baseline may explain this difference with milder participants experiencing less benefit, although the discrepancy between study findings may also reflect publication bias. Nedocromil sodium is associated with a very good safety profile with no significant short term or long- term adverse side effects. Although nedocromil may have advantages over inhaled corticosteroids in terms of side effects, there is a need for head to head trials of nedocromil and inhaled corticosteroids to establish whether asthma control is similar, especially in mild asthma. It is not yet clear where nedocromil should sit in relation to other therapies in the treatment of asthma in children.

The review of studies including 15 trials and 1422 children found that there were some encouraging results in short term studies when nedocromil was compared on its own with placebo, particularly with regard to lung function tests. However, these results were not confirmed in one large, longer term study of four to six years duration, which did not show significant difference in the primary outcome of symptom free days. This study was conducted in children who had mild asthma. There may be a role for nedocromil in the management of moderate asthma, but it should be assessed in relation to inhaled steroids, whose efficacy is well-established. This particularly important in symptomatic asthma.

10.1002/14651858.CD004108.pub2

cochrane-simplification-train-3376

cochrane-simplification-train-3376

Two studies (enrolling 118 participants) examined the association between intense hydration and ureteric colic outcomes. There was no significant difference in pain at six hours (1 study, 60 participants: RR 1.06, 95% CI 0.71 to 1.57), surgical stone removal (1 study, 60 participants: RR 1.20, 95% CI 0.41 to 3.51) or manipulation by cystoscopy (1 study, 60 participants: RR 0.67, 95% CI 0.21 to 2.13) when no fluids over six hours was compared to three litres IV fluids administered over a six hour period. There was no difference in stone clearance (1 study 43 participants: RR 1.38, 95% CI 0.50 to 3.84), hourly pain score or patients' narcotic requirements (P > 0.05 for all comparisons) when forced IV hydration of two litres over four hours was compared with minimal IV hydration at 20 mL/hour. One study did not provide any details which would have allowed us to assess any of the risk of bias items (selection, detection, performance, attrition or reporting bias). The second study did not report the method of randomisation or allocation (selection bias - unclear), they reported that the patients were blinded to therapy (low risk of bias), analgesics were administered according to predetermined pain score criteria (low risk), and assessment of stone passage was unlikely to have been biased by knowledge of group assignment (low risk). However the second study also reported a high percentage of participants excluded post randomisation (26%; high risk of bias). We were unable to assess or ascertain any of the other risk of bias items. We found no reliable evidence in the literature to support the use of diuretics and high volume fluid therapy for people with acute ureteric colic. However, given the potential positive therapeutic impact of fluids and diuretics to facilitate stone passage, the capacity of these interventions warrants further investigation to determine safety and efficacy profiles.

This review aimed to determine if increased fluids and diuretics or both could hasten the passage of stones and improve symptoms. Neither our initial review nor this subsequent update identified sufficient evidence to enable conclusions to be determined about the safety and effectiveness of increasing fluids or diuretics or both to treat people with acute ureteric colic. More and larger randomised controlled studies are required.

10.1002/14651858.CD004926.pub3

cochrane-simplification-train-3377

cochrane-simplification-train-3377

Two ITS studies, conducted between 1972 and 1984, met our inclusion criteria for the primary objective, and one study contributed to the quantitative analysis. This study was conducted in India, reported the incidence of malaria in four separate sites, and covered a total population of 18,460 people. In the pooled analysis across sites, there was no step effect for the incidence of uncomplicated malaria (step rate ratio 1.00, 95% confidence interval (CI) 0.51 to 1.92). There was an effect on the slope: the number of cases was reduced by 15% per month (slope rate ratio 0.85, 95% CI 0.79 to 0.91). Using these ratios, we estimated the effect of 12 months of space spraying on malaria incidence to be a reduction from 6 cases to 1 case per month per 1000 population (95% CI 0 to 2 cases, very low-certainty evidence). The second study reported the impact of space spraying on malaria incidence and adult mosquito density in a population of 15,106 in Haiti, but it did not provide data from previous years. Thus, we could not estimate an effect of space spraying that was independent from temporal trends. For the review's secondary objective, we identified a further two studies in addition to the two ITS studies; both used a CBA design and were conducted between 1973 and 2000. The four studies used a range of delivery methods including handheld, vehicle-mounted, and aircraft-mounted spraying equipment. A variety of insecticides, doses, and spraying times were also used, with methods typically determined based on environmental factors and vector profiles. Evidence from one state in India conducted over 30 years ago suggests an effect of space spraying on the incidence of malaria, but the certainty of the evidence is very low. Reliable research in a variety of settings will help establish whether and when this intervention may be worthwhile.

After searching for relevant trials up to 18 April 2018, we identified four studies conducted between 1972 and 2000. Across the four studies, a range of insecticide delivery methods were used, including handheld, vehicle-mounted, and aircraft-mounted spraying equipment. A variety of different insecticides, doses, and spraying times were also used to suit the local environment and the behaviour of the targeted mosquito species. In three studies, the evidence was considered to be unsuitable for reliably assessing the impact of space spraying on the number of cases of malaria. The remaining study, which took place in a single state in India and covered a combined population of 18,460 people, reported the number of malaria cases in the years preceding and following the introduction of space spraying. The evidence suggested that space spraying led to a decrease in the number of cases of malaria, but as the trial was conducted over 30 years ago and within one state in India, we cannot be certain that these findings are applicable in other areas where malaria occurs. Reliable research in a variety of settings will help to establish whether and when this intervention may be worthwhile.

10.1002/14651858.CD012689.pub2

cochrane-simplification-train-3378

cochrane-simplification-train-3378

165 trials were reviewed and eight were included; a total of 461 patients have been studied (229 with CBA; 232 with intermittent beta-agonists). Overall, admission to hospital was reduced with CBA compared to intermittent beta-agonists (RR: 0.68; 95% CI: 0.5 to 0.9); patients with severe airway obstruction at presentation appeared to benefit most from this intervention (RR: 0.64; 95% CI: 0.5 to 0.9). Patients receiving CBA demonstrated small but statistically significant improvements in pulmonary function tests when all studies were pooled. Patients receiving CBA had greater improvements in % predicted FEV-1 (SMD: 0.3; 95% CI: 0.03 to 0.5) and PEFR (SMD: 0.33; 95% CI: 0.1 to 0.5); this effect was observed by 2-3 hours. Continuous treatment was generally well tolerated, with no clinically important differences observed in pulse rate (WMD: -2.87; 95% CI: -6.0 to 0.3) or blood pressure (WMD: -1.75; 95% CI: -5.6 to 2.1) between the treatment groups. Tremor was equally common in both groups (OR: 0.81; 95% CI: 0.5 to 1.3) and potassium concentration was unchanged (WMD: 0.02; 95% CI: -0.2 to 0.2). Current evidence supports the use of CBA in patients with severe acute asthma who present to the emergency department to increase their pulmonary functions and reduce hospitalisation. Moreover, CBA treatment appears to be safe and well tolerated in patients who receive it.

This review has collected information from randomised controlled trials comparing continuous to intermittent nebulised delivery methods in acute asthma attacks. Overall, differences were found between the two methods, with continuous nebulisers producing a modest reduction in admissions compared to intermittent beta-agonist therapy. This finding was especially pronounced in severe acute asthma. Continuous nebuliser therapy may be more effective than intermittent nebulisers for delivering beta-agonist drugs to relieve airway spasm in selected asthma populations.

