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cochrane-simplification-train-2300

cochrane-simplification-train-2300

We included a total of six trials (four randomized and two quasi-randomized) with 102 eyes in 61 children. Two trials were conducted in the USA and one trial each in Egypt, Israel, Lebanon and Saudi Arabia. All trials included children aged younger than one year when diagnosed with PCG, and followed them for periods ranging from six months to five years. No two trials compared the same pair of surgical interventions, so we did not perform any meta-analysis. One trial compared trabeculotomy versus goniotomy; a second trial compared combined trabeculectomy-trabeculotomy with mitomycin C versus trabeculectomy-trabeculotomy with mitomycin C and deep sclerectomy; a third trial compared combined trabeculotomy-trabeculectomy versus trabeculotomy; a fourth trial compared one goniotomy versus two goniotomies; a fifth trial compared trabeculotomy versus viscocanalostomy; and the sixth trial compared surgical goniotomy versus neodymium-YAG laser goniotomy. For IOP change and surgical success (defined by IOP achieved), none of the trials reported a difference between pairs of surgical techniques. However, due to the limited sample sizes for all trials (average of 10 children per trial), the evidence as to whether a particular surgical technique is effective and which surgical technique is better still remains uncertain. Adverse events, such as choroidal detachment, shallow anterior chamber and hyphema, were reported from four trials. None of the trials reported quality of life or economic data. These trials were neither designed nor reported well overall. Two trials were quasi-randomized trials and judged to have high risk of selection bias; four trials were at unclear or high risk for performance bias and detection bias; and we judged one trial to have high risk of attrition bias due to high proportions of losses to follow-up. Due to poor study design and reporting, the reliability and applicability of evidence remain unclear. No conclusions could be drawn from the trials included in this review due to paucity of data. More research is needed to determine which of the many surgeries performed for PCG are effective.

We found six trials comparing different surgeries for PCG. These trials included 102 eyes of 61 children. Two trials were conducted in the USA and one trial in each of these four countries: Egypt, Israel, Lebanon and Saudi Arabia. All trials enrolled infants younger than one year when diagnosed with PCG, and followed them from six months to five years after surgery. No two trials compared the same pair of surgical interventions. One trial compared trabeculotomy versus goniotomy; the second trial compared combined trabeculectomy-trabeculotomy with mitomycin C (CTTM) versus trabeculectomy-trabeculotomy with mitomycin C with deep sclerectomy (CTTM-DS); the third trial compared combined trabeculotomy-trabeculectomy versus trabeculotomy; the fourth trial compared one goniotomy versus two goniotomies; the fifth trial compared trabeculotomy versus viscocanalostomy; and the sixth trial compared goniotomy using a blade versus a laser. The evidence is current to 23 June 2014. In our review, no two trials compared the same pair of operations. Further, there were small numbers of children included in each trial (average of 10 children per trial), thus limiting our ability to draw conclusions about the effectiveness of one surgery over another. Four trials reported adverse events, but no trial reported an important difference between pairs of operations. None of the trials reported quality of life or economic data. The overall quality of the evidence on our review topic was poor. All trials had some limitations in study design, reporting, or both. None of the trials enrolled enough participants to detect an evident difference between surgeries.

10.1002/14651858.CD008213.pub2

cochrane-simplification-train-2301

cochrane-simplification-train-2301

We included six trials in the review, with a total of 429 adult participants, the majority of whom were male (63%). Three trials evaluated different types of fixation and three analysed different types of bone graft substitutes. All six trials were small and at substantial risk of bias. We judged the quality of most of the available evidence to be very low, meaning that we are very uncertain about these results. One trial compared the use of a circular fixator combined with insertion of percutaneous screws (hybrid fixation) versus standard open reduction and internal fixation (ORIF) in people with open or closed Schatzker types V or VI tibial plateau fractures. Results (66 participants) for quality of life scores using the 36-item Short Form Health Survey (SF-36)), Hospital for Special Surgery (HSS) scores and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function scores tended to favour hybrid fixation, but a benefit of ORIF could not be ruled out. Participants in the hybrid fixation group had a lower risk for an unplanned reoperation (351 per 1000 people compared with 450 in the ORIF group; 95% CI 197 fewer to 144 more) and were more likely to have returned to their pre-injury activity level (303 per 1000 people, compared with 121 in the ORIF group; 95% CI 15 fewer to 748 more). Results of the two groups were comparable for the WOMAC pain subscale and stiffness scores, but mean knee range of motion values were higher in the hybrid group. Another trial compared the use of a minimally invasive plate (LISS system) versus double-plating ORIF in 84 people who had open or closed bicondylar tibial plateau fractures. Nearly twice as many participants (22 versus 12) in the ORIF group had a bone graft. Quality of life, pain, knee range of motion and return to pre-injury activity were not reported. The trial provided no evidence of differences in HSS knee scores, complications or reoperation entailing implant removal or revision fixation. A quasi-randomised trial comparing arthroscopically-assisted percutaneous reduction and internal fixation versus standard ORIF reported results at 14 months in 58 people with closed Schatzker types II or III tibial plateau fracture. Quality of life, pain and return to pre-injury activity were not reported. There was very low quality evidence of higher HSS knee scores and higher knee range of motion values in the arthroscopically assisted group. No reoperations were reported. Three trials compared different types of bone substitute versus autologous bone graft (autograft) for managing bone defects. Quality of life, pain and return to pre-injury activity were not reported. Only one trial (25 participants) reported on lower limb function, finding good or excellent results in both groups for walking, climbing stairs, squatting and jumping at 12 months. The incidences of individual complications were similar between groups in all three trials. One trial found no cases of inflammatory response in the 20 participants receiving bone substitute, and two found no complications associated with the donor site in the autograft group (58 participants). However, all 38 participants in the autologous iliac bone graft group of one trial reported prolonged pain from the harvest site. Two trials reported similar range of motion results in the two groups, whereas the third trial favoured the bone substitute group. Currently, there is insufficient evidence to ascertain the best method of fixation or the best method of addressing bone defects during surgery. However, the evidence does not contradict approaches aiming to limit soft-tissue dissection and damage or to avoid autograft donor site complications through using bone substitutes. Further well-designed, larger randomised trials are warranted.

We found six small studies (involving 429 adults) of different fixation methods and bone fillers in September 2014. All six trials were small and at substantial risk of bias. We judged the quality of most of the available evidence to be very low, meaning that we are very uncertain about these results Three studies evaluated different methods of fixation. One study found that hybrid fixation is more likely to result in better quality of life and lower-limb function, fewer complications requiring repeat surgery, and more people returning to pre-injury activity levels than standard ORIF. However, the possibility of a better result from ORIF could not be ruled out. Another study compared a minimally invasive, single-plate technique with a traditional open technique using two plates. This study found very little difference between the two groups in knee function, complications or reoperations. The third study compared arthroscopic surgery (which uses a tiny camera to visualise the joint) and internal fixation versus ORIF. It reported better functional outcome and knee mobility in the arthroscopy group. There were no reoperations. Three studies compared different bone substitutes versus bone grafts for managing bone defects, but reported on only a few outcomes. One study found similar results in the two groups in the numbers of participants with good walking, stair climbing, squatting and jumping ability at one year. All three studies found similar numbers of specific complications in the two groups. One study found that all participants in the bone graft group had prolonged pain from the harvest site of the bone graft. Two studies reported similar range of motion results in the two groups, whereas the third study found better results in the bone substitute group at one year. Currently, there is insufficient evidence to ascertain the best surgical methods of fixation and bone defect treatment for tibial plateau fractures in adults. Well-conducted trials are still needed to inform clinical decision-making.

10.1002/14651858.CD009679.pub2

cochrane-simplification-train-2302

cochrane-simplification-train-2302

Four studies (involving 206 participants) met the inclusion criteria for this review. Three studies, involving 194 participants, assessed the effects of online interventions to target executive functioning (that is monitoring and changing behaviour, problem solving, planning, etc.). These studies, which were all conducted by the same research team, compared online interventions against a 'placebo' (participants were given internet resources on brain injury). The interventions were delivered in the family home with additional support or training, or both, from a psychologist or doctoral student. The fourth study investigated the use of a computer program to target memory in addition to components of executive functioning (that is attention, organisation, and problem solving). No information on the study setting was provided, however a speech-language pathologist, teacher, or occupational therapist accompanied participants. Two studies assessed adolescents and young adults with mild to severe traumatic brain injury (TBI), while the remaining two studies assessed children and adolescents with moderate to severe TBI. Risk of bias We assessed the risk of selection bias as low for three studies and unclear for one study. Allocation bias was high in two studies, unclear in one study, and low in one study. Only one study (n = 120) was able to conceal allocation from participants, therefore overall selection bias was assessed as high. One study took steps to conceal assessors from allocation (low risk of detection bias), while the other three did not do so (high risk of detection bias). Primary outcome 1: Executive functioning: Technology-based intervention versus placebo Results from meta-analysis of three studies (n = 194) comparing online interventions with a placebo for children and adolescents with TBI, favoured the intervention immediately post-treatment (standardised mean difference (SMD) -0.37, 95% confidence interval (CI) -0.66 to -0.09; P = 0.62; I2 = 0%). (As there is no 'gold standard' measure in the field, we have not translated the SMD back to any particular scale.) This result is thought to represent only a small to medium effect size (using Cohen’s rule of thumb, where 0.2 is a small effect, 0.5 a medium one, and 0.8 or above is a large effect); this is unlikely to have a clinically important effect on the participant. The fourth study (n = 12) reported differences between the intervention and control groups on problem solving (an important component of executive functioning). No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. The quality of evidence for this outcome according to GRADE was very low. This means future research is highly likely to change the estimate of effect. Primary outcome 2: Memory One small study (n = 12) reported a statistically significant difference in improvement in sentence recall between the intervention and control group following an eight-week remediation programme. No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. Secondary outcomes Two studies (n = 158) reported on anxiety/depression as measured by the Child Behavior Checklist (CBCL) and were included in a meta-analysis. We found no evidence of an effect with the intervention (mean difference -5.59, 95% CI -11.46 to 0.28; I2 = 53%). The GRADE quality of evidence for this outcome was very low, meaning future research is likely to change the estimate of effect. A single study sought to record adverse events and reported none. Two studies reported on use of the intervention (range 0 to 13 and 1 to 24 sessions). One study reported on social functioning/social competence and found no effect. The included studies reported no data for other secondary outcomes (that is quality of life and academic achievement). This review provides low-quality evidence for the use of technology-based interventions in the rehabilitation of executive functions and memory for children and adolescents with TBI. As all of the included studies contained relatively small numbers of participants (12 to 120), our findings should be interpreted with caution. The involvement of a clinician or therapist, rather than use of the technology, may have led to the success of these interventions. Future research should seek to replicate these findings with larger samples, in other regions, using ecologically valid outcome measures, and reduced clinician involvement.

We identified four studies (including 206 participants) that investigated the effectiveness of technology-based interventions to rehabilitate children and adolescents with traumatic brain injury. All four studies were conducted in North America, with three originating from the same research team. One study with 120 participants used an online Counselor-Assisted Problem Solving (CAPS) intervention to rehabilitate executive functioning in adolescents aged 12 to 17 years. One study with 35 participants used a Teen Online Problem-Solving intervention to target the executive functioning of adolescents aged 11 to 18 years. One study with 40 participants used an online Family Problem Solving intervention to target outcomes such as behaviour and aspects of executive functioning in children aged 5 to 16 years. One study with 12 participants used a computer program to target cognitive-communication skills including memory and aspects of executive functions in adolescents and young adults aged 12 to 21 years. All funding sources were in the USA or Canada. One study was funded by the Colorado Department of Human Services and two National Institutes of Health (NIH) awards. A second study was also funded by a NIH grant. One study was funded by a hospital charity in addition to the Easter Seal Research Institute and Apple Canada. The final study was supported by the Ohio Department of Safety. This review found evidence that interventions employing technological aids did improve executive functions in adolescents with traumatic brain injury (i.e. a brain injury resulting from a road traffic accident, fall, or blow to the head). However, this result was relatively modest and is unlikely to have a clinically important effect on the child. One study employed technology to improve memory in adolescents with TBI and showed an improvement for the intervention group. It was not possible to determine how effective this approach was as the study failed to include adequate statistical information. Two studies examined the secondary outcomes of anxiety and depression but did not show any effect between the intervention and control groups at 6 months follow-up. Only one study recorded adverse events, and reported that none occurred. Two studies reported on the amount of use the intervention received. One study reported improvements in social functioning/social competence for the intervention group. No data were reported which related to the review's other secondary outcomes. We found the quality of evidence for all outcomes to be low, which means future research is likely to change the estimate of effect. All four studies were small, and it was not always possible to conceal group allocation to participants. Three studies failed to conceal group allocation to those who measured the outcomes.