10.1002/14651858.CD001115

cochrane-simplification-train-3379

cochrane-simplification-train-3379

We included 17 trials, recruiting 2422 participants, for which outcome data are currently available. Participants tended to be a selected elderly group of stroke survivors with moderate disability. The ESD group showed reductions in the length of hospital stay equivalent to approximately six days (mean difference (MD) -5.5; 95% confidence interval (CI) -3 to -8 days; P < 0.0001; moderate-grade evidence). The primary outcome was available for 16 trials (2359 participants). Overall, the odds ratios (OR) for the outcome of death or dependency at the end of scheduled follow-up (median 6 months; range 3 to 12) was OR 0.80 (95% CI 0.67 to 0.95, P = 0.01, moderate-grade evidence) which equates to five fewer adverse outcomes per 100 patients receiving ESD. The results for death (16 trials; 2116 participants) and death or requiring institutional care (12 trials; 1664 participants) were OR 1.04 (95% CI 0.77 to 1.40, P = 0.81, moderate-grade evidence) and OR 0.75 (95% CI 0.59 to 0.96, P = 0.02, moderate-grade evidence), respectively. Small improvements were also seen in participants' extended activities of daily living scores (standardised mean difference (SMD) 0.14, 95% CI 0.03 to 0.25, P = 0.01, low-grade evidence) and satisfaction with services (OR 1.60, 95% CI 1.08 to 2.38, P = 0.02, low-grade evidence). We saw no clear differences in participants' activities of daily living scores, patients subjective health status or mood, or the subjective health status, mood or satisfaction with services of carers. We found low-quality evidence that the risk of readmission to hospital was similar in the ESD and conventional care group (OR 1.09, 95% CI 0.79 to 1.51, P = 0.59, low-grade evidence). The evidence for the apparent benefits were weaker at one- and five-year follow-up. Estimated costs from six individual trials ranged from 23% lower to 15% greater for the ESD group in comparison to usual care. In a series of pre-planned analyses, the greatest reductions in death or dependency were seen in the trials evaluating a co-ordinated ESD team with a suggestion of poorer results in those services without a co-ordinated team (subgroup interaction at P = 0.06). Stroke patients with mild to moderate disability at baseline showed greater reductions in death or dependency than those with more severe stroke (subgroup interaction at P = 0.04). Appropriately resourced ESD services with co-ordinated multidisciplinary team input provided for a selected group of stroke patients can reduce long-term dependency and admission to institutional care as well as reducing the length of hospital stay. Results are inconclusive for services without co-ordinated multidisciplinary team input. We observed no adverse impact on the mood or subjective health status of patients or carers, nor on readmission to hospital.

We identified 17 clinical trials recruiting 2422 stroke patients (searching completed to January 2017). Patients who were recruited tended to have a moderate degree of disability (able to walk with assistance) and be sufficiently well to consider returning home. We categorised services as those based on a multidisciplinary ESD team (with different levels of co-ordination and delivery) and those with no multidisciplinary team co-ordination (no ESD team). The length of initial stay in hospital was reduced by approximately five days for the ESD group. At an average of six months after their stroke ESD patients were more likely to be living at home (an extra five patients living at home for every 100 receiving ESD services; moderate-quality evidence). They were also more likely to be independent in daily activities (an extra six patients independent for every 100 receiving ESD services; moderate-quality evidence). We identified no apparent hazards in terms of patient mood or quality of life, carer mood or quality of life, or the risk of readmission to hospital. The greatest reductions in disability seemed to be present in trials based around a co-ordinated ESD team. When compared with usual care, costs of ESD services ranged from a reduction to a modest increase. The quality of the evidence was downgraded to 'moderate' for the main outcomes of death, discharge home or disability. This was because it was impossible to hide the treating service from participants or healthcare workers. These conclusions were not dependent on trials judged to be lower quality because of poor design or missing data. More information was missing for some of the other outcome measures, which we have downgraded to low-quality evidence. Appropriately resourced ESD services with co-ordinated multidisciplinary team input can reduce disability and the length of time in hospital at least for a selected group of people with stroke. Results are unclear for services that are not based on a co-ordinated multidisciplinary team input. We did not identify any substantial harmful effects.

10.1002/14651858.CD000443.pub4

cochrane-simplification-train-3380

cochrane-simplification-train-3380

We identified 83 publications and 29 were included, representing 15 data sets (475 participants). There was insufficient evidence to confirm or exclude any differences, between CCPT and other airway clearance techniques in terms of respiratory function measured by standard lung function tests. Studies undertaken during acute exacerbations demonstrated relatively large gains in respiratory function irrespective of airway clearance technique. Longer-term studies demonstrated smaller improvements or deterioration over time. Ten studies reported individual preferences for technique, with participants tending to favour self-administered techniques. Heterogeneity in the measurement of preference precluded these data from meta-analysis. This review was unable to demonstrate any advantage of CCPT over other airway clearance techniques in terms of respiratory function, but this may have reflected insufficient evidence rather than real equivalence between methods. There was a trend for participants to prefer self-administered airway clearance techniques. Limitations of this review included a paucity of well-designed, adequately-powered, long-term trials.

We looked for studies lasting over one week. We included fifteen studies in the review. These studies did not show any difference between chest physiotherapy and other therapies in terms of lung function. Studies of acute infections showed improved lung function irrespective of type of treatment. Longer-term studies showed smaller improvements or decline. In ten studies participants preferred techniques they administered on themselves. The review was limited by the lack of well-designed long-term trials. We did not find evidence that conventional chest physiotherapy techniques were any better than other treatments for lung function. We can not recommend any single treatment over another at this time.

10.1002/14651858.CD002011.pub2

cochrane-simplification-train-3381

cochrane-simplification-train-3381

Five studies with a total of 105 participants were found to be eligible for inclusion in this review. All included trials were short-term studies (two days or less), measuring immediate effects of the interventions. There was insufficient detail in the reports to assess methods of randomisation and allocation concealment. All five studies were at a high risk of bias from lack of blinding. The studies did not report on mortality, morbidity, quality of life, serious adverse events or any of the other prespecified outcomes. One study was a randomised cross-over trial conducted over two days, in which investigators applied two interventions twice daily in randomly assigned order, with a reverse cross-over the following day. Four studies applied multiple interventions for cough augmentation to each participant, in random order. One study reported fatigue as an adverse effect of MI-E, using a visual analogue scale. Peak cough expiratory flow (PCEF) was the most common outcome measure and was reported in four studies. Based on three studies, MI-E may improve PCEF compared to an unassisted cough. All interventions increased PCEF to the critical level necessary for mucus clearance. The included studies did not clearly show that MI-E improves cough expiratory flow more than other cough augmentation techniques. Based on one study, which was at risk of assessor bias, the addition of MI-E may reduce treatment time when added to a standard airway clearance regimen with manually assisted cough. MI-E appeared to be as well tolerated as other cough augmentation techniques, based on three studies which reported comfort visual analogue scores. The results of this review do not provide sufficient evidence on which to base clinical practice as we were unable to address important short- and long-term outcomes, including adverse effects of MI-E. There is currently insufficient evidence for or against the use of MI-E in people with NMDs. Further randomised controlled clinical trials are needed to test the safety and efficacy of MI-E.

We found five trials, with 105 people. They all studied the immediate effects of a single treatment with MI-E. The studies compared MI-E to other ways of helping people cough, or normal cough without help. One trial studied MI-E when added to other treatment. Based on three trials, MI-E may improve the outwards flow of air during coughing compared to a normal cough without help. MI-E was not clearly better than other methods of improving cough. None of the studies measured the outcomes that we thought were important for making decisions about the usefulness of MI-E. For example, the studies did not report on survival, length of hospital stay, quality of life, or serious side effects. One study reported extreme tiredness as a side effect of MI-E. There was often not enough information in the reports to tell whether the studies were well run; in some we found design problems that could have affected the results. The findings of this review do not give enough evidence on which to make decisions. We were unable to find any information from trials on important short- and long-term effects, including side effects of MI-E in NMDs. There is currently insufficient evidence for or against the use of MI-E to help people with NMDs clear mucus from their lungs. Further studies are needed to better understand the benefits and risks of MI-E in relation to other methods of cough assistance. The evidence in the review is up to date as of 7 October 2013.

10.1002/14651858.CD010044.pub2

cochrane-simplification-train-3382

cochrane-simplification-train-3382

Twenty-one trials, involving 22,129 women were eligible for this review. Four trials did not contribute data. All of the remaining 17 trials assessed vitamin E in combination with vitamin C and/or other agents. Overall the risk of bias ranged from low to unclear to high; 10 trials were judged to be at low risk of bias, six trials to be at unclear risk of bias and five trials to be at high risk of bias. No clear difference was found between women supplemented with vitamin E in combination with other supplements during pregnancy compared with placebo for the risk of stillbirth (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.88 to 1.56, nine studies, 19,023 participants, I² = 0%; moderate quality evidence), neonatal death (RR 0.81, 95% CI 0.58 to 1.13, nine trials, 18,617 participants, I² = 0%), pre-eclampsia (average RR 0.91, 95% CI 0.79 to 1.06; 14 trials, 20,878 participants; I² = 48%; moderate quality evidence), preterm birth (average RR 0.98, 95% CI 0.88 to 1.09, 11 trials, 20,565 participants, I² = 52%; high quality evidence) or intrauterine growth restriction (RR 0.98, 95% CI 0.91 to 1.06, 11 trials, 20,202 participants, I² = 17%; high quality evidence). Women supplemented with vitamin E in combination with other supplements compared with placebo were at decreased risk of having a placental abruption (RR 0.64, 95% CI 0.44 to 0.93, seven trials, 14,922 participants, I² = 0%; high quality evidence). Conversely, supplementation with vitamin E was associated with an increased risk of self-reported abdominal pain (RR 1.66, 95% CI 1.16 to 2.37, one trial, 1877 participants) and term prelabour rupture of membranes (PROM) (average RR 1.77, 95% CI 1.37 to 2.28, two trials, 2504 participants, I² = 0%); however, there was no corresponding increased risk for preterm PROM (average RR 1.27, 95% CI 0.93 to 1.75, five trials, 1999 participants, I² = 66%; low quality evidence). There were no clear differences between the vitamin E and placebo or control groups for any other maternal or infant outcomes. There were no clear differing patterns in subgroups of women based on the timing of commencement of supplementation or baseline risk of adverse pregnancy outcomes. The GRADE quality of the evidence was high for preterm birth, intrauterine growth restriction and placental abruption, moderate for stillbirth and clinical pre-eclampsia, and low for preterm PROM. The data do not support routine vitamin E supplementation in combination with other supplements for the prevention of stillbirth, neonatal death, preterm birth, pre-eclampsia, preterm or term PROM or poor fetal growth. Further research is required to elucidate the possible role of vitamin E in the prevention of placental abruption. There was no convincing evidence that vitamin E supplementation in combination with other supplements results in other important benefits or harms.

This review included 21 trials involving over 21,000 women. Four trials did not contribute data to the analyses. The trials were generally of variable quality. There were just three studies on vitamin E supplementation alone, but none of these studies contributed data. All other studies included vitamin C, and additional supplements or drugs. The findings indicate that routine supplementation with vitamin E in combination with other supplements during pregnancy did not improve outcomes for babies or women. There was a reduction in the number of placentas coming away early (placental abruption) in women given vitamin E supplements in combination with other agents, which was rated as high-quality evidence. However, it is unclear whether this finding was due to vitamin E or the other agents used in the supplement. This should be explored in further research examining the mechanisms leading to placental abruption. The review found there may be harms associated with vitamin E supplements in pregnancy, as there was an increased risk of abdominal pain and term prelabour rupture of fetal membranes in women supplemented with vitamin E in combination with other supplements. There was no increase in preterm prelabour rupture of membranes in women supplemented with vitamin E and other agents. The large body of evidence does not support taking vitamin E supplements, alone or in combination, during pregnancy. This is because taking vitamin E in combination with other supplements during pregnancy does not help to prevent problems in pregnancy including stillbirth, baby death, preterm birth, pre-eclampsia or low birthweight babies. In fact, it may increase abdominal pain for women and also increase the number of women having early rupture of membranes at term.

10.1002/14651858.CD004069.pub3

cochrane-simplification-train-3383

cochrane-simplification-train-3383

Four studies met all of the inclusion criteria (with a total of 40 participants). Three subclasses of anxiety medications were used including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and azapirones. Although two studies used SSRIs as the intervention (total of 21 participants), we were unable to meta-analyse the anxiety outcomes as one study had a standard deviation of zero for the control group. Included studies had relatively poor quality including small sample sizes and short follow-up periods. Due to the small number of included studies, we were unable to meta-analyse all the subclasses of medications. Due to the sub-optimal quality of the trials and statistically non-significant results, it is not possible to draw any conclusions for treatment. This review highlights the paucity of data in this area. As such, there is a need for scientifically rigorous research trials to evaluate the role of pharmacological interventions for anxiety disorders in patients with COPD, using a sample size large enough to demonstrate meaningful clinical significance.

This systematic review of four studies (total of 40 participants) found insufficient evidence of benefit for any of the three classes of medications included in this review. There is a considerable lack of evidence to address pharmacological interventions for anxiety disorders in patients with COPD. We recommend that new research be conducted to ascertain the best mode of treatment for anxiety within this population. This new research needs to be of good methodological design, investigate an adequate number of patients and have a meaningful length of follow-up.

10.1002/14651858.CD008483.pub2

cochrane-simplification-train-3384

cochrane-simplification-train-3384

We included 17 studies, with a total of 1025 participants; 12 studies were published (567 patients) and five were unpublished (458 patients). Sixteen studies including 953 people compared betahistine with placebo. All studies with analysable data lasted three months or less. The majority were at high risk of bias, but in some the risk of bias was unclear. One study, at high risk of bias, included 72 people with benign paroxysmal positional vertigo (BPPV) and compared betahistine with placebo; all patients also had particle repositioning manoeuvres. The studies varied considerably in terms of types of participants, their diagnoses, the dose of betahistine and the length of time it was taken for, the study methods and the way any improvement in vertigo symptoms was measured. Using the GRADE system, we judged the quality of evidence overall to be low for two outcomes (proportion of patients with improvement and proportion with adverse events). Pooled data showed that the proportion of patients reporting an overall reduction in their vertigo symptoms was higher in the group treated with betahistine than the placebo group: risk ratio (RR) 1.30, 95% confidence interval (CI) 1.05 to 1.60; 606 participants; 11 studies). This result should be interpreted with caution as the test for statistical heterogeneity as measured by the I2 value was high. Adverse effects (mostly gastrointestinal symptoms and headache) were common but medically serious events in the study were rare and isolated: there was no difference in the frequency of adverse effects between the betahistine and placebo groups, where the rates were 16% and 15% respectively (weighted values, RR 1.03, 95% CI 0.76 to 1.40; 819 participants; 12 studies). Sixteen per cent of patients from both the betahistine and the placebo groups withdrew (dropped out) from the studies (RR 0.96, 95% CI 0.65 to 1.42; 481 participants; eight studies). Three studies looked at objective vestibular function tests as an outcome; the numbers of participants were small, techniques of measurement very diverse and reporting details sparse, so analysis of this outcome was inconclusive. We looked for information on generic quality of life and falls, but none of the studies reported on these outcomes. Low quality evidence suggests that in patients suffering from vertigo from different causes there may be a positive effect of betahistine in terms of reduction in vertigo symptoms. Betahistine is generally well tolerated with a low risk of adverse events. Future research into the management of vertigo symptoms needs to use more rigorous methodology and include outcomes that matter to patients and their families.

We included 17 studies, with a total of 1025 participants. Sixteen studies including 953 people compared betahistine with placebo; the studies were at high to unclear risk of bias. All studies with analysable data lasted three months or less. One study, at high risk of bias, included 72 people with benign paroxysmal positional vertigo (BPPV) and compared betahistine with placebo; all patients also had particle repositioning manoeuvres. We judged the quality of evidence overall to be low. The studies varied considerably in terms of types of participants, their diagnoses, the dose of betahistine and the length of time the drug was taken for, the study methods and the way any improvement in vertigo symptoms was measured. When all studies are taken together, the proportion of patients reporting a reduction of their vertigo symptoms was significantly higher in the betahistine group than in the placebo group. However, there was significant variability in the results of the studies so this result should be treated with caution. The proportion of patients reporting side effects of the medication was similar in both groups: 16% in the betahistine groups and 15% in the placebo groups. Overall, 16% of patients of both groups withdrew from the studies. There was insufficient information about the effect of betahistine on objective tests of inner ear balance organ function. There was no information on the effect of betahistine on overall quality of life or falls. We judged the quality of evidence from the included studies to be low, meaning our estimates of the effects of betahistine could turn out to be inaccurate. The evidence is up to date to September 2015. Low quality evidence suggests that patients suffering from vertigo from different causes may have some benefit from betahistine in terms of reduction in vertigo symptoms. Betahistine is generally well tolerated. Future research into the management of vertigo symptoms needs to use more rigorous methodology and include outcomes that matter to patients and their families.