10.1002/14651858.CD011020.pub2

cochrane-simplification-train-2303

cochrane-simplification-train-2303

We identified one randomized controlled study recruiting 97 low birthweight infants that met the inclusion criteria. The study was conducted in the UK in 1987 and 1988. Randomized infants received ETT suctioning every six or 12 hours during the first three days of life. The quality of reporting was limited and we rated the trial at high risk of bias. Furthermore, the trial lacked adequate power. There were no statistically significant differences in any of reported outcomes: bronchopulmonary dysplasia (defined as oxygen at more than 30 days; risk ratio (RR) 0.49, 95% confidence interval (CI) 0.20 to 1.20); incidence of pneumothorax (RR 0.70, 95% CI 0.24 to 2.05); intraventricular hemorrhage (RR 1.12, 95% CI 0.44 to 2.85); neonatal death (RR 1.40, 95% CI 0.58 to 3.37); and time on ventilation (median time 39 hours in the 12-hourly group and 28 hours in the six-hourly group; RD not applicable for this outcome as mean and standard deviation were not reported). Tests for heterogeneity were not applicable as only one study was included. There was insufficient evidence to identify the ideal frequency of ETT suctioning in ventilated neonates. Future research should focus on the effects in the very preterm newborns, that is, the most vulnerable population as concerns the risk of both lung and brain damage. Assessment should include the cases of prolonged ventilation, when more abundant, dense secretions are common. Clinical trials might include comparisons between 'as-scheduled' versus 'as-needed' endotracheal suctioning, that is, based on specific indications, as well frequent versus less frequent suctioning schedules.

We searched medical databases for clinical studies comparing different strategies regarding the frequency of endotracheal tube suction in newborn babies on ventilators. We found only one study recruiting 97 newborns with bodyweights under 2.5 kg (these are called low birthweight infants). Suctioning was performed every six or 12 hours during the first three days of life. There were no important differences on the time the babies were on the ventilator, occurrence of pneumothorax (collapsed lung), need for ventilation or oxygen at more than 30 days, bleeding in the brain, and death in the first month of life. In addition, the study reported no side effects. We only identified one study, which was conducted in 1987 and 1988 and had several shortcomings. We cannot advise health professionals and parents about the optimal frequency of suctioning when newborns are ventilated.

10.1002/14651858.CD011493.pub2

cochrane-simplification-train-2304

cochrane-simplification-train-2304

We included four studies (188 participants). Two studies were double-blind RCTs, one was a non-randomised controlled trial, and one was an observational retrospective case-matched study. The age of participants ranged from 27 to 37.8 years. In three studies participants had quiescent IBD and in one study participants had active or quiescent IBD. Participants in one study had co-morbid anxiety or depression. One study used duloxetine (60 mg daily), one study used fluoxetine (20 mg daily), one study used tianeptine (36 mg daily), and one study used various antidepressants in clinical ranges. Three studies had placebo controls and one study had a no treatment control group. One RCT was rated as low risk of bias and the other was rated as high risk of bias (incomplete outcome data). The non-randomised controlled trial was rated as high risk of bias (random sequence generation, allocation concealment, blinding). The observational study was rated as high methodological quality, but is still considered to be at high risk of bias given its observational design. The effect of antidepressants on anxiety and depression is uncertain. At 12 weeks, the mean anxiety score in antidepressant participants was 6.11 + 3 compared to 8.5 + 3.45 in placebo participants (MD -2.39, 95% -4.30 to -0.48, 44 participants, low certainty evidence). At 12 months, the mean anxiety score in antidepressant participants was 3.8 + 2.5 compared to 4.2 + 4.9 in placebo participants (MD -0.40, 95% -3.47 to 2.67, 26 participants; low certainty evidence). At 12 weeks, the mean depression score in antidepressant participants was 7.47 + 2.42 compared to 10.5 + 3.57 in placebo participants (MD -3.03, 95% CI -4.83 to -1.23, 44 participants; low certainty evidence). At 12 months, the mean depression score in antidepressant participants was 2.9 + 2.8 compared to 3.1 + 3.4 in placebo participants (MD -0.20, 95% -2.62 to 2.22, 26 participants; low certainty evidence). The effect of antidepressants on AEs is uncertain. Fifty-seven per cent (8/14) of antidepressant participants group reported AEs versus 25% (3/12) of placebo participants (RR 2.29, 95% CI 0.78 to 6.73, low certainty evidence). Commonly reported AEs include nausea, headache, dizziness, drowsiness, sexual problems, insomnia, fatigue, low mood/anxiety, dry mouth, muscle spasms and hot flushes. None of the included studies reported any serious AEs. None of the included studies reported on pain. One study (44 participants) reported on QoL at 12 weeks and another study (26 participants) reported on QoL at 12 months. Physical, Psychological, Social and Environmental QoL were improved at 12 weeks compared to placebo (all low certainty evidence). There were no group differences in QoL at 12 months (all low certainty evidence). The effect of antidepressants on maintenance of clinical remission and endoscopic relapse is uncertain. At 12 months, 64% (9/14) of participants in the antidepressant group maintained clinical remission compared to 67% (8/12) of placebo participants (RR 0.96, 95% CI 0.55 to 1.69; low certainty evidence). At 12 months, none (0/30) of participants in the antidepressant group had endoscopic relapse compared to 10% (3/30) of placebo participants (RR 0.14, 95% CI 0.01 to 2.65; very low certainty evidence). The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the efficacy and safety of antidepressants in IBD can be drawn. Future studies should employ RCT designs, with a longer follow-up and develop solutions to address attrition. Inclusion of objective markers of disease activity is strongly recommended as is testing antidepressants from different classes, as at present it is unclear if any antidepressant (or class thereof) has differential efficacy.

The researchers searched the medical literature up to 23 August 2018. Four published studies, including a total of 188 people, examined antidepressant therapy in people with IBD. The age of participants ranged from 27 to 37.8 years. In three studies participants had IBD in remission and in one study participants had either active IBD or IBD in remission. Participants in one study had co-existing anxiety or depression. One study used duloxetine (60 mg daily), one study used fluoxetine (20 mg daily), one study used tianeptine (36 mg daily), and one study used various antidepressants. Three studies had a placebo (e.g. sugar pill) control group and one study had a no treatment control group. The analysis showed that the symptoms of anxiety and depression were improved in those who took antidepressants compared to placebo. Participants who received antidepressants experienced more side effects than those who received placebo. Side effects reported by those taking antidepressants included: nausea, headache, dizziness, drowsiness, sexual problems, insomnia, fatigue, low mood/anxiety, dry mouth, poor sleep, restless legs and hot flushes. Some aspects of quality of life were improved as was IBD activity in the antidepressant group. The overall quality of the studies included in this review was poor because the studies included small numbers of participants, and involved IBD populations which differed from each other on key characteristics. In addition, different types of antidepressants were assessed so the evidence for any one antidepressant was uncertain. Therefore, future studies are needed to confirm these observations. The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the benefits and harms of antidepressants in IBD can be drawn. More studies are needed to allow for firm conclusions regarding the benefits and harms of the use of antidepressants in people with IBD.

10.1002/14651858.CD012680.pub2

cochrane-simplification-train-2305

cochrane-simplification-train-2305

We included four trials involving 1365 participants. Three trials compared the intravenous GP IIb-IIIa inhibitor Abciximab with intravenous placebo (1215 participants) and one trial compared the intravenous GP IIb-IIIa inhibitor Tirofiban with intravenous aspirin (150 participants). Treatment with either of these GP IIb-IIIa inhibitors did not significantly reduce long-term death or dependency (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.77 to 1.22, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.52 to 1.92, for the comparison between Tirofiban and aspirin) and had no effect on deaths from all causes (OR 1.08, 95% CI 0.77 to 1.53, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.35 to 2.82, for the comparison between Tirofiban and aspirin). Abciximab was associated with a significant increase in symptomatic intracranial haemorrhage (OR 4.6, 95% CI 2.01 to 10.54) and with a non-significant increase in major extracranial haemorrhage (OR 1.81, 95% CI 0.96 to 3.41), whereas the only small trial comparing Tirofiban with aspirin showed no increased risk of bleeding complications with Tirofiban (OR 0.32, 95% CI 0.03 to 3.19, for symptomatic intracranial haemorrhage; OR 3.04, 95% CI 0.12 to 75.83, for major extracranial haemorrhages). There was no significant inconsistency across the studies. The available trial evidence showed that, for individuals with acute ischaemic stroke, GP IIb-IIIa inhibitors are associated with a significant risk of intracranial haemorrhage with no evidence of any reduction in death or disability in survivors. These data do not support their routine use in clinical practice. The conclusion is driven by trials of Abciximab, which contributed 89% of the total number of study participants considered.

We identified four trials with a total of 1365 participants in searches conducted up to June 2013: three trials compared the intravenous GP IIb-IIIa inhibitor Abciximab with intravenous placebo and one trial compared the intravenous GP IIb-IIIa inhibitor Tirofiban with intravenous aspirin. The results showed that GP IIb-IIIa inhibitors cause bleeding in the brain, and that this complication offset any benefits. Therefore, GP IIb-IIIa inhibitors should be avoided in people with acute ischaemic stroke. Overall, the studies were considered at low risk of bias.

10.1002/14651858.CD005208.pub3

cochrane-simplification-train-2306

cochrane-simplification-train-2306

Nine trials were used in the analysis (n = 1282 patients). These trials were found to be predominantly at low risk of bias. We did not find strong evidence of an effect of DSI on the total duration of ventilation. Pooled data from nine trials demonstrated a 13% reduction in the geometric mean, with relatively wide confidence intervals (CI) indicating imprecision (95% CI 26% reduction to 2% increase, moderate quality evidence). Similarly, we did not find strong evidence of an effect on ICU length of stay (-10%, 95% CI -20% to 3%, n = 9 trials, moderate quality evidence) or hospital length of stay (-6%, 95% CI -18% to 8%, n = 8 trials, moderate quality evidence). Heterogeneity for these three outcomes was moderate and statistically significant. The risk ratio for ICU mortality was 0.96 (95% CI 0.77 to 1.21, n = 7 trials, moderate quality evidence), for rate of accidental endotracheal tube removal 1.07 (95% CI 0.55 to 2.12, n = 6 trials, moderate quality evidence), for catheter removal 1.48 (95% CI 0.76 to 2.90, n = 4 trials), and for incidence of new onset delirium 1.02 (95% CI 0.91 to 1.13, n = 3 trials, moderate quality evidence). Differences in the doses of any drug used or quality of life score (Short Form (SF)-36) did not reach statistical significance. Tracheostomy was performed less frequently in the DSI group (RR 0.73, 95% CI 0.57 to 0.92, n = 6 trials, moderate quality evidence). Sensitivity analysis of unlogged data resulted in similar findings. Post hoc analysis to further explain heterogeneity, based on study country of origin, showed that studies conducted in North America resulted in a reduction in the duration of mechanical ventilation (-21%, 95% CI -33% to -5%, n = 5 trials). We have not found strong evidence that DSI alters the duration of mechanical ventilation, mortality, length of ICU or hospital stay, adverse event rates, drug consumption, or quality of life for critically ill adults receiving mechanical ventilation compared to sedation strategies that do not include DSI. We advise that caution should be applied when interpreting and applying the findings as the overall effect of treatment is always < 1 and the upper limit of the CI is only marginally higher than the no-effect line. These results should be considered unstable rather than negative for DSI given the statistical and clinical heterogeneity identified in the included trials.

we included nine studies involving 1282 critically ill patients receiving mechanical ventilation. Studies compared daily sedation interruption to strategies that did not include an interruption. Studies were conducted worldwide and involved both medical and surgical critically ill patients. we did not find strong evidence that daily sedation interruption reduced the duration of mechanical ventilation, length of stay in the intensive care unit (ICU) or hospital, death, or the amount of drug used. The effect on adverse events such as accidental removal of the breathing tube or invasive devices, or the rate of delirium was uncertain. However, tracheostomy was performed less often in those who were managed with daily sedation interruption. Sedation practices are known to vary worldwide, and as such an analysis of studies conducted in North America showed a reduction in time on the breathing machine for those who were managed with daily sedation interruption compared to those who were not. we advise caution should be applied when interpreting and applying our study findings. The results are based upon a small number of studies that were heterogeneous or not uniform in terms of methods, patients studied, and clinical management and our overall results only marginally crossed the no-effect line.