10.1002/14651858.CD010696.pub2

cochrane-simplification-train-3385

cochrane-simplification-train-3385

Twenty-two studies were included in the review: 16 RCTs, two non-RCTs, one partially randomised trial that contained two randomised intervention arms and one non-randomised control arm, two CBA studies, and one quasi-randomised controlled trial. Seventeen studies provided interventions comprising parenting education and other support services, 15 of which were home visiting programmes and two of which were paediatric practice-based interventions. Two provided solely educational interventions. Nineteen studies recruited families who were from socio-economically disadvantaged populations who were at risk of adverse child outcomes or people who may benefit from extra support, such as single mothers, teenage mothers, first-time mothers, and mothers with learning difficulties. Ten RCTs involving 5074 participants were included in the meta-analysis, which indicated that intervention families had a statistically significant lower risk of injury than control families (RR 0.83, 95% confidence interval (CI) 0.73 to 0.94). Sensitivity analyses undertaken that included only RCTs at low risk of various sources of bias found the findings to be robust to including only those studies at low risk of detection bias in terms of blinded outcome assessment and attrition bias in terms of follow-up of fewer than 80% of participants in each arm. When analyses were restricted to studies at low risk of selection bias in terms of inadequate allocation concealment, the effect size was no longer statistically significant. Several studies found statistically significantly fewer home hazards or a greater number of safety practices in intervention families. Of ten studies reporting scores on the HOME scale, data from three RCTs were included in a meta-analysis, which found no evidence of a difference in quality of the home environment between treatment arms (mean difference 0.57, 95% CI -0.59 to 1.72). Most of the studies reporting home safety practices, home hazards, or composite home safety scores found statistically significant effects favouring intervention arm families. Overall, when Grading of Recommendations Assessment, Development, and Evaluation guidelines (GRADE) were used, the quality of the evidence was rated as moderate. Parenting interventions, most commonly provided within the home using multi-faceted interventions, are effective in reducing child injury. Fairly consistent evidence suggests that they also improve home safety. This evidence relates mainly to interventions provided to families from disadvantaged populations, who are at risk of adverse child health outcomes, or whose families may benefit from extra support. Further research is required to explore mechanisms by which these interventions may reduce injury, to identify the features of parenting interventions that are necessary or sufficient to reduce injury, and to assess the generalisability of these findings to different population groups.

Through searches of databases and web sites, we found 22 randomised and non-randomised studies that evaluated the effects of parenting programmes on childhood injuries or home safety. Fifteen of these were home visiting programmes that provided a range of support services, as well as parent education or training. These programmes were usually provided to families who were disadvantaged, whose children were considered to be at risk of poor health, or who may benefit from extra support. We pooled the results from 10 randomised controlled trials, which included a total of 5074 children, and found that children from families who had completed the parenting programmes had sustained fewer injuries than those from families who had not attended the programmes. We pooled the results from three randomized controlled trials that measured home safety using the Home Observation for Measurement of the Environment (HOME) tool. The results from these three studies, which included a total of 368 children, showed no difference in HOME scores between families receiving parenting programmes and those not receiving these programmes. Overall, the quality of the studies was reasonable. We conclude that parenting programmes are effective in reducing unintentional injury in children and can improve home safety, particularly in families who may be considered 'at risk,' such as some teenage or single mothers. It would be worthwhile for health and social care providers to make parenting programmes available to families.

10.1002/14651858.CD006020.pub3

cochrane-simplification-train-3386

cochrane-simplification-train-3386

We identified three randomised controlled trials (RCTs) of rhIGF-I, involving 779 participants, for inclusion in the analysis. In a European trial (183 participants) the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08). In a North American trial (266 participants), the MD after nine months was -6.00 (95% CI -10.99 to -1.01). The combined analysis from both RCTs showed a MD after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. There was an increased risk of injection site reactions with rhIGF-I (risk ratio 1.26, 95% CI 1.04 to 1.54). . A second North American trial (330 participants) used a novel primary end point involving manual muscle strength testing. No differences were demonstrated between the treated and placebo groups in this study. All three trials were at high risk of bias. Meta-analysis revealed a significant difference in favour of rhIGF-I treatment; however, the quality of the evidence from the two included trials was low. A third study showed no difference between treatment and placebo. There is no evidence for increase in survival with IGF1. All three included trials were at high risk of bias.

Three randomised controlled trials (RCTs) involving 779 participants measured disease progression on special clinical rating scales of disease severity in ALS. The review authors collected data about adverse events from the included trials. The combined results from the two included studies that used the rating scale (AALSRS) showed a small significant benefit in favour of rhIGF-I. Significant flaws in the trial designs make the statistically significant benefits in some outcomes of questionable relevance. There was an increased risk of injection site reactions with rhIGF-I. A third study using a different outcome measure showed no difference between treatment and placebo. Taken together, the available RCTs do not provide information supporting the hypothesis that rhIGF-I is an effective disease modifying treatment for ALS. All three included studies showed a high risk of bias. These issues very seriously detracted from the ability of this review to fulfil its objectives.

10.1002/14651858.CD002064.pub3

cochrane-simplification-train-3387

cochrane-simplification-train-3387

Eighteen trials were included, involving a total of 10,049 participants. Trials differed considerably in their inclusion criteria, outcomes measured, and type of lipid-lowering therapy used. Only one trial (PQRST) reported a detrimental effect of active treatment on blood lipid/lipoprotein levels. The pooled results from all eligible trials indicated that lipid-lowering therapy had no statistically significant effect on overall mortality (Odds Ratio (OR) 0.86; 95% Confidence Interval (CI) 0.49 to 1.50) or on total cardiovascular events (OR 0.8; 95% CI 0.59 to 1.09). However, subgroup analysis which excluded PQRST showed that lipid-lowering therapy significantly reduced the risk of total cardiovascular events (OR 0.74; CI 0.55 to 0.98). This was primarily due to a positive effect on total coronary events (OR 0.76; 95% CI 0.67 to 0.87). Greatest evidence of effectiveness came from the use of simvastatin in people with a blood cholesterol ≥ 3.5 mmol/litre (HPS). Pooling of the results from several small trials on a range of different lipid-lowering agents indicated an improvement in total walking distance (Mean Difference (MD) 152 m; 95% CI 32.11 to 271.88) and pain-free walking distance (WMD 89.76 m; 95% CI 30.05 to 149.47) but no significant impact on ankle brachial index (WMD 0.04; 95% CI -0.01 to 0.09). Lipid-lowering therapy is effective in reducing cardiovascular mortality and morbidity in people with PAD. It may also improve local symptoms. Until further evidence on the relative effectiveness of different lipid-lowering agents is available, use of a statin in people with PAD and a blood cholesterol level ≥ 3.5 mmol/litre is most indicated.

Eighteen randomised controlled trials were included in the review, involving a total of 10,049 participants (78% were men) from seven different countries. The trials compared lipid-lowering therapy with placebo or usual treatment for at least 90 days. They differed considerably in the inclusion criteria, outcomes measured, and type of lipid-lowering therapy used. Lipid-lowering therapies improved walking distance. The effect of lipid-lowering therapy on death from any cause in people with peripheral artery disease was inconclusive. Using drugs to lower blood lipids had a beneficial effect on the incidence of total cardiovascular events, due primarily to an overall reduction in coronary events (OR 0.8; 95% Confidence Interval 0.7 to 0.9). The only type of drug for which consistent, clear evidence of a beneficial effect on total cardiovascular events, total coronary events and stroke was available, was the statins. The greatest evidence was with simvastatin in people with a blood cholesterol level of at least 3.5 mmol/litre. The evidence on side effects was inconclusive in these trials.