10.1002/14651858.CD009176.pub2

cochrane-simplification-train-2307

cochrane-simplification-train-2307

We included two RCTs with 81 participants. One RCT involved 14 critically ill children with ARDS (very low quality of evidence), and one RCT involved 67 critically ill adults (very low quality evidence). Only one RCT (paediatric trial) provided data on mortality and found no difference between intervention and control. However, this trial was eligible for meta-analysis due to a cross-over design. We assessed the benefits and harms of aerosolized prostacyclin. One RCT found no difference in improvement of partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio (mean difference (MD) -25.35, 95% confidence interval (CI) -60.48 to 9.78; P = 0.16; 67 participants, very low quality evidence). There were no adverse events such as bleeding or organ dysfunction in any of the included trials. Due to the limited number of RCTs, we were unable to perform the prespecified subgroup and sensitivity analyses or trial sequential analysis. We are unable to tell from our results whether the intervention has an important effect on mortality because the results were too imprecise to rule out a small or no effect. Therefore, no current evidence supports or refutes the routine use of aerosolized prostacyclin for people with ARDS. There is an urgent need for more RCTs.

This review was updated in 2017. We included two randomized controlled trials (RCT; clinical studies where people are randomly put into one of two or more treatment groups), one involving 14 critically ill children with ARDS and one involving 67 critically ill adults with ARDS. The trials did not measure severity of illness, resolution of organ dysfunction, length of stay in intensive care unit or hospital, and quality of life. The study authors did not report side effects such as bleeding, organ dysfunction, airway reactivity or side effects unrelated to the intervention. None of the included trials reported receiving money from drug companies. Only the RCT involving children provided data on deaths, with no clear difference with and without prostacyclin. The RCT in adults reported a trend towards improved blood oxygen levels, for participants who were treated with alprostadil (prostaglandin E1). Therefore, we could not identify a clear advantage of the use of aerosolized prostacyclin in critically ill children or adults with low blood oxygen levels. The quality of the evidence was very low because of the limited number of participants and poor trial design. The RCT involving children used a cross-over design where one group received aerosolized prostacyclin first and the other group received saline (salt solution). They then changed over to the alternate treatment. There was insufficient information on the effect on death in both trials. We conclude that there is a need for a large-scale clinical trial with low risk of misleading information to investigate the advantages and harms of prostacyclin for critically ill people.

10.1002/14651858.CD007733.pub3

cochrane-simplification-train-2308

cochrane-simplification-train-2308

We included 11 trials reporting results for 3403 women evaluating the effects of vaginal cleansing (eight using povidone-iodine, two chlorhexidine, one benzalkonium chloride) on post-cesarean infectious morbidity. Additionally, some trials used vaginal preparations using sponge sticks, douches, or soaked gauze wipes. The control groups were typically no vaginal preparation (eight trials) or the use of a saline vaginal preparation (three trials). The risk of bias in the studies reduced our confidence in the results for endometritis outcomes. Vaginal preparation with antiseptic solution immediately before cesarean delivery probably reduces the incidence of post-cesarean endometritis from 8.7% in control groups to 3.8% in vaginal cleansing groups (average risk ratio (RR) 0.36, 95% confidence interval (CI) 0.20 to 0.63, 10 trials, 3283 women, moderate quality of evidence). Subgroup analysis could not rule out larger reductions in endometritis with antiseptics in women who were in labor or in women whose membranes had ruptured when antiseptics were used. Risks of postoperative fever and postoperative wound infection may be slightly lowered by antiseptic preparation, but the confidence intervals around the effects for both outcomes are consistent with a large reduction in risk and no difference between groups (fever: RR 0.87 (0.72 to 1.05; wound infection: RR 0.74 (95% CI 0.49 to 1.11), both moderate-quality evidence). Two trials reported a lower risk of a composite outcome of wound complication or endometritis in women receiving preoperative vaginal preparation (RR 0.46, 95% CI 0.26 to 0.82, two trials, 499 women, moderate-quality evidence). No adverse effects were reported with either the povidone-iodine or chlorhexidine vaginal cleansing. Vaginal preparation with povidone-iodine or chlorhexidine solution compared to saline or not cleansing immediately before cesarean delivery probably reduces the risk of post-cesarean endometritis. Subgroup analysis could not rule out larger reductions in endometritis with antiseptics in women who were in labor or in women whose membranes had ruptured when antiseptics were used. The quality of the evidence using GRADE was moderate for all reported outcomes. We downgraded the outcome of post-cesarean endometritis and composite of wound complications or endometritis for risk of bias and postoperative fever and postoperative wound infections for wide CIs. As a simple, generally inexpensive intervention, providers may consider implementing preoperative vaginal cleansing with povidone-iodine or chlorhexidine before performing cesarean deliveries.

We searched for evidence on July 10, 2017. In this update, we have included 11 randomized controlled studies, involving a total of 3403 women undergoing cesarean section. Eight studies used povidone-iodine for vaginal cleansing, two chlorhexidine, and one benzalkonium chloride. The quality of the evidence using GRADE was moderate for the reported outcomes. We found that cleansing the vagina with an antiseptic solution compared to not cleansing or using saline or water immediately before the cesarean delivery more than halved the risk of post-cesarean infection of the uterus from a rate of 8.7% down to a rate of 3.8% (10 studies, 3283 women). While we should be cautious about results found for women in certain groups, we did also find that the benefit was also seen if the woman's waters had already broken (from 17.9% to 4.3% with vaginal cleansing; three studies, 272 women) and if women were already in labor at the time of the cesarean delivery (from a rate of 11.1% down to 4.7% with vaginal cleansing; four studies, 960 women women). The benefits were similar using both povidone-iodine and chlorhexidine. The risk of experiencing a fever (eight studies, 3109 women) or wound infection (eight studies, 2839 women) after the cesarean delivery may be slightly lowered by antiseptic preparation, but the results were not entirely clear. Only the composite outcome of wound complication or endometritis was reduced overall for women receiving preoperative vaginal cleansing (two studies, 499 women). None of the reports mentioned that any women had adverse events such as an allergic reaction to the cleansing solution or irritation. Cleansing the vagina immediately before a cesarean delivery with either an iodine-based or chlorhexidine-based solution probably reduces the risk of infection of the uterus after a cesarean section. This benefit may be greater for women who have their cesarean delivery after their membranes have already ruptured or they are already in labor. This is a generally simple, well-tolerated way to lower the chances of developing an infection after having a baby by cesarean.

10.1002/14651858.CD007892.pub6

cochrane-simplification-train-2309

cochrane-simplification-train-2309

Thirty-two randomized controlled trials meeting the inclusion criteria were identified. Many had significant methodological flaws. Change in neurological function, our primary outcome measure, was assessed in 29 trials, but sufficient data for meta-analysis were only available in 13 studies, involving 879 treated participants and 909 controls. There was no overall significant difference between the treated and control groups (SMD -0.25, 95% CI -0.56 to 0.05), although one subgroup analysis (four trials using tolrestat) favored treatment. A benefit for neuropathic symptoms was suggested by a group of trials using a dichotomized endpoint (improvement or not), but this was contradicted by another group of trials which measured symptoms on a continuous scale. There was no overall benefit on nerve conduction parameters (27 studies) or foot ulceration (one study). Quality of life was not assessed in any of the studies. While most adverse events were infrequent and minor, three compounds had dose limiting adverse events that lead to their withdrawal from human use: severe hypersensitivity reactions with sorbinil, elevation of creatinine with zenarestat, and alteration of liver function with tolrestat. We found no statistically significant difference between aldose reductase inhibitors and placebo in the treatment of diabetic polyneuropathy. Any future clinical trials of aldose reductase inhibitors should be restricted to compounds proven to have substantial biological or preclinical advantages over previously tested agents.

The authors reviewed the results of all randomized trials that compared an aldose reductase inhibitor with a control and lasted at least six months. Many of the 32 randomized controlled trials identified had significant methodological flaws. The trials used a variety of measures to look for a benefit of treatment with aldose reductase inhibitors. The authors elected to focus primarily on changes in muscle strength and sensation. These were chosen because they are thought be the best indicator of the severity of polyneuropathy, and they have been used in a previous landmark study of the effects of intensive blood sugar control on diabetic neuropathy, as well as in studies of treatments in other types of polyneuropathy. Muscle strength or sensation were assessed in 29 trials, but sufficient data for analysis was only available in 13 studies, involving 879 treated participants and 906 controls. There was no overall significant difference between the treated and control groups. For one drug, tolrestat, there was possibly some benefit, but concerns about liver toxicity have lead to withdrawal of tolrestat from use in humans. A few trials did report that symptoms of neuropathy improved for the treated group, but this was contradicted by most other trials. No benefit was detected on electromyography (EMG) parameters (27 studies) or foot ulceration (one study). Quality of life was not assessed in any of the studies. Adverse effects were infrequent and were mostly minor, except for severe allergic reactions with sorbinil, impaired kidney function with zenarestat, and alteration of liver function with tolrestat. The authors concluded that there was no significant benefit of treatment with aldose reductase inhibitors for diabetic polyneuropathy.

10.1002/14651858.CD004572.pub2

cochrane-simplification-train-2310

cochrane-simplification-train-2310

We included six studies treating 310 participants (mean or median age 49 to 64 years) with various neuropathic pain conditions. Five studies used a cross-over design, and one used a parallel-group design; 272 participants were randomised to treatment with nortriptyline, 145 to placebo, 94 to gabapentin, 56 to gabapentin plus nortriptyline, 55 to morphine, 55 to morphine plus nortriptyline, 39 to chlorimipramine, and 33 to amitriptyline. Treatment periods lasted from three to eight weeks. All studies had one or more sources of potential major bias. No study provided first or second tier evidence for any outcome. Only one study reported our primary outcome of people with at least 50% reduction in pain. There was no indication that either nortriptyline or gabapentin was more effective in postherpetic neuralgia (very low quality evidence). Two studies reported the number of people with at least moderate pain relief, and one reported the number who were satisfied with their pain relief and had tolerable adverse effects. We considered these outcomes to be equivalent to our other primary outcome of Patient Global Impression of Change (PGIC) much or very much improved. We could not pool data, but third tier evidence in individual studies indicated similar efficacy to other active interventions (gabapentin, morphine, chlorimipramine, and amitriptyline), and to placebo in the conditions studied (very low quality evidence). Adverse event reporting was inconsistent and fragmented. More participants reported adverse events with nortriptyline than with placebo, similar numbers with nortriptyline and other antidepressants (amitriptyline and chlorimipramine) and gabapentin, and slightly more with morphine (very low quality evidence). No study reported any serious adverse events or deaths. We found little evidence to support the use of nortriptyline to treat the neuropathic pain conditions included in this review. There were no studies in the treatment of trigeminal neuralgia. The studies were methodologically flawed, largely due to small size, and potentially subject to major bias. The results of this review do not support the use of nortriptyline as a first line treatment. Effective medicines with much greater supportive evidence are available, such as duloxetine and pregabalin.

In January 2015, we performed searches to look for clinical trials where nortriptyline was used to treat neuropathic pain in adults. We found six studies, with 310 participants with various neuropathic pain conditions. Studies were randomised and double-blind, but often with small numbers of participants. It was not possible to combine information from the different studies, but individually most studies indicated equivalent benefit from nortriptyline (usually at a dose between 50 mg and 100 mg daily) when compared with amitriptyline or chlorimipramine (other antidepressants), gabapentin (an antiepileptic), morphine (an opioid), or placebo (very low quality evidence). More people experienced adverse events with nortriptyline than with placebo, but numbers were similar for nortriptyline and other active medicines (very low quality evidence). There was too little information of adequate quality to be sure that nortriptyline works as a pain medicine in the type of neuropathic pain studies in this review. Other medicines have been shown to be effective.

10.1002/14651858.CD011209.pub2

cochrane-simplification-train-2311

cochrane-simplification-train-2311

We have included in this review 41 studies (27,951 participants) in adults and adolescents, along with eight studies (8453 participants) in children. We judged that the overall risk of bias was low for all-cause events, and we obtained data on SAEs from all study authors. All except 542 adults (and none of the children) were given salmeterol and fluticasone in the same (combination) inhaler. Deaths Eleven of a total of 14,233 adults taking regular salmeterol and ICS died, as did 13 of 13,718 taking regular ICS at the same dose. The pooled Peto odds ratio (OR) was 0.80 (95% confidence interval (CI) 0.36 to 1.78; participants = 27,951; studies = 41; I² = 0%; moderate-certainty evidence). In other words, for every 1000 adults treated for 25 weeks, one death occurred among those on ICS alone, and the corresponding risk among those taking salmeterol and ICS was also one death (95% CI 0 to 2 deaths). No children died, and no adults or children died of asthma, so we remain uncertain about mortality in children and about asthma mortality in any age group. Non-fatal serious adverse events A total of 332 adults receiving regular salmeterol with ICS experienced a non-fatal SAE of any cause, compared to 282 adults receiving regular ICS. The pooled Peto OR was 1.14 (95% CI 0.97 to 1.33; participants = 27,951; studies = 41; I² = 0%; moderate-certainty evidence). For every 1000 adults treated for 25 weeks, 21 adults on ICS alone had an SAE, and the corresponding risk for those on salmeterol and ICS was 23 adults (95% CI 20 to 27). Sixty-five of 4229 children given regular salmeterol with ICS suffered an SAE of any cause, compared to 62 of 4224 children given regular ICS. The pooled Peto OR was 1.04 (95% CI 0.73 to 1.48; participants = 8453; studies = 8; I² = 0%; moderate-certainty evidence). For every 1000 children treated for 23 weeks, 15 children on ICS alone had an SAE, and the corresponding risk for those on salmeterol and ICS was 15 children (95% CI 11 to 22). Asthma-related serious adverse events Eighty and 67 adults in each group, respectively, experienced an asthma-related non-fatal SAE. The pooled Peto OR was 1.15 (95% CI 0.83 to 1.59; participants = 27,951; studies = 41; I² = 0%; low-certainty evidence). For every 1000 adults treated for 25 weeks, five receiving ICS alone had an asthma-related SAE, and the corresponding risk among those on salmeterol and ICS was six adults (95% CI 4 to 8). Twenty-nine children taking salmeterol and ICS and 23 children taking ICS alone reported asthma-related events. The pooled Peto OR was 1.25 (95% CI 0.72 to 2.16; participants = 8453; studies = 8; I² = 0%; moderate-certainty evidence). For every 1000 children treated for 23 weeks, five receiving an ICS alone had an asthma-related SAE, and the corresponding risk among those receiving salmeterol and ICS was seven children (95% CI 4 to 12). We did not find a difference in the risk of death or serious adverse events in either adults or children. However, trial authors reported no asthma deaths among 27,951 adults or 8453 children randomised to regular salmeterol and ICS or ICS alone over an average of six months. Therefore, the risk of dying from asthma on either treatment was very low, but we remain uncertain about whether the risk of dying from asthma is altered by adding salmeterol to ICS. Inclusion of new trials has increased the precision of the estimates for non-fatal SAEs of any cause. We can now say that the worst-case estimate is that at least 152 adults and 139 children must be treated with combination salmeterol and ICS for six months for one additional person to be admitted to the hospital (compared to treatment with ICS alone). These possible risks still have to be weighed against the benefits experienced by people who take combination treatment. However more than 90% of prescribed treatment was taken in the new trials, so the effects observed may be different from those seen with salmeterol in combination with ICS in daily practice.

In total, we have included 41 studies in 27,951 adults and eight studies in 8453 children. Almost all studies used a combination inhaler to deliver salmeterol with ICS and compared this with the same dose of ICS for an average of six months. We did not find a difference in the risk of death or serious adverse events in either adults or children. Eleven of a total of 14,233 adults taking regular salmeterol and ICS died, as did 13 of 13,718 adults taking regular ICS at the same dose. For every 1000 adults treated for 25 weeks, researchers reported one death on ICS alone and a corresponding risk on salmeterol and ICS of one death (95% confidence Interval (CI) 0 to 2 deaths). No deaths in any studies were attributed to asthma, and researchers reported no deaths at all among children. A non-fatal serious adverse event of any cause occurred in 332 adults on regular salmeterol with ICS compared to 282 adults on regular ICS alone. For every 1000 adults treated for 25 weeks, 21 serious adverse events occurred on ICS alone, and the corresponding risk on salmeterol and ICS was 23 adults (95% CI 20 to 27). A total of 65 of 4229 children on regular salmeterol with ICS suffered a serious adverse event of any cause compared to 62 of 4224 children on regular ICS alone. For every 1000 children treated for 23 weeks, 15 serious adverse events occurred on ICS alone, and the corresponding risk on salmeterol and ICS was also 15 children (95% CI 11 to 22). Reviewers assessed the overall risk of bias for all-cause events as low. The two new large studies performed independent assessment to identify the cause of asthma-related serious adverse events. This makes current data on asthma events more reliable than previously reported. Trials reported no asthma deaths among 27,951 adults or 8453 children randomised to regular salmeterol and ICS or ICS alone over an average of six months. The risk of dying from asthma while receiving either treatment was therefore very low, but we remain uncertain about whether the risk of dying from asthma is altered by adding salmeterol to ICS. We can now say that the worst-case estimate (safety margin) from this review is that at least 152 adults and 139 children must be treated with combination salmeterol and ICS for six months for one additional person to be admitted to the hospital (compared to ICS alone). These possible risks must be weighed against the benefits experienced by people who take combination treatment. People monitored in the new trials took over 90% of their prescribed treatment. This is much more than the average amount of medication that people take outside a trial. Therefore the effects shown in trials may be different from the effects experienced by people at home who are not taking their inhalers as prescribed. Because very few people die of asthma, trials would have to be very large to detect differences in the death rate. Therefore it is probably not feasible to find out if adding salmeterol to ICS causes more deaths among participants in randomised controlled trials - as these trials would be very large, difficult to run, and expensive. It might be better to use case-control studies or to review asthma deaths (e.g. from medical records).

10.1002/14651858.CD006922.pub4

cochrane-simplification-train-2312

cochrane-simplification-train-2312

We included a total of four studies with 296 participants. Three studies with 206 participants compared quetiapine, an atypical (second-generation) antipsychotic, with placebo. One study used a cross-over design and two studies a parallel-group design. Study duration was eight or 12 weeks. Quetiapine was used in all studies with a bedtime dosage between 50 and 300 mg/day. All studies had one or more sources of potential major bias and we judged them to be at moderate risk of bias overall. The primary outcomes in this review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety). Second tier evidence indicated that quetiapine was not statistically superior to placebo in the number of participants with a 50% or more pain reduction (very low quality evidence). No study reported data on PGIC. A greater proportion of participants on quetiapine reported a 30% or more pain reduction (risk difference (RD) 0.12, 95% confidence interval (CI) 0.00 to 0.23; number needed to treat for an additional benefit (NNTB) 8, 95% CI 5 to 100) (very low quality evidence). A greater proportion of participants on quetiapine reported a clinically relevant improvement of health-related quality of life compared to placebo ( RD 0.18, 95% CI 0.05 to 0.31; NNTB 5, 95% CI 3 to 20) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing sleep problems (standardised mean difference (SMD) -0.67, 95% CI -1.10 to -0.23), depression (SMD -0.39, 95% CI -0.74 to -0.04) and anxiety (SMD -0.40, 95% CI -0.69 to -0.11) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing the risk of withdrawing from the study due to a lack of efficacy (RD -0.14, 95% CI -0.23 to -0.05) (very low quality evidence). There was no statistically significant difference between quetiapine and placebo in the proportion of participants withdrawing due to adverse events (tolerability) (very low quality evidence), in the frequency of serious adverse events (safety) (very low quality evidence) and in the proportion of participants reporting dizziness and somnolence as an adverse event (very low quality evidence). In more participants in the quetiapine group a substantial weight gain was noted (RD 0.08, 95% CI 0.02 to 0.15; number needed to treat for an additional harm (NNTH) 12, 95% CI 6 to 50) (very low quality evidence). We downgraded the quality of evidence by three levels to a very low quality rating because of limitations of study design, indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed). One parallel design study with 90 participants compared quetiapine (50 to 300 mg/day flexible at bedtime) to amitriptyline (10 to 75 mg/day flexible at bedtime). The study had three major risks of bias and we judged it to be at moderate risk of bias overall. We downgraded the quality of evidence by two levels to a low quality rating because of indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed). Third tier evidence indicated no statistically significant differences between the two drugs. Both drugs did not statistically significantly differ in the reduction of average scores for pain, fatigue, sleep problems, depression, anxiety and for limitations of health-related quality of life and in the proportion of participants reporting dizziness, somnolence and weight gain as a side effect (low quality evidence). Compared to amitriptyline, more participants left the study due to adverse events (low quality evidence). No serious adverse events were reported (low quality evidence). We found no relevant study with other antipsychotics than quetiapine in fibromyalgia. Very low quality evidence suggests that quetiapine may be considered for a time-limited trial (4 to 12 weeks) to reduce pain, sleep problems, depression and anxiety in fibromyalgia patients with major depression. Potential side effects such as weight gain should be balanced against the potential benefits in shared decision making with the patient.

In May 2016, we searched for clinical trials in which antipsychotics were used to treat symptoms of fibromyalgia in adults. We found a total of four studies with 298 participants. We found three studies with 208 participants, which were eight and 12 weeks long and compared quetiapine, an antipsychotic, against a fake medication (placebo). One hundred and sixty-six participants were diagnosed with major depression. We also found one study comprising 90 patients that compared quetiapine to an antidepressant named amitriptyline, which is frequently used in the treatment of fibromyalgia. Five people in this study were diagnosed with major depression. Quetiapine was not better than a fake medication in achieving a pain reduction of 50% or more (very low quality evidence). Quetiapine was better than the fake medication in achieving a pain reduction of 30% or more, reducing sleep problems, and improving depressed mood and anxiety (very low quality evidence). Quetiapine was better than the fake medication in improving health-related quality of life. Fewer participants dropped out of the trial due to lack of efficacy with quetiapine than with fake medication (very low quality evidence). There was no difference in tolerability and safety between quetiapine and a fake medication (very low quality evidence). For some people, quetiapine led to substantial weight gain and somnolence (sleepiness). Quetiapine and amitriptyline (an antidepressant which is frequently used to improve sleep and reduce pain in people with fibromyalgia) did not differ in the reduction of average scores for pain, fatigue, sleep problems, depression, anxiety and for limitations of health-related quality of life. Both drugs did not differ in the proportion of patients reporting dizziness, somnolence and weight gain as a side effect (low quality evidence). Compared with amitriptyline, more people experienced side effects and left the study due to side effects with quetiapine (low quality evidence). No serious side effects with either drug were reported (low quality evidence). We found no relevant study with other antipsychotics than quetiapine in fibromyalgia.