10.1002/14651858.CD000123.pub2

cochrane-simplification-train-3388

cochrane-simplification-train-3388

Five trials (612 women) met the inclusion criteria. Only three trials (404 women) provided data that were suitable for analysis. Combined oral contraceptive pill versus placebo Two trials compared COCP with a placebo. These studies were at high risk of bias. For GRADE outcomes (self-reported pain (dysmenorrhoea) at the end of treatment), the quality of the evidence very low. Evidence was downgraded for imprecision as it was based on a single, small trial and for the visual analogue scale data there were wide confidence intervals (CIs). There appeared to have been substantial involvement of the pharmaceutical company funding the trials. Treatment with the COCP was associated with an improvement in self-reported pain at the end of treatment as evidenced by a lower score on the Dysmenorrhoea verbal rating scale (scale 0 to 3) compared with placebo (mean difference (MD) -1.30 points, 95% CI -1.84 to -0.76; 1 RCT, 96 women; very low quality evidence), a lower score on the Dysmenorrhoea visual analogue scale (no details of scale) compared with placebo (MD -23.68 points, 95% CI -28.75 to -18.62, 2 RCTs, 327 women; very low quality evidence) and a reduction in menstrual pain from baseline to the end of treatment (MD 2.10 points, 95% CI 1.38 to 2.82; 1 RCT, 169 women; very low quality evidence). Combined oral contraceptive pill versus medical therapies One underpowered trial compared the COCP with another medical treatment (goserelin). The study was at high risk of bias; the trial was unblinded and there was insufficient detail to judge allocation concealment and randomisation. For GRADE outcomes (self-reported pain (dysmenorrhoea) at the end of treatment), the quality of the evidence ranged from low to very low. At the end of treatment, the women in the goserelin group were amenorrhoeic and therefore no comparisons could be made between the groups for the primary outcome. At six months' follow-up, there was no clear evidence of a difference between women treated with the COCP and women treated with goserelin for measures of dysmenorrhoea on a visual analogue scale (scale 1 to 10) (MD -0.10, 95% CI -1.28 to 1.08; 1 RCT, 50 women; very low quality evidence) or a verbal rating scale (scale 0 to 3) (MD -0.10, 95% CI -0.99 to 0.79; 1 RCT, 50 women; very low quality evidence). At six months' follow-up, there was no clear evidence of a difference between the COCP and goserelin groups for reporting complete absence of pain as measured by the visual analogue scale (risk ratio (RR) 0.36, 95% CI 0.02 to 8.43; 1 RCT, 50 women; very low quality evidence) or the verbal rating scale (RR 1.00, 95% CI 0.93 to 1.08; 1 RCT, 49 women; low quality evidence). Based on the limited evidence from two trials at high risk of bias and limited data for the prespecified outcomes for this review, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with placebo and the findings cannot be generalised. Based on the limited evidence from one small trial that was at high risk of bias, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with other medical treatments. Only one comparison was possible, with the medical intervention being goserelin, and the findings cannot be generalised. Further research is needed to fully evaluate the role of COCPs in managing pain-related symptoms associated with endometriosis. There are other formulations of the combined hormonal contraception such as the transdermal patch, vaginal ring or combined injectable contraceptives which this review did not cover but should be considered in future updates.

Cochrane authors searched for clinical studies on 19 October 2017. We found five trials, including 612 women, that met the inclusion criteria. The studies took place in Egypt, the US, Japan and Italy. Only three of the included studies provided data in a format that could be analysed in this review. Combined oral contraceptive pill versus placebo We found two trials including 354 women that compared the COCP with a placebo (pretend treatment). The evidence was at high risk of bias. There was very low quality evidence that treatment with the COCP was associated with an improvement in self-reported dysmenorrhoea (period pain) at the end of treatment measure on a verbal rating scale (where the woman rates her pain as (for example) "no pain," "slight pain," "moderate pain," "severe pain" and "unbearable pain") and low quality evidence for an improvement in self-reported dysmenorrhoea pain at the end of treatment using a visual rating scale (where the woman marks her pain visually on a line) compared with placebo. There was very low quality evidence that there was a reduction in menstrual pain from the beginning to the end of treatment in the COCP group compared with women having a placebo. Combined oral contraceptive pill versus other medical treatment We found one trial of 50 women that compared the COCP with another medical treatment (goserelin). The study was at high risk of bias. At the end of treatment, the women in the goserelin group were not having a period and therefore we could not compare the groups. Six months after the end of treatment, there was very low quality evidence that there was no clear difference between women treated with the COCP and women treated with goserelin for self-reported dysmenorrhoea, using a visual rating scale or a verbal rating scale. Six months after the end of treatment, there was very low quality evidence that there was no clear evidence of a difference between the COCP and goserelin groups for reporting complete absence of pain, as measured by a visual rating scale and low quality evidence using a verbal rating scale. The quality of the evidence was very low quality. The main reasons for downgrading the evidence were because the data were based on a single small trial with wide variation in results and lack of details about how the study had been designed. There were some concerns with two of the studies that were funded by a pharmaceutical company that also had input into the design of the trial, data collection and the analysis of data. This means that we cannot be confident about the results.

10.1002/14651858.CD001019.pub3

cochrane-simplification-train-3389

cochrane-simplification-train-3389

A total of 2306 references were found from our searches, 61 of which were identified as potential trials comparing surgery and sclerotherapy. However, only nine randomised trials, described in a total of 14 separate papers, fulfilled the inclusion criteria. Fifty trials were excluded and one trial is ongoing and is due for completion in 2004. The trials used a variety of outcome measures and classification systems which made direct comparison between trials difficult. However, the trend was for sclerotherapy to be evaluated as significantly better than surgery at one year; after one year (sclerotherapy resulted in worse outcomes) the benefits with sclerotherapy were less, and by three to five years surgery had better outcomes. The data on cost-effectiveness was not adequately reported. There was insufficient evidence to preferentially recommend the use of sclerotherapy or surgery. There needs to be more research that specifically examines both costs and outcomes for surgery and sclerotherapy.

This review found that sclerotherapy was better than surgery in terms of treatment success, complication rate and cost at one year, but surgery was better after five years. However, the evidence was not of very good quality and more research is needed.

10.1002/14651858.CD004980

cochrane-simplification-train-3390

cochrane-simplification-train-3390

We identified two small trials (Alexander 1991and Nishikawa 1996 which fulfilled the inclusion criteria, (total n=17, duration 3-6 weeks). Few data were reported and, because of inappropriate use of crossover methodology, we could not include all of the data in this review. For the few chronically ill people in these trials, neither the 'active' tetracycline bacteriostatic agent, oral demeclocycline, nor the opiate antagonist naloxone, nor placebo, gave any suggestion of serious adverse effects for a period of up to six weeks. The studies did not report any useful data on measures of polydipsia, physical symptoms secondary to increased fluid intake, mental state, general functioning or economic outcomes. The trials offer little useful data to the clinician hoping to treat psychosis-related polydipsia with drugs, except that further evaluative studies need to be conducted in this area. Treatment of any sort for psychosis related polydipsia might only be informative within a well designed, conducted and reported randomised study. The two pioneering studies suggest that larger trials, though difficult, would not be impossible with adequate support and co-ordination.

We systematically searched and evaluated randomised controlled trials investigating the effectiveness of drug treatment for polydipsia. We found two short trials (n=17, duration 3-6 weeks) that were too small and short to be informative. Data reporting was also poor with no pre crossover data available for analysis. The only data available were for adverse effects and neither the active treatments nor placebo produced any serious side effects. The studies did not report any useful data on measures of polydipsia, physical symptoms secondary to increased fluid intake, mental state, general functioning or economic outcomes. Clinicians hoping to treat people with psychosis-related polydipsia are unable to gain any useful information from these trials and treatment of any sort might only be informative within a well-designed study. More research is needed and these two trials, although unable to provide much data, do show this type of research is possible.