10.1002/14651858.CD011804.pub2

cochrane-simplification-train-2313

cochrane-simplification-train-2313

We included 85 trials involving a total of 8815 randomised participants (26 new studies were included in this update). There was a wide range of different treatments and a variety of trial designs. Many of the studies were judged to be at high risk of bias in one or more areas of trial design. Trials of salicylic acid (SA) versus placebo showed that the former significantly increased the chance of clearance of warts at all sites (RR (risk ratio) 1.56, 95% CI (confidence interval) 1.20 to 2.03). Subgroup analysis for different sites, hands (RR 2.67, 95% CI 1.43 to 5.01) and feet (RR 1.29, 95% CI 1.07 to 1.55), suggested it might be more effective for hands than feet. A meta-analysis of cryotherapy versus placebo for warts at all sites favoured neither intervention nor control (RR 1.45, 95% CI 0.65 to 3.23). Subgroup analysis for different sites, hands (RR 2.63, 95% CI 0.43 to 15.94) and feet (RR 0.90, 95% CI 0.26 to 3.07), again suggested better outcomes for hands than feet. One trial showed cryotherapy to be better than both placebo and SA, but only for hand warts. There was no significant difference in cure rates between cryotherapy at 2-, 3-, and 4-weekly intervals. Aggressive cryotherapy appeared more effective than gentle cryotherapy (RR 1.90, 95% CI 1.15 to 3.15), but with increased adverse effects. Meta-analysis did not demonstrate a significant difference in effectiveness between cryotherapy and SA at all sites (RR 1.23, 95% CI 0.88 to 1.71) or in subgroup analyses for hands and feet. Two trials with 328 participants showed that SA and cryotherapy combined appeared more effective than SA alone (RR 1.24, 95% CI 1.07 to 1.43). The benefit of intralesional bleomycin remains uncertain as the evidence was inconsistent. The most informative trial with 31 participants showed no significant difference in cure rate between bleomycin and saline injections (RR 1.28, 95% CI 0.92 to 1.78). Dinitrochlorobenzene was more than twice as effective as placebo in 2 trials with 80 participants (RR 2.12, 95% CI 1.38 to 3.26). Two trials of clear duct tape with 193 participants demonstrated no advantage over placebo (RR 1.43, 95% CI 0.51 to 4.05). We could not combine data from trials of the following treatments: intralesional 5-fluorouracil, topical zinc, silver nitrate (which demonstrated possible beneficial effects), topical 5-fluorouracil, pulsed dye laser, photodynamic therapy, 80% phenol, 5% imiquimod cream, intralesional antigen, and topical alpha-lactalbumin-oleic acid (which showed no advantage over placebo). We did not identify any RCTs that evaluated surgery (curettage, excision), formaldehyde, podophyllotoxin, cantharidin, diphencyprone, or squaric acid dibutylester. Data from two new trials comparing SA and cryotherapy have allowed a better appraisal of their effectiveness. The evidence remains more consistent for SA, but only shows a modest therapeutic effect. Overall, trials comparing cryotherapy with placebo showed no significant difference in effectiveness, but the same was also true for trials comparing cryotherapy with SA. Only one trial showed cryotherapy to be better than both SA and placebo, and this was only for hand warts. Adverse effects, such as pain, blistering, and scarring, were not consistently reported but are probably more common with cryotherapy. None of the other reviewed treatments appeared safer or more effective than SA and cryotherapy. Two trials of clear duct tape demonstrated no advantage over placebo. Dinitrochlorobenzene (and possibly other similar contact sensitisers) may be useful for the treatment of refractory warts.

Cryotherapy, usually using liquid nitrogen, is often used for the treatment of warts, but it is less convenient, more painful, and also more expensive. One study suggested that there is evidence that cryotherapy is better than SA for warts on the hands, but when we combined this study with our other results, we were unable to confirm this. We found that more aggressive cryotherapy appears to be more effective than gentle cryotherapy, but with an increased risk of adverse effects, such as pain, blistering, and scarring. We only looked at information from clinical trials of cryotherapy and not over-the-counter freezing treatments for warts, so we cannot say if these are as effective. During the production of the last version of this review, duct tape had gained favour as it is a safe and simple treatment that is easy to apply; however, the trial on which this was based was relatively small. In this updated review, we found two further trials of duct tape that suggested that this treatment is not as effective as first thought. Other treatments covered by this review include 5-fluorouracil, dinitrochlorobenzene, intralesional bleomycin, intralesional interferon, photodynamic therapy, and intralesional antigen. None of these treatments are used commonly, even by skin specialists, and there is much less evidence for their effectiveness. The limited available evidence we do have suggests that some of these treatments may be effective and could therefore be used for warts that have not responded to simpler, safer treatments, such as salicylic acid or cryotherapy. Overall, providing a useful idea of 'what works' from such a wide range of studies was difficult as many studies were of poor quality.

10.1002/14651858.CD001781.pub3

cochrane-simplification-train-2314

cochrane-simplification-train-2314

The search identified two randomized controlled trials for inclusion. One trial included 47 hypertensive patients and showed that garlic significantly reduces mean supine systolic blood pressure by 12 mmHg (95% CI 0.56 to 23.44 mmHg, p=0.04) and mean supine diastolic blood pressure by 9 mmHg (95% CI 2.49 to 15.51 mmHg, p=0.007) versus placebo. The authors state that garlic was "free from side effects" and that no serious side effects were reported. There were 3 cases "where a slight smell of garlic was noted." The second trial could not be meta-analysed as they did not report the number of people randomized to each treatment group. They did report that 200 mg of garlic powder given three times daily, in addition to hydrochlorothiazide-triamterene baseline therapy, produced a mean reduction of systolic blood pressure by 10-11 mmHg and of diastolic blood pressure by 6-8 mmHg versus placebo. Neither trial reported clinical outcomes and insufficient data was provided on adverse events. There is insufficient evidence to determine if garlic provides a therapeutic advantage versus placebo in terms of reducing the risk of mortality and cardiovascular morbidity in patients diagnosed with hypertension. There is also insufficient evidence to determine the difference in withdrawals due to adverse events between patients treated with garlic or placebo. Based on 2 trials in 87 hypertensive patients, it appears that garlic reduces mean supine systolic and diastolic blood pressure by approximately 10-12 mmHg and 6-9 mmHg, respectively, over and above the effect of placebo but the confidence intervals for these effect estimates are not precise and this difference in blood pressure reduction falls within the known variability in blood pressure measurements. This makes it difficult to determine the true impact of garlic on lowering blood pressure.

In this analysis, we reviewed the currently available evidence to determine the impact of garlic on cardiovascular events and mortality in patients with hypertension. Based on data from two randomized controlled trials that compared garlic to placebo in patients with hypertension it appears that garlic may have some blood pressure lowering effect, as compared to placebo but the evidence currently available is insufficient to determine whether garlic provides a therapeutic advantage versus placebo in terms of reducing the risk of cardiovascular morbidity and mortality. Data on the safety of garlic, as a therapeutic entity, in this population is also lacking. More (and large enough) trials comparing several doses of garlic with placebo are needed to detect possible differences in mortality, serious adverse events, and cardiovascular morbidity.

10.1002/14651858.CD007653.pub2

cochrane-simplification-train-2315

cochrane-simplification-train-2315

Seventy-eight randomised trials with 296,707 participants were included. Fifty-six trials including 244,056 participants had low risk of bias. Twenty-six trials included 215,900 healthy participants. Fifty-two trials included 80,807 participants with various diseases in a stable phase. The mean age was 63 years (range 18 to 103 years). The mean proportion of women was 46%. Of the 78 trials, 46 used the parallel-group design, 30 the factorial design, and 2 the cross-over design. All antioxidants were administered orally, either alone or in combination with vitamins, minerals, or other interventions. The duration of supplementation varied from 28 days to 12 years (mean duration 3 years; median duration 2 years). Overall, the antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (21,484 dead/183,749 (11.7%) versus 11,479 dead/112,958 (10.2%); 78 trials, relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05) but significantly increased mortality in a fixed-effect model (RR 1.03, 95% CI 1.01 to 1.05). Heterogeneity was low with an I2- of 12%. In meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. Meta-regression analysis did not find a significant difference in the estimated intervention effect in the primary prevention and the secondary prevention trials. In the 56 trials with a low risk of bias, the antioxidant supplements significantly increased mortality (18,833 dead/146,320 (12.9%) versus 10,320 dead/97,736 (10.6%); RR 1.04, 95% CI 1.01 to 1.07). This effect was confirmed by trial sequential analysis. Excluding factorial trials with potential confounding showed that 38 trials with low risk of bias demonstrated a significant increase in mortality (2822 dead/26,903 (10.5%) versus 2473 dead/26,052 (9.5%); RR 1.10, 95% CI 1.05 to 1.15). In trials with low risk of bias, beta-carotene (13,202 dead/96,003 (13.8%) versus 8556 dead/77,003 (11.1%); 26 trials, RR 1.05, 95% CI 1.01 to 1.09) and vitamin E (11,689 dead/97,523 (12.0%) versus 7561 dead/73,721 (10.3%); 46 trials, RR 1.03, 95% CI 1.00 to 1.05) significantly increased mortality, whereas vitamin A (3444 dead/24,596 (14.0%) versus 2249 dead/16,548 (13.6%); 12 trials, RR 1.07, 95% CI 0.97 to 1.18), vitamin C (3637 dead/36,659 (9.9%) versus 2717 dead/29,283 (9.3%); 29 trials, RR 1.02, 95% CI 0.98 to 1.07), and selenium (2670 dead/39,779 (6.7%) versus 1468 dead/22,961 (6.4%); 17 trials, RR 0.97, 95% CI 0.91 to 1.03) did not significantly affect mortality. In univariate meta-regression analysis, the dose of vitamin A was significantly associated with increased mortality (RR 1.0006, 95% CI 1.0002 to 1.001, P = 0.002). We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.

Previous research on animal and physiological models suggests that antioxidant supplements have beneficial effects that may prolong life. Some observational studies also suggest that antioxidant supplements may prolong life, whereas other observational studies demonstrate neutral or harmful effects. Our Cochrane review from 2008 demonstrated that antioxidant supplements seem to increase mortality. This review is now updated. The present systematic review included 78 randomised clinical trials. In total, 296,707 participants were randomised to antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Twenty-six trials included 215,900 healthy participants. Fifty-two trials included 80,807 participants with various diseases in a stable phase (including gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified diseases). A total of 21,484 of 183,749 participants (11.7%) randomised to antioxidant supplements and 11,479 of 112,958 participants (10.2%) randomised to placebo or no intervention died. The trials appeared to have enough statistical similarity that they could be combined. When all of the trials were combined, antioxidants may or may not have increased mortality depending on which statistical combination method was employed; the analysis that is typically used when similarity is present demonstrated that antioxidant use did slightly increase mortality (that is, the patients consuming the antioxidants were 1.03 times as likely to die as were the controls). When analyses were done to identify factors that were associated with this finding, the two factors identified were better methodology to prevent bias from being a factor in the trial (trials with ‘low risk of bias’) and the use of vitamin A. In fact, when the trials with low risks of bias were considered separately, the increased mortality was even more pronounced (1.04 times as likely to die as were the controls). The potential damage from vitamin A disappeared when only the low risks of bias trials were considered. The increased risk of mortality was associated with beta-carotene and possibly vitamin E and vitamin A, but was not associated with the use of vitamin C or selenium. The current evidence does not support the use of antioxidant supplements in the general population or in patients with various diseases.