10.1002/14651858.CD003544.pub2

cochrane-simplification-train-3391

cochrane-simplification-train-3391

We found 55 trials (163,471 participants) with a median duration of 12 month follow up. Fourteen trials (139,256 participants) with reported clinical event endpoints, the pooled ORs for total and CHD mortality were 1.00 (95% CI 0.96 to 1.05) and 0.99 (95% CI 0.92 to 1.07), respectively. Total mortality and combined fatal and non-fatal cardiovascular events showed benefits from intervention when confined to trials involving people with hypertension (16 trials) and diabetes (5 trials): OR 0.78 (95% CI 0.68 to 0.89) and OR 0.71 (95% CI 0.61 to 0.83), respectively. Net changes (weighted mean differences) in systolic and diastolic blood pressure (53 trials) and blood cholesterol (50 trials) were -2.71 mmHg (95% CI -3.49 to -1.93), -2.13 mmHg (95% CI -2.67 to -1.58 ) and -0.24 mmol/l (95% CI -0.32 to -0.16), respectively. The OR for reduction in smoking prevalence (20 trials) was 0.87 (95% CI 0.75 to 1.00). Marked heterogeneity (I2 > 85%) for all risk factor analyses was not explained by co-morbidities, allocation concealment, use of antihypertensive or cholesterol-lowering drugs, or by age of trial. Interventions using counselling and education aimed at behaviour change do not reduce total or CHD mortality or clinical events in general populations but may be effective in reducing mortality in high-risk hypertensive and diabetic populations. Risk factor declines were modest but owing to marked unexplained heterogeneity between trials, the pooled estimates are of dubious validity. Evidence suggests that health promotion interventions have limited use in general populations.

This review is an update of all relevant randomised trials that have evaluated an intervention that aimed to reduce more than one risk factor (multiple risk factor intervention) in people without evidence of cardiovascular disease. The findings are from 55 trials of between six months and 12 years duration conducted in several countries over the course of four decades. The median duration of follow up was 12 months (with a range of six months to 12 years). Multiple risk factor intervention does result in small reductions in risk factors including blood pressure, cholesterol and smoking. Contrary to expectations, multiple risk factor interventions had little or no impact on the risk of coronary heart disease mortality or morbidity. This could be because these small risk factor changes were not maintained in the long term. Alternatively, the small reductions in risk factors may be caused by biases in some of the studies. The methods of attempting behaviour change in the general population are limited and do not appear to be effective. Different approaches to behaviour change are needed and should be tested empirically before being widely promoted, particularly in developing countries where cardiovascular disease rates are rising. Further trials may be warranted.

10.1002/14651858.CD001561.pub3

cochrane-simplification-train-3392

cochrane-simplification-train-3392

Six trials involving 159 patients satisfied the inclusion criteria. Data could not be analysed from one trial due to changes in patient numbers and from a second because the data provided were not in a usable format. All trials reported intelligibility measures but a statistically significant result was only reported for the diagnostic rhyme test used in the study of Lee Silverman Voice Treatment -LOUD (LSVT-LOUD) versus a modified version of this therapy (LSVT-ARTIC). In this case a difference of 12.5 points (95% confidence interval (CI) -22.2 to -2.8; P = 0.01) between the mean changes in favour of the LSVT-LOUD group was reported for a speech sample overlaid with Babble noise; this difference was not reproduced for the two additional noise conditions under which the speech samples were assessed. LSVT-LOUD also outperformed LSVT-ARTIC and Respiration therapy (RT) in improving loudness, with a difference in reading a sample text of 5.0 dB (95%CI -8.3 to -1.7; P = 0.003) and 5.5 dB (95% CI 3.4 to 7.7; P < 0.00001) respectively, and a difference in monologue speech of 2.9 dB (95% CI 0.6 to 5.2; P = 0.01) versus RT. Considering the small patient numbers in these trials, there is insufficient evidence to support or refute the efficacy of any form of SLT over another to treat speech problems in patients with Parkinson's disease.

Only randomised controlled trials were included in this review. These are studies in which two groups of patients were compared, each group receiving a different form of SLT, with patients assigned to the groups in a random fashion to reduce potential for bias. Six trials were found with a total of 159 patients. Methods varied so much that meta-analysis of the results was not possible. Considering the small number of patients and the methodological flaws in these studies, there is insufficient evidence to support the use of one form of SLT over another for the treatment of speech problems in individuals with Parkinson's disease.

10.1002/14651858.CD002814.pub2

cochrane-simplification-train-3393

cochrane-simplification-train-3393

Thirty-four trials (1314 participants) were included: fifteen in the empirical treatment group, fifteen in the ENRD group and four in both. In empirical treatment of GORD the risk ratio (RR) for heartburn remission (the primary efficacy variable) in placebo-controlled trials for PPI was 0.37 (two trials, 95% confidence interval (CI) 0.32 to 0.44), for H2RAs 0.77 (two trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (one trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were more effective than H2RAs (seven trials, RR 0.66, 95% CI 0.60 to 0.73) and prokinetics (two trials, RR 0.53, 95% CI 0.32 to 0.87). In treatment of ENRD, the RR for heartburn remission for PPI versus placebo was 0.71 (ten trials, 95% CI 0.65 to 0.78) and for H2RA versus placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.78 (three trials, 95% CI 0.62 to 0.97) and for PPI versus prokinetic 0.72 (one trial, 95% CI 0.56 to 0.92). PPIs are more effective than H2RAs in relieving heartburn in patients with GORD who are treated empirically and in those with ENRD, although the magnitude of benefit is greater for those treated empirically.

This review found that in the short term PPIs relieve heartburn better than H2RAs in patients who are treated without specific diagnostic testing. Although the difference is smaller, this is also true for patients with gastro-oesophageal reflux disease (GORD), who have a normal upper endoscopy . In summary, proton pump inhibitor drugs appear to be more effective than H2-receptor antagonists for relieving heartburn.

10.1002/14651858.CD002095.pub5

cochrane-simplification-train-3394

cochrane-simplification-train-3394

Five paediatric (parallel group or cross-over) trials met the inclusion criteria. We considered two (40%) trials to be at a low risk of bias. Four published trials, representing 559 children (aged ≥ six years) and adolescents with mild to moderate asthma, contributed data to the review. No trial enrolled preschoolers. All trials used montelukast as the anti-leukotriene agent administered for between four and 16 weeks. Three trials evaluated the combination of anti-leukotrienes and ICS compared to the same dose of ICS alone (step 3 versus step 2). No statistically significant group difference was observed in the only trial reporting participants with exacerbations requiring oral corticosteroids over four weeks (N = 268 participants; risk ratio (RR) 0.80, 95% confidence interval (CI) 0.34 to 1.91). There was also no statistically significant difference in percentage change in FEV₁ (forced expiratory volume in 1 second) with mean difference (MD) 1.3 (95% CI -0.09 to 2.69) in this trial, but a significant group difference was observed in the morning (AM) and evening (PM) peak expiratory flow rates (PEFR): N = 218 participants; MD 9.70 L/min (95% CI 1.27 to 18.13) and MD 10.70 (95% CI 2.41 to 18.99), respectively. One trial compared the combination of anti-leukotrienes and ICS to a higher-dose of ICS (step 3 versus step 3). No significant group difference was observed in this trial for participants with exacerbations requiring rescue oral corticosteroids over 16 weeks (N = 182 participants; RR 0.82, 95% CI 0.54 to 1.25), nor was there any significant difference in exacerbations requiring hospitalisation. There was no statistically significant group difference in withdrawals overall or because of any cause with either protocol. No trial explored the impact of adding anti-leukotrienes as a means to taper the dose of ICS. The addition of anti-leukotrienes to ICS is not associated with a statistically significant reduction in the need for rescue oral corticosteroids or hospital admission compared to the same or an increased dose of ICS in children and adolescents with mild to moderate asthma. Although anti-leukotrienes have been licensed for use in children for over 10 years, the paucity of paediatric trials, the absence of data on preschoolers, and the variability in the reporting of relevant clinical outcomes considerably limit firm conclusions. At present, there is no firm evidence to support the efficacy and safety of anti-leukotrienes as add-on therapy to ICS as a step-3 option in the therapeutic arsenal for children with uncontrolled asthma symptoms on low-dose ICS.

The evidence was updated until January 2013. We found five studies of children with asthma; of them, four studies, representing 559 children (aged six to 18 years) with mild to moderate asthma, contributed data to the review. No study enrolled pre-school children (i.e. aged under six years). Three studies compared the combination of anti-leukotrienes and ICS with the same dose of ICS alone; one study compared the combination of anti-leukotrienes and ICS to a higher dose of ICS; and no study tested whether the addition of anti-leukotriene to ICS could allow the tapering of the dose of ICS while maintaining asthma control. All studies used montelukast as the anti-leukotriene agent, which was administered for four to 16 weeks. Included studies enrolled both girls and boys and between 65% and 69% were boys. All trials enrolled children with mild to moderate airway obstruction. Whether comparing the addition of anti-leukotrienes to ICS to the same dose or an increased dose of ICS, there was no difference in the number of participants experiencing one or more moderate exacerbations (that is, requiring oral corticosteroids) or severe exacerbations (i.e. requiring a hospital admission). A single study comparing the same ICS dose reported lung function tests and showed no or small group differences depending on the test used. There is no firm evidence to support that adding montelukast to ICS is safe and effective to reduce the occurrence of moderate or severe asthma attacks in children taking low-dose ICS and whose symptoms remain uncontrolled. After being on the market for more than 10 years, the limited number of available studies testing antileukotrienes in children, the absence of data on preschoolers, and the inconsistency of available trials in reporting of efficacy and safety clinical outcomes is disappointing and limit the conclusions. This review is based on a small number of identified trials conducted in children with asthma; none were conducted in preschoolers. As a single study of moderate duration reported all measures of efficacy and most measures of safety, our confidence in the quality of evidence is low. Other important measures of asthma control were either not measured or reported in different formats, so they could not be pooled. In other words, there are too few paediatric trials to conclude firmly whether either treatment is superior to the other.

10.1002/14651858.CD009585.pub2

cochrane-simplification-train-3395

cochrane-simplification-train-3395

We included 26 studies with 526 participants. We assessed the studies as being at high or unclear risk of bias overall. We only included randomised controlled trials (RCTs), although the description of randomisation was incomplete in some included studies. We aimed to include double blind RCTs, but two studies were only single blinded. There was inconsistency in the reporting of outcome measures. We analysed the data using a fixed-effect model, and for some outcomes heterogeneity was high. There was a risk of imprecise results due to the low numbers of participants in the included studies. For these reasons we downgraded the quality of the evidence from high to either low or very low. For the primary outcome of breathlessness, the standardised mean post-treatment dyspnoea score was 0.32 points better in the opioid group compared to the placebo group (ranging from a 0.53 point reduction to a 0.10 point reduction) (12 RCTs, 338 participants, low quality evidence). The standardised mean change from baseline dyspnoea score was 0.11 points better in the opioids group compared to the placebo group (ranging from a 0.40 point reduction to a 0.19 increase) (six RCTs, 194 participants, very low quality evidence). A lower score indicates an improvement in breathlessness. The evidence for the six-minute walk test (6MWT) was conflicting. The total distance in 6MWT was 28 metres (m) better in the opioids group compared to placebo (ranging from 113 m to 58 m) (one RCT, 11 participants, very low quality evidence). However, the change in baseline was 48 m worse in the opioids group (ranging from 36 m to 60 m) (two RCTs, 26 participants, very low quality evidence). The adverse effects reported included drowsiness, nausea and vomiting, and constipation. In those studies, participants were 4.73 times more likely to experience nausea and vomiting compared to placebo, three times more likely to experience constipation, and 2.86 times more likely to experience drowsiness (nine studies, 162 participants, very low quality evidence). Only four studies assessed quality of life, and none demonstrated any significant change. There is some low quality evidence that shows benefit for the use of oral or parenteral opioids to palliate breathlessness, although the number of included participants was small. We found no evidence to support the use of nebulised opioids. Further research with larger numbers of participants, using standardised protocols and with quality of life measures included, is needed.

We searched for studies up to 19 October 2015, and we included 26 studies with 526 people. These people had breathlessness from different types of lung disease. Some were given opioid drugs and some were given other drugs or a placebo, and studies compared the reporting of breathlessness to see if there was any difference. Some studies also looked at the amount of time people could exercise to see if there were any differences. Some people came from home, and some came from the hospital setting. There was some low quality evidence that showed a benefit of using oral or injectable opioid drugs for the treatment of the symptoms of breathlessness. There was no evidence for opioids by nebuliser. Some people experienced drowsiness, nausea, and vomiting. More research is needed using more people, and looking at effects on quality of life. We rated the quality of the evidence using one of the following grades: very low, low, moderate, or high. Very low quality evidence means we are uncertain about the results. High quality evidence means we are very certain about the results. For this Cochrane review, we found that the evidence was of low to very low quality. We included randomised controlled trials which were blinded, which means that participants and those people that assessed the results did not know whether the participants had received the opioid drug or a placebo. However, the trials were of small size, and some studies did not give enough information to allow us to assess whether they were of good quality.

10.1002/14651858.CD011008.pub2

cochrane-simplification-train-3396

cochrane-simplification-train-3396

We identified two RCTs that fulfilled our inclusion criteria. The two trials tested different comparisons. One multi-institutional RCT included 130 participants and compared hyperfractionated radiotherapy (six-week course with twice a day treatment of 117 cGy per fraction to a total dose of 7020 cGy) with conventional radiotherapy (six-week course with once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy). The median time overall survival (OS) was 8.5 months in the conventional group and 8.0 months in the hyperfractionated group. We detected no clear evidence of effect on OS or event-free survival (EFS) in participants receiving hyperfractionated radiotherapy compared with conventional radiotherapy (OS: hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.75 to 1.53; EFS: HR 1.26, 95% CI 0.83 to 1.90). Radiological response (risk ratio (RR) 0.94, 95% CI 0.54 to 1.63) and various types of toxicities were similar in the two groups. There was no information on other outcomes. According to the GRADE approach, we judged the quality of evidence to be low (i.e. further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate) for OS and EFS, and very low (i.e. we are very uncertain about the estimate) for radiological response and toxicities. The second RCT included 71 participants and compared hypofractionated radiotherapy (39 Gy in 13 fractions over 2.6 weeks, 3 Gy per fraction) with conventional radiotherapy (54 Gy in 30 fractions over six weeks, 1.8 Gy per fraction). This trial reported a median OS of 7.8 months for the hypofractionated group and 9.5 months for the conventional group. It reported a progression-free survival (PFS) of 6.3 months for the hypofractionated group and 7.3 months for the conventional group. We found no clear evidence of effect on OS (HR 1.03, 95% CI 0.53 to 2.01) or PFS (HR 1.19, 95% CI 0.63 to 2.22) in participants receiving hypofractionated radiotherapy when compared with participants receiving conventional radiotherapy. The mainly observed adverse effect was local erythema and dry desquamation especially behind the auricles. There were some other toxicities, but there was no statistically significant difference between treatment groups. There was no information on other outcomes. We judged the quality of evidence to be moderate (i.e. further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate) for OS, and low for PFS and toxicities. It should be mentioned that the sample size in this RCT was small, which could lead to insufficient statistical power for a clinically relevant outcome. We could make no definitive conclusions from this review based on the currently available evidence. Further research is needed to establish the role of radiotherapy in the management of newly diagnosed diffuse brainstem glioma in children and young adults. Future RCTs should be conducted with adequate power and all relevant outcomes should be taken into consideration. Moreover, international multicentre collaboration is encouraged. Considering the potential advantage of hypofractionated radiotherapy to decrease the treatment burden and increase the quality of remaining life, we suggest that more attention should be paid to hypofractionated radiotherapy.

Through comprehensive search and screening of medical databases, we found two clinical studies that tested different treatments. One study, with 130 participants included, compared hyperfractionated radiotherapy (six-week course with treatment twice a day ) with conventional radiotherapy (six-week course with treatment once a day ). The second study, with 71 participants included, compared hypofractionated radiotherapy (three-week course with treatment once a day ) with conventional radiotherapy. For the comparison of hyperfractionated radiotherapy and conventional radiotherapy, there was no clear evidence of effect on OS, event-free survival (EFS; time from diagnosis, study entry, or treatment to disease progression, disease relapse, a second tumour, or death), radiological response (a reduction in tumour size of more than 50%), and toxicities (damage to the body due to radiotherapy). For the comparison of hypofractionated radiotherapy and conventional radiotherapy, there was no clear evidence of effect on OS, progression-free survival (PFS; time from diagnosis, study entry, or treatment to disease progression), and side effects. For the hyperfractionated radiotherapy, when compared with conventional therapy, the quality of evidence was low for OS and EFS, and very low for radiological response and toxicities. For the hypofractionated radiotherapy, when compared with conventional therapy, the quality of evidence was moderate for OS, and low for PFS and toxicities.