10.1002/14651858.CD007176.pub2

cochrane-simplification-train-2316

cochrane-simplification-train-2316

Nine studies were identified, five of which met the inclusion criteria. A meta-analysis of two trials in which 71 patients were randomized to nicotine and 70 to placebo showed a statistically significant benefit for nicotine treatment. After four to six weeks of treatment 19 of 71 patients treated with transdermal nicotine were in clinical remission compared to 9 of 70 treated with placebo (OR=2.56, 95% CI 1.02-6.45). In the same group of patients improvement or remission was noted in 29 of the 71 patients assigned to nicotine compared to 14 of 70 patients assigned to placebo (OR=2.72, 95% CI 1.28 - 5.81). For patients with left sided colitis the odds ratio was 2.31 (95% CI 1.05-5.10). When transdermal nicotine was compared to standard medical therapy no significant benefit for nicotine was observed. After four to six weeks of standard therapy (oral prednisone or mesalamine), 34 of 63 patients were in clinical or sigmoidoscopic remission compared to 33 of 66 patients treated with transdermal nicotine (OR=0.77, 95% CI 0.37-1.60). A meta-analysis of all five studies which included 137 patients treated with transdermal nicotine and 133 patients treated with a placebo or standard therapy demonstrated no statistically significant benefit of nicotine therapy (OR=1.23; 95% CI 0.71-2.14). Patients treated with transdermal nicotine were significantly more likely to withdrawal due to adverse events than patients treated with placebo or standard medical therapy (OR=5.82, 95% CI, 1.66 - 20.47) and were significantly more likely to suffer from an adverse event than patients treated with placebo or standard medical therapy (OR=3.54, 95% CI, 2.07 - 6.08). The results of this review provide evidence that transdermal nicotine is superior to placebo for the induction of remission in patient's with ulcerative colitis. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy. Adverse events associated with transdermal nicotine are significant and limit its use in some patients.

Randomised controlled trials were therefore developed to test the hypothesis that nicotine patches can induce remission of a flare of ulcerative colitis. This review provides evidence that transdermal nicotine is superior to placebo (fake patch) for the treatment of active ulcerative colitis. However, patients treated with transdermal nicotine were significantly more likely to experience side effects than patients receiving placebo or standard medical therapy. Its use is therefore limited in some patients. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy.

10.1002/14651858.CD004722.pub2

cochrane-simplification-train-2317

cochrane-simplification-train-2317

One trial, which included 49 infants, met the inclusion criteria. The trial compared the use of inhaled corticosteroids (budesonide) with placebo. We found no differences between groups in terms of need for nasal continuous positive airway pressure (risk ratio (RR) 1.27, 95% confidence interval (CI) 0.65 to 2.51; 1 study, 49 participants) and need for mechanical ventilation (RR 0.52, 95% CI 0.05 to 5.38; 1 study, 49 participants). The type of mechanical ventilation used in the included study was high-frequency oscillation. Tests for heterogeneity were not applicable for any of the analyses as only one study was included. Out of the secondary outcomes we deemed to be of greatest importance to patients, the study only reported on duration of hospital stay, which was no different between groups. The quality of the evidence is very low, due to the imprecision of the estimates and indirectness. We identified no ongoing trials. Given the paucity and very low quality of the available evidence, we are unable to determine the benefits and harms of postnatal administration of either inhaled or systemic corticosteroids for the management of TTN.

We identified and included one study, which compared steroids with placebo (dummy pill) in 49 newborns. The steroids were given to babies by inhalation. We found no ongoing studies. The evidence is up to date as of February 2019. Steroids did not improve lung function or reduce the need for breathing support. Overall, we are uncertain as to whether steroids have an important effect on rapid breathing because the results are imprecise and based on only one small study.

10.1002/14651858.CD013222.pub2

cochrane-simplification-train-2318

cochrane-simplification-train-2318

We included 29 studies involving 5392 participants (mean age = 64 years, age range 23 to 86 years, 82% male). However, few studies contributed data to meta-analyses due to inconsistency in outcome definition and reporting. In general, risk of bias varied from low to high risk of bias across included studies, and insufficient detail was provided to inform judgement in several cases. The quality of the evidence of key outcomes ranged from moderate to low quality due to the presence of moderate or high statistical heterogeneity, imprecision of results or due to limitations in the design of individual studies. Compared with no RIPC, we found that RIPC has no treatment effect on the rate of the composite endpoint with RR 0.99 (95% confidence interval (CI) 0.78 to 1.25); 2 studies; 2463 participants; moderate-quality evidence. Participants randomised to RIPC showed an equivalent or better effect regarding the amount of cTnT release measured at 72 hours after surgery with SMD -0.32 (95% CI -0.65 to 0.00); 3 studies; 1120 participants; moderate-quality evidence; and expressed as AUC 72 hours with SMD -0.49 (95% CI -0.96 to -0.02); 3 studies; 830 participants; moderate-quality evidence. We found the same result in favour of RIPC for the cTnI release measured at 48 hours with SMD -0.21 (95% CI -0.40 to -0.02); 5 studies; 745 participants; moderate-quality evidence; and measured at 72 hours after surgery with SMD -0.37 (95% CI -0.59 to -0.15); 2 studies; 459 participants; moderate-quality evidence. All other primary outcomes showed no differences between groups (cTnT release measured at 48 hours with SMD -0.14, 95% CI -0.33 to 0.06; 4 studies; 1792 participants; low-quality evidence and cTnI release measured as AUC 72 hours with SMD -0.17, 95% CI -0.48 to 0.14; 2 studies; 159 participants; moderate-quality evidence). We also found no differences between groups for all-cause mortality after 30 days, non-fatal myocardial infarction after 30 days, any new stroke after 30 days, acute renal failure after 30 days, length of stay on the intensive care unit (days), any complications and adverse effects related to ischaemic preconditioning. We did not assess many patient-centred/salutogenic-focused outcomes. We found no evidence that RIPC has a treatment effect on clinical outcomes (measured as a composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke, or both, assessed at 30 days after surgery). There is moderate-quality evidence that RIPC has no treatment effect on the rate of the composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke assessed at 30 days after surgery, or both. We found moderate-quality evidence that RIPC reduces the cTnT release measured at 72 hours after surgery and expressed as AUC (72 hours). There is moderate-quality evidence that RIPC reduces the amount of cTnI release measured at 48 hours, and measured 72 hours after surgery. Adequately-designed studies, especially focusing on influencing factors, e.g. with regard to anaesthetic management, are encouraged and should systematically analyse the commonly used medications of people with cardiovascular diseases.

We searched scientific databases for randomised trials in which people scheduled for CABG (with or without valve surgery) were randomly assigned to receive RIPC or sham intervention before surgery. The evidence is current to May 2016. We did not identify any source of bias related to the funding of included studies. We identified 29 studies involving 5392 participants (mean age = 64 years, age range 23 to 86 years, 82% male). RIPC does not improve clinical outcome in people undergoing CABG with or without valve surgery (measured as a composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke, or both, assessed at 30 days after surgery, moderate-quality evidence). There is moderate-quality evidence that RIPC reduces the amount of cardiac troponin T release measured at 72 hours and measured as AUC (72 hours). There is moderate-quality evidence that cardiac troponin I release measured at 48 hours and 72 hours after surgery is lower in the RIPC group than in the control group. Regarding troponin T measured at 48 hours and troponin I measured as AUC 72 hours after surgery there was no difference between groups (low- and moderate-quality evidence). However, this effect on biomarkers does not result in improved clinical outcome. We used reliable methods to assess the quality of the trial evidence. The quality of the evidence of key outcomes ranged from moderate to low quality due to the presence of moderate or high statistical heterogeneity, imprecision of results or due to limitations in the design of individual studies.

10.1002/14651858.CD011719.pub3

cochrane-simplification-train-2319

cochrane-simplification-train-2319

In the first version of this review there were six eligible trials concerning 649 participants comparing plasma exchange with supportive treatment. No new eligible trials have been identified in subsequent updates. Two other studies compared different numbers of plasma exchanges. Overall the included trials had a moderate risk of bias (in general, the studies were at low risk but all had a high risk of bias from lack of blinding). In one trial with 220 severely affected participants, the median time to recover walking with aid was significantly shorter with plasma exchange (30 days) than without plasma exchange (44 days). In another trial with 91 mildly affected participants, the median time to onset of motor recovery was significantly shorter with plasma exchange (six days) than without plasma exchange (10 days). After four weeks, moderate-quality evidence from the combined data of three trials accounting for a total of 349 patients showed that plasma exchange significantly increased the proportion of patients who recovered the ability to walk with assistance (risk ratio (RR) 1.60, 95% confidence interval (CI) 1.19 to 2.15). In five trials with 623 participants in total, moderate-quality evidence showed that the RR for improvement by one or more disability grades after four weeks was 1.64 (95% CI 1.37 to 1.96) times greater with plasma exchange. Participants treated with plasma exchange also fared better, according to moderate-quality evidence, in time to recover walking without aid (three trials with 349 participants; RR 1.72, 95% CI 1.06 to 2.79) and requirement for artificial ventilation (five trials with 623 participants; RR 0.53, 95% CI 0.39 to 0.74). More participants had relapses by the end of follow-up in the plasma exchange group than in the control group (six trials with 649 participants; RR 2.89, 95% CI 1.05 to 7.93; moderate-quality evidence). Despite this, according to moderate-quality evidence, the likelihood of full muscle strength recovery at one year was greater with plasma exchange than without plasma exchange (five trials with 404 participants; RR 1.24, 95% CI 1.07 to 1.45), and the likelihood of severe motor sequelae was less (six trials with 649 participants; RR 0.65, 95% CI 0.44 to 0.96). High-quality evidence from six trials with 649 participants could not confirm or refute a lower risk of death following plasma exchange compared to control (RR 0.86, 95% CI 0.45 to 1.65). Three trials (N = 556) provided details of serious adverse events during the hospital stay; combined analyses found no increase in serious infectious events compared to the control group (RR 0.91, 95% CI 0.73 to 1.13), nor were there clear differences in blood pressure instability, cardiac arrhythmias or pulmonary emboli. Moderate-quality evidence shows significantly more improvement with plasma exchange than with supportive care alone in adults with Guillain-Barré syndrome, without a significant increase in serious adverse events. According to moderate-quality evidence, there was a small but significant increase in the risk of relapse during the first six to 12 months after onset in people treated with plasma exchange compared with those who were not treated. Despite this, after one year, full recovery of muscle strength was more likely and severe residual weakness less likely with plasma exchange.

We carried out a wide search of medical databases for trials in which participants were randomly assigned to plasma exchange or no treatment except supportive care. We found six trials, which included 649 participants in total. All six trials compared plasma exchange with supportive treatment. All were at low risk of bias, except that participants and their carers were aware of the treatment given (they were not blinded). Two additional studies compared different numbers of plasma exchange and could not be included in the analysis but are discussed. Plasma exchange speeded improvement from GBS. It did not cause harm apart from being followed by a probable slight increase in risk of relapse. Despite this, plasma exchange probably increases the chance of complete muscle strength recovery after one year. No new trials have been done since the first publication of this review in 2001. However trials have been done comparing plasma exchange with intravenous infusion of human immune globulin (the antibody portion of plasma). These trials are included in another Cochrane review and show the effects of the two treatments are similar. The evidence is up to date to 18 January 2016.

10.1002/14651858.CD001798.pub3

cochrane-simplification-train-2320

cochrane-simplification-train-2320

Four trials were included. These involved a total of 278, mainly adult, participants with 283 mallet finger injuries. All four trials were methodologically flawed, including inadequate outcome assessment. Three trials compared different types of finger splints versus a standard Stack splint. One trial found a lower incidence of treatment failure in participants treated with a perforated custom-made splint. One trial found there were fewer complications in participants treated with a padded aluminium-alloy malleable finger splint; however, the incidence of treatment failure was similar in the two treatment groups. One trial evaluating the Abouna splint found a similar incidence of treatment failure in the two groups. However, the Abouna splint often needed replacing due to disintegration of its rubber cover and rusting of the exposed wires and was also less popular with participants. The fourth trial found no statistically significant differences between participants whose mallet finger was treated with Kirschner wire fixation and those with a Pryor and Howard splint. Similar numbers had complications in the two groups. There was insufficient evidence from comparisons tested within randomised controlled trials to establish the relative effectiveness of different, either custom-made or off-the-shelf, finger splints used for treating mallet finger injury. There was a useful reminder that splints used for prolonged immobilisation should be robust enough for everyday use, and of the central importance of patient adherence to instructions for splint use. There was insufficient evidence to determine when surgery is indicated.