10.1002/14651858.CD010439.pub2

cochrane-simplification-train-3397

cochrane-simplification-train-3397

The four included studies involved 163 participants, mainly active young adult males. All had had a primary (first time) traumatic anterior shoulder dislocation. Methodological quality was variable. All participants of one trial returned to active military duty. Two trials respectively reported similar numbers with reduced sports participation or non return to previous activities. The other, an inadequately reported, trial found significantly fewer people in the surgical group failed to attain previous levels of sports activity. Pooled results from all four trials showed that subsequent instability, either redislocation or subluxation, was statistically significantly less frequent in the surgical group (risk ratio 0.25, 95% confidence interval 0.14 to 0.44). This result remained statistically significant (risk ratio 0.32, 95% confidence interval 0.17 to 0.59) for the three trials reported in full. Half (17/33) of the conservatively treated patients with shoulder instability in these three trials opted for subsequent surgery. Different, mainly patient rated, functional assessment measures for the shoulder were recorded in these trials. The results were more favourable, usually statistically significantly so, in those treated surgically. The only complication reported was a septic joint in a surgically treated patient. There was no information on shoulder pain, long-term complications or resource use. Limited evidence supports primary surgery for young adults, usually male, engaged in highly demanding physical activities who have sustained their first acute traumatic shoulder dislocation. There is no evidence available to determine which treatment is better for other patient groups. Sufficiently powered, good quality, well reported randomised trials are required that compare surgical treatment with conservative treatment for these injuries, including in people at lower risk of recurrence. Long-term surveillance of outcome, looking at shoulder disorders including osteoarthritis is also required.

This review included four trials that involved 163 participants who were mainly active young adult males. All had had a primary (first time) anterior shoulder dislocation as a result of injury. Methodological quality of the trials was variable. Three trials found similar numbers returning to previous activities such as active military duties and sports. The other trial found significantly fewer people in the surgical group failing to attain previous levels of sports activity. Pooled results from the three trials that were reported in full (124 participants) showed that subsequent instability, either redislocation or subluxation (partial dislocation), was significantly less frequent in the surgical group. Half (17/33) of the conservatively treated patients with shoulder instability in these three trials opted for subsequent surgery. Function, measured in different ways in the four trials, was usually better in those treated surgically. The only complication of treatment reported was an infected joint in a surgically treated patient. This review found that highly active young people were less likely to have an unstable shoulder when treated surgically after an acute anterior shoulder dislocation.

10.1002/14651858.CD004325.pub2

cochrane-simplification-train-3398

cochrane-simplification-train-3398

Three studies qualified for inclusion in this review (Khilnani 1991; Loisel 1996; Soupre 1998). There was a decrease in the ML-UVCs group in the number of additional PIVs used in the first week of life [WMD -1.42, (95% CI -1.74, -1.10), p<0.00001, number of infants (n) = 99]. There was no significant effect on the number of additional PIVs used in the first four weeks of life [MD -2.30, (95% CI -6.65, 2.05), n=36]. There was an increase in catheter malfunction in the ML-UVCs group [typical RR 3.69 (95% CI 0.99, 13.81), p=0.05; RD 0.15 (95% CI 0.03, 0.27), p=0.01; NNH was 7, 95% CI 4, 33; n=99]. The following outcomes were not significantly different in the two groups: clinical sepsis, catheter related blood stream infection, catheter-associated thrombosis, complications related to catheter malposition in heart and great vessels, NEC and early neonatal mortality. The use of ML-UVCs in comparison to SL-UVCs in neonates is associated with decrease in the usage of PIVs in first week of life, but an increase in catheter malfunctions. As the quality of included randomized studies is poor and the estimates of clinically important complications are imprecise, no firm recommendations can be made regarding the choice of UVC. Adequately powered, properly randomized and properly blinded controlled trials are needed that address the effectiveness and safety of ML-UVCs (double and triple lumen) in comparison to SL-UVCs. These studies should also address the impact of type of catheter material.

Three clinical trials involving/completed by 113 babies were identified that compared double-lumen catheters to single-lumen catheters. None of the studies used triple-lumen catheters. All three trials found that use of a double-lumen catheter lowered the number of additional venous placements needed during the first week of life. The double-lumen catheters, however, clogged, leaked, and broke more often. In these studies, no significant difference was found in catheter placement difficulty and misplacement, catheter-related infections or blood clots, other serious complications, or rate of infant mortality. But the quality of studies was poor, and sample sizes were too small to draw valid conclusions about many complication rates. Available clinical trials at present do not provide a basis for recommending one catheter type over another in this setting.

10.1002/14651858.CD004498.pub2

cochrane-simplification-train-3399

cochrane-simplification-train-3399

Thirteen trials involving 2914 women were included, of whom 2494 were included in the analysis. Oil-soluble contrast media (OSCM) versus no intervention The OSCM group had a higher rate of live birth (odds ratio (OR) 3.09, 95% CI 1.39 to 6.91, 1 RCT, 158 women, low quality evidence) and ongoing pregnancy (OR 3.59, 95% CI 2.06 to 6.26, 3 RCTs, 382 women, I2 = 0%, low quality evidence) than women who had no intervention. Our findings suggest that among subfertile women with a 17% chance of an ongoing pregnancy if they have no intervention, the rate will increase to between 29% and 55% if they have tubal flushing with OSCM. Water-soluble contrast media (WSCM) versus no intervention There was no evidence of a difference between the groups in rates of live birth (OR 1.13, 95% CI 0.67 to 1.91, 1 RCT, 334 women, very low quality evidence) or ongoing pregnancy (OR 1.14, 95% CI 0.71 to 1.84, 1 RCT, 334 women, very low quality evidence). OSCM versus WSCM Two RCTs reported live birth: one found a higher live birth rate in the oil-soluble group and the other found no evidence of a difference between the groups. These studies were not pooled due to very high heterogeneity (I2 = 93%). There was no evidence of a difference between the groups in rates of ongoing pregnancy, however there was high heterogeneity (OR 1.44, 95% CI 0.84 to 2.47, 5 RCTs, 1454 women, I2 = 76%, random-effects model, very low quality evidence). OSCM plus WSCM versus WSCM alone There was no evidence of a difference between the groups in rates of live birth (OR 1.06, 95% CI 0.64 to 1.77, 1 RCT, 393 women, very low quality evidence) or ongoing pregnancy (OR 1.23, 95% CI 0.87 to 1.72, 4 RCTs, 633 women, I2 = 0%, low quality evidence). There was no evidence of a difference between any of the interventions in rates of adverse events, but such events were poorly reported in most studies. The evidence suggests that tubal flushing with oil-soluble contrast media may increase the chance of pregnancy and live birth compared to no intervention. Findings for other comparisons were inconclusive due to inconsistency and lack of statistical power. There was insufficient evidence on adverse events to reach firm conclusions. Further robust randomised controlled trials are needed.

The evidence was current to June 2014. We included randomised controlled trials (RCTs) looking at the effect flushing of the fallopian tubes (with either oil-soluble or water-soluble contrast media) has on live birth and pregnancy rates in women with subfertility. Such women were those who had not been able to conceive after at least six months of unprotected sexual intercourse. We also looked at the rates of adverse events, including miscarriage and ectopic pregnancy (a pregnancy growing outside the womb) after flushing the tubes. We included 13 RCTs (2914 women). The trials compared oil-soluble and water-soluble media with no intervention and with each other. We found evidence that tubal flushing with oil-soluble media may increase the chances of live birth and ongoing pregnancy, compared to no intervention. Our findings suggest that among subfertile women with a 17% chance of ongoing pregnancy if they have no intervention, the rate will increase to between 29% and 55% if they have tubal flushing with oil-based contrast media. We found no evidence of a difference between water-soluble contrast media and no intervention and the contrast media compared one against the other with respect to live birth and pregnancy, though there were few data for most comparisons. There was no evidence of a difference between any of the groups with respect to adverse events, but such events were poorly reported in most studies. The overall quality of the evidence was low or very low for all comparisons. The main limitations were imprecision, risk of bias and inconsistency. There were too few studies to evaluate the risk of publication bias.

10.1002/14651858.CD003718.pub4