Four randomised trials were included in the review. These involved a total of 278, mainly adult, participants with 283 mallet finger injuries. The methods of all four trials were flawed leading to concerns about bias. There was no pooling of data. Three trials compared different types of finger splints versus a standard Stack splint. One trial found less treatment failure in participants treated with a perforated custom-made splint. A second trial found there were fewer complications in participants treated with a padded aluminium-alloy malleable finger splint. However, the incidence of treatment failure was similar in the two treatment groups of this trial. The third trial evaluated the Abouna splint and found a similar incidence of treatment failure in the two groups. However, the Abouna splint often needed replacing due to disintegration of its rubber cover and rusting of the exposed wires and was also less popular with participants. The fourth trial in the review found no significant differences between participants whose mallet finger was treated with Kirschner wire fixation and those with a Pryor and Howard splint. Similar numbers had complications in the two groups. The review concluded that there was not enough evidence to show which is the best way to treat mallet finger injury. It noted, however, that splints used for prolonged immobilisation should be robust enough for everyday use.

10.1002/14651858.CD004574.pub2

cochrane-simplification-train-2321

cochrane-simplification-train-2321

Routine/revealed ultrasound versus selective ultrasound/concealed: 11 trials including 37,505 women. Ultrasound for fetal assessment in early pregnancy reduces the failure to detect multiple pregnancy by 24 weeks' gestation (risk ratio (RR) 0.07, 95% confidence interval (CI) 0.03 to 0.17; participants = 295; studies = 7), moderate quality of evidence). Routine scans improve the detection of major fetal abnormality before 24 weeks' gestation (RR 3.46, 95% CI 1.67 to 7.14; participants = 387; studies = 2,moderate quality of evidence). Routine scan is associated with a reduction in inductions of labour for 'post term' pregnancy (RR 0.59, 95% CI 0.42 to 0.83; participants = 25,516; studies = 8), but the evidence related to this outcome is of low quality, because most of the pooled effect was provided by studies with design limitation with presence of heterogeneity (I² = 68%). Ultrasound for fetal assessment in early pregnancy does not impact on perinatal death (defined as stillbirth after trial entry, or death of a liveborn infant up to 28 days of age) (RR 0.89, 95% CI 0.70 to 1.12; participants = 35,735; studies = 10, low quality evidence). Routine scans do not seem to be associated with reductions in adverse outcomes for babies or in health service use by mothers and babies. Long-term follow-up of children exposed to scan in utero does not indicate that scans have a detrimental effect on children's physical or cognitive development. The review includes several large, well-designed trials but lack of blinding was a problem common to all studies and this may have an effect on some outcomes. The quality of evidence was assessed for all review primary outcomes and was judged as moderate or low. Downgrading of evidence was based on including studies with design limitations, imprecision of results and presence of heterogeneity. Early ultrasound improves the early detection of multiple pregnancies and improved gestational dating may result in fewer inductions for post maturity. Caution needs to be exercised in interpreting the results of aspects of this review in view of the fact that there is considerable variability in both the timing and the number of scans women received.

The focus of this review is routine early pregnancy ultrasound (before 24 weeks). We included 11 randomised controlled trials involving 37,505 women. Early ultrasound improved the early detection of multiple pregnancies and improved gestational dating, which may result in fewer inductions for post maturity. The detection of fetal malformation was addressed in detail in only two of the trials. There was no evidence of a significant difference between the screened and control groups for perinatal death. Results do not show that routine scans reduce adverse outcomes for babies or lead to less health service use by mothers and babies. Long-term follow-up of children exposed to scans before birth did not indicate that scans have a detrimental effect on children's physical or intellectual development. Studies were carried out over three decades and technical advances in equipment, more widespread use of ultrasonography, and increased training and expertise of operators may have resulted in more effective sonography.

10.1002/14651858.CD007058.pub3

cochrane-simplification-train-2322

cochrane-simplification-train-2322

We included two randomised trials with 615 participants. Both studies delivered real-time video counselling for smoking cessation individually, compared with telephone counselling. We judged one study at unclear risk of bias and one study at high risk of bias. There was no statistically significant treatment effect for smoking cessation (using the strictest definition and longest follow-up) across the two included studies when real-time video counselling was compared to telephone counselling (risk ratio (RR) 2.15, 95% confidence interval (CI) 0.38 to 12.04; 2 studies, 608 participants; I2 = 66%). We judged the overall certainty of the evidence for smoking cessation as very low due to methodological limitations, imprecision in the effect estimate reflected by the wide 95% CIs and inconsistency of cessation rates. There were no significant differences between real-time video counselling and telephone counselling reported for number of quit attempts among people who continued to smoke (mean difference (MD) 0.50, 95% CI –0.60 to 1.60; 1 study, 499 participants), mean number of counselling sessions completed (MD –0.20, 95% CI –0.45 to 0.05; 1 study, 566 participants), completion of all sessions (RR 1.13, 95% CI 0.71 to 1.79; 1 study, 43 participants) or therapeutic alliance (MD 1.13, 95% CI –0.24 to 2.50; 1 study, 398 participants). Participants in the video counselling arm were more likely than their telephone counselling counterparts to recommend the programme to a friend or family member (RR 1.06, 95% CI 1.01 to 1.11; 1 study, 398 participants); however, there were no between-group differences on satisfaction score (MD 0.70, 95% CI –1.16 to 2.56; 1 study, 29 participants). There is very little evidence about the effectiveness of real-time video counselling for smoking cessation. The existing research does not suggest a difference between video counselling and telephone counselling for assisting people to quit smoking. However, given the very low GRADE rating due to methodological limitations in the design, imprecision of the effect estimate and inconsistency of cessation rates, the smoking cessation results should be interpreted cautiously. High-quality randomised trials comparing real-time video counselling to telephone counselling are needed to increase the confidence of the effect estimate. Furthermore, there is currently no evidence comparing real-time video counselling to a control group. Such research is needed to determine whether video counselling increases smoking cessation.

We searched for studies on 13 August 2019, and found two that met our inclusion criteria. Our main focus was to learn if video counselling delivered individually or to a group could help people quit smoking and to learn how it compared with other types of support to help people quit. We also studied the effect of real-time video counselling on the number of times people tried to quit, the number of sessions they completed, their satisfaction with the counselling, their relationship or bond with the counsellor and the costs of using video communication to help people quit smoking. Both studies took place in the USA, and included people from rural areas or women with HIV. Both studies gave one-to-one video sessions to individuals. There were eight video sessions in one study and four video sessions in the other study. Both studies compared video counselling to telephone counselling and looked at whether people quit smoking, the number of sessions they completed and their satisfaction with the programme. One study examined the number of times people tried to quit and one study looked at the relationship or bond with the counsellor. It is unclear how video counselling compares with telephone counselling in terms of helping people to quit smoking. People who used video counselling were more likely than those who used telephone counselling to recommend the programme to a friend or someone in their family, but we found no differences in how satisfied they were, the number of video or telephone sessions completed, whether all sessions were completed and in the relationship or bond with the counsellor. We rated the quality of the evidence for smoking cessation to be very low. There were only two studies, and the limitations in these studies made it difficult to draw reliable conclusions about whether video counselling can help people to quit smoking. This should be taken into account when looking at these findings.

10.1002/14651858.CD012659.pub2

cochrane-simplification-train-2323

cochrane-simplification-train-2323

We included 26 RCTs randomising 23,499 participants. All included studies assessed effects of ezetimibe plus other lipid-modifying drugs compared with other lipid-modifying drugs alone or plus placebo. Our findings were driven by the largest study (IMPROVE-IT), which had weights ranging from 41.5% to 98.4% in the different meta-analyses. Ezetimibe with statins probably reduces the risk of major adverse cardiovascular events compared with statins alone (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.90 to 0.98; a decrease from 284/1000 to 267/1000, 95% CI 256 to 278; 21,727 participants; 10 studies; moderate-quality evidence). Trials reporting all-cause mortality used ezetimibe with statin or fenofibrate and found they have little or no effect on this outcome (RR 0.98, 95% CI 0.91 to 1.05; 21,222 participants; 8 studies; high-quality evidence). Adding ezetimibe to statins probably reduces the risk of non-fatal myocardial infarction (MI) (RR 0.88, 95% CI 0.81 to 0.95; a decrease from 105/1000 to 92/1000, 95% CI 85 to 100; 21,145 participants; 6 studies; moderate-quality evidence) and non-fatal stroke (RR 0.83, 95% CI 0.71 to 0.97; a decrease 32/1000 to 27/1000, 95% CI 23 to 31; 21,205 participants; 6 studies; moderate-quality evidence). Trials reporting cardiovascular mortality added ezetimibe to statin or fenofibrate, probably having little or no effect on this outcome (RR 1.00, 95% CI 0.89 to 1.12; 19457 participants; 6 studies; moderate-quality evidence). The need for coronary revascularisation might be reduced by adding ezetimibe to statin (RR 0.94, 95% CI 0.89 to 0.99; a decrease from 196/1000 to 184/1000, 95% 175 to 194; 21,323 participants; 7 studies); however, no difference in coronary revascularisation rate was observed when a sensitivity analysis was limited to studies with a low risk of bias. In terms of safety, adding ezetimibe to statins may make little or no difference in the risk of hepatopathy (RR 1.14, 95% CI 0.96 to 1.35; 20,687 participants; 4 studies; low-quality evidence). It is uncertain whether ezetimibe increase or decrease the risk of myopathy (RR 1.31, 95% CI 0.72 to 2.38; 20,581 participants; 3 studies; very low-quality evidence) and rhabdomyolysis, given the wide CIs and low event rate. Little or no difference in the risk of cancer, gallbladder-related disease and discontinuation due to adverse events were observed between treatment groups. For serum lipids, adding ezetimibe to statin or fenofibrate might further reduce the low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglyceride levels and likely increase the high-density lipoprotein cholesterol levels; however, substantial heterogeneity was detected in most analyses. None of the included studies reported on health-related quality of life. Moderate- to high-quality evidence suggests that ezetimibe has modest beneficial effects on the risk of CVD endpoints, primarily driven by a reduction in non-fatal MI and non-fatal stroke, but it has little or no effect on clinical fatal endpoints. The cardiovascular benefit of ezetimibe might involve the reduction of LDL-C, total cholesterol and triglycerides. There is insufficient evidence to determine whether ezetimibe increases the risk of adverse events due to the low and very low quality of the evidence. The evidence for beneficial effects was mainly obtained from individuals with established atherosclerotic cardiovascular disease (ASCVD, predominantly with acute coronary syndrome) administered ezetimibe plus statins. However, there is limited evidence regarding the role of ezetimibe in primary prevention and the effects of ezetimibe monotherapy in the prevention of CVD, and these topics thus requires further investigation.

This evidence is current up to July 2018. We included 26 studies involving 23,499 participants. These studies assessed the effects of ezetimibe plus other lipid-lowering drugs versus lipid-lowering drugs alone for heart disease. The participants were adults, and most of them had been diagnosed with coronary heart disease. Ezetimibe with statins probably reduces the risk for combined outcome of death due to heart disease, heart attack or stroke, but the benefit is moderate. However, adding ezetimibe to statin or fenofibrate have little or no effect on death from any cause. Treatment with ezetimibe and statin probably reduces the risk for non-fatal heart attacks and non-fatal stroke. Adding ezetimibe to statin or fenofibrate probably have little or no effect on heart-related death. Ezetimibe with statins might reduce the need for coronary revascularisation (the restoration of an adequate blood supply to the heart) by means of surgery. In terms of safety, we do not have enough evidence to know whether ezetimibe increases or decreases side-effects (e.g. liver injury, muscle pain, cancer, gallbladder-related disease and discontinuation). The analysis of blood lipids revealed that the addition of ezetimibe statin or fenofibrate therapy might further reduce the levels of blood lipids, including low-density lipoprotein cholesterol ('bad' cholesterol), total cholesterol and triglycerides, and likely increased the level of high-density lipoprotein cholesterol ('good' cholesterol). None of the included studies reported on health-related quality of life. There is a lack of evidence supporting the use of ezetimibe monotherapy for the prevention of heart disease, and this topic requires further investigation. The quality of evidence ranged from high to very low across the outcomes.

10.1002/14651858.CD012502.pub2

cochrane-simplification-train-2324

cochrane-simplification-train-2324

We included three RCTs (327 children) which were assessed at low to moderate risk of bias. One RCT included 219 children with AOM, and used a three-arm, parallel group, double-blind design to compare paracetamol versus ibuprofen versus placebo. All children also received antibiotics and those with fever > 39 °C could have received paracetamol (30 mg to 60 mg) additionally to the studied treatments. Another RCT involved 156 febrile children (26 of whom had AOM). The study design was a three-arm, parallel group, double-blind design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol. The third RCT included 889 children with respiratory tract infections (82 of whom had AOM). This study applied a 3 x 2 x 2 factorial, open-label design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol. Study participants were randomised to one of the three treatment groups as well as two dosing groups (regular versus as required) and two steam inhalation groups (steam versus no steam). Authors of two RCTs provided crude subgroup data on children with AOM. We used data from the remaining trial to inform comparison of paracetamol versus placebo (148 children) and ibuprofen versus placebo (146 children) assessments. Data from all included RCTs informed comparison of ibuprofen versus paracetamol (183 children); data from the two RCTs informed comparison of ibuprofen plus paracetamol versus paracetamol alone (71 children). We found evidence, albeit of low quality, that both paracetamol and ibuprofen as monotherapies were more effective than placebo in relieving pain at 48 hours (paracetamol versus placebo: proportion of children with pain 10% versus 25%, RR 0.38, 95% CI 0.17 to 0.85; number needed to treat to benefit (NNTB) 7; ibuprofen versus placebo: proportion of children with pain 7% versus 25%, RR 0.28, 95% CI 0.11 to 0.70; NNTB 6). Very low quality evidence suggested that adverse events did not significantly differ between children treated with either paracetamol, ibuprofen or placebo. We found insufficient evidence of a difference between ibuprofen and paracetamol in relieving ear pain at 24 hours (2 RCTs, 39 children; RR 0.83, 95% CI 0.59 to 1.18; very low quality evidence), 48 to 72 hours (3 RCTs, 183 children; RR 0.91, 95% CI 0.54 to 1.54; low quality evidence) and four to seven days (2 RCTs, 38 children; RR 0.74, 95% CI 0.17 to 3.23; very low quality evidence). Data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone came from two RCTs that provided crude subgroup data for 71 children with AOM. The small sample provided imprecise effect estimates and we were consequently unable to draw any firm conclusions (very low quality evidence). Despite explicit guideline recommendations on its use, current evidence on the effectiveness of paracetamol or NSAIDs, alone or combined, in relieving pain in children with AOM is limited. Low quality evidence indicates that both paracetamol and ibuprofen as monotherapies are more effective than placebo in relieving short-term ear pain in children with AOM. There is insufficient evidence of a difference between ibuprofen and paracetamol in relieving short-term ear pain in children with AOM, whereas data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone were insufficient to draw any firm conclusions. Further research is needed to provide insights into the role of ibuprofen as adjunct to paracetamol, and other analgesics such as anaesthetic eardrops, for children with AOM.

We included data from three trials of low to moderate risk of bias of 327 children with AOM. One trial (219 children) compared paracetamol versus ibuprofen versus a dummy drug in children with AOM. In this trial, all children also received antibiotic treatment and those with fever > 39 °C may have received paracetamol in addition to the studied treatments. Two other trials compared the effects of paracetamol versus ibuprofen versus ibuprofen plus paracetamol in children with fever and patients with respiratory tract infections, respectively. The authors of these two trials provided crude subgroup data on children with AOM (26 and 82 children, respectively). In one trial, paracetamol, ibuprofen and a dummy drug were supplied by a pharmaceutical company (Ethypharm). No further details were provided about the role of this company in the design, conduct, analysis, or reporting of the trial. The other two trials were funded by governmental (non-commercial) grants. In one trial the drugs were purchased from and provided by two companies (Pfizer and DHP Investigational Medicinal Products) which had no role in the design, conduct, analysis, or reporting of the trial. Very limited information was available to assess how useful painkillers are for relieving children's pain due to AOM. We found that both paracetamol and ibuprofen when used alone were more effective than a dummy drug in relieving ear pain at 48 hours (25% of children receiving a dummy drug had residual pain at 48 hours versus 10% in the paracetamol group and 7% in the ibuprofen group). The adverse events reported in the trials did not significantly differ between children treated with either paracetamol, ibuprofen or dummy drug, but this finding should be interpreted cautiously, given there were few participants, and infrequent occurrence of adverse events. We found insufficient evidence of a difference between paracetamol and ibuprofen in relieving short-term (at 24 hours, 48 to 72 hours and 4 to 7 days) ear pain in children with AOM. We could not draw any firm conclusions on the effects of ibuprofen plus paracetamol versus paracetamol alone in relieving ear pain in children with AOM mainly because of the very limited number of participants (very small sample size). Evidence quality for ear pain relief at 48 hours for the comparisons paracetamol versus a dummy drug and ibuprofen versus a dummy drug was judged low (study limitations and questions about the applicability of evidence affected our confidence in the results); the quality of evidence for adverse events was judged very low (study limitations, small sample size and infrequent occurrence of adverse events affected our confidence in the results). Evidence quality for ear pain relief at 48 to 72 hours for the comparison ibuprofen versus paracetamol was judged low (study limitations and questions about the applicability of evidence affected our confidence in the results); the quality of evidence for ear pain relief at 24 hours and four to seven days was judged very low (study limitations and very small sample size affected our confidence in the results). Evidence quality for all outcomes in the trials comparing ibuprofen plus paracetamol versus paracetamol alone was very low (study limitations and very small sample size affected our confidence in the results).

10.1002/14651858.CD011534.pub2

cochrane-simplification-train-2325

cochrane-simplification-train-2325

We included a total of 13 randomised trials with 790 patients. Loss of hepatitis B 'e' antigen (OR 1.41, 95% confidence interval 1.03 to 1.92, P = 0.03) and hepatitis B virus DNA (OR = 1.51, 95% confidence interval 1.12 to 2.05, P = 0.008) were significantly more frequent among patients treated with the sequential combination of glucocorticosteroids and alfa interferon than among patients treated with alfa interferon alone. Glucocorticosteroid pretreatment did not significantly influence seroconversion from hepatitis B 'e' antigen to antibodies to hepatitis B 'e' antigen, loss of hepatitis B surface antigen, normalisation of alanine aminotransferase/aspartate aminotransferase activities, and severity of adverse events. Glucocorticosteroid pretreatment did not significantly affect mortality and adverse events. The effect of glucocorticosteroid pretreatment on liver histology and quality of life could not be assessed due to insufficient data. Pretreatment with glucocorticosteroids before treatment with alfa interferon in patients with hepatitis B 'e' antigen positive chronic hepatitis B may be more effective than treatment with alfa interferon alone with regard to loss of hepatitis B 'e' antigen and hepatitis B virus DNA, but evidence for effect on clinical outcomes is lacking.

The objectives of this review were to assess the effects of the sequential combination of glucocorticosteroids and interferon compared to interferon alone in the treatment of chronic hepatitis B. Glucocorticosteroid pretreatment was associated with a significantly higher frequency of loss of hepatitis B markers (HBeAg and HBV DNA), but had no significant effect on clinical outcomes.

10.1002/14651858.CD000345.pub2

cochrane-simplification-train-2326

cochrane-simplification-train-2326

The search retrieved 62 reports in total. Of these, we assessed 12 reports in full, corresponding to six trials. We included three trials and excluded one; two trials are ongoing. The included trials were conducted in hospital settings. Two trials were conducted in India; the third trial was a large cluster-randomised trial, which took place in 13 European countries. Overall, we judged the included trials to be at a low risk of bias. One study evaluated the use of calibrated drapes versus visual estimation, another evaluated the use of calibrated drapes versus the gravimetric technique (weight of blood-soaked materials), therefore, we were unable to pool the data from the two studies. The third study did not measure any of the outcomes of interest, so did not contribute data to the analyses. Direct measurement using calibrated drapes versus visual estimation One cluster-randomised controlled trial in 13 western European countries, with over 25,000 women, examined this comparison. The trial did not report on postpartum anaemia (defined as Hb lower than 9 mg/dL), blood loss greater than 500 mL, or maternal infection. Moderate-quality evidence suggests there is probably little or no difference between groups in: severe morbidity (coagulopathy, organ failure, intensive care unit admission; adjusted risk ratio (RR) 0.82, 95% confidence interval (CI) 0.48 to 1.39); the risk of blood transfusion (adjusted RR 0.82, 95% CI 0.46 to 1.46); the use of plasma expanders (adjusted RR 0.77, 95% CI 0.42 to 1.42); and the use of therapeutic uterotonics (adjusted RR 0.87, 95% CI 0.42 to 1.76). Direct measurement using calibrated drapes (Excellent BRASSS-V Drape™) versus gravimetric technique One randomised controlled trial in India, with 900 women, examined this comparison. The trial did not report on postpartum anaemia (defined as Hb lower than 9 mg/dL), severe morbidity, or maternal infection. High-quality evidence showed that using calibrated drapes improved the detection of blood loss greater than 500 mL when compared with the gravimetric technique (RR 1.86, 95% CI 1.11 to 3.11). Low-quality evidence suggests there may be little or no difference in the risk of blood transfusion between the two groups (RR 1.00, 95% CI 0.06 to 15.94), or in the use of plasma expanders, reported as intravenous fluids given for PPH treatment (RR 0.67; 95% CI 0.19 to 2.35). High-quality evidence showed little or no difference in the use of therapeutic uterotonics (RR 1.01, 95% CI 0.90 to 1.13), but the use of therapeutic uterotonics was extremely high in both arms of the study (57% and 56%). Overall, the evidence in this review is insufficient to support the use of one method over another for blood loss estimation after vaginal birth. In general, the quality of evidence for our predefined outcomes ranged from low to high quality, with downgrading decisions due to imprecision. The included trials did not report on many of our primary and secondary outcomes. In trials that evaluate methods for estimating blood loss during vaginal birth, we believe it is important to measure their impact on clinical maternal and neonatal outcomes, along with their diagnostic accuracy. This body of knowledge needs further, well designed, appropriately powered, randomised controlled trials that correlate blood loss with relevant clinical outcomes, such as those listed in this review.

We searched for evidence in February 2018, and found three randomised controlled trials, involving over 26,000 women. Two trials contributed data to our analyses; one study did not provide data for any of the outcomes of interest in this review. All of the trials took place in hospital settings. Two trials took place in India, the other was conducted in 13 different European countries. The trials examined different methods of estimating blood loss. One trial (conducted in 13 European countries, involving over 25,000 women) compared the use of a calibrated drape (direct estimation) to visual estimation (indirect estimation). Moderate-quality evidence showed there was probably little or no difference between the methods for the risk of women developing serious conditions (e.g. failure to form clots, poor functioning of the liver, kidneys, and brain, admission to intensive care); their need for blood transfusion; the use of fluids to maintain their blood pressure; or the use of drugs to help their uterus contract to stop the bleeding. The trial did not report the number of women who had anaemia after birth, blood loss of at least 500 mL, or infection. One trial (conducted in India, involving 900 women) compared the use of a calibrated drape (direct estimation) to weighing and measuring blood and blood-soaked materials (indirect method). High-quality evidence showed that calibrated drapes were better than measuring the blood and blood-soaked materials at detecting blood loss of at least 500 mL. Low-quality evidence showed there may be little or no difference between methods in the need for blood transfusion or fluids to maintain blood pressure. High-quality evidence showed little or no difference in the use of drugs to help the uterus contract in order to stop bleeding. The trial did not report the number of women who had anaemia after birth or infection, or the risk of developing serious conditions (such as failure to form clots, poor functioning of the liver, kidneys, and brain, or being admitted to intensive care). There was insufficient evidence to support the use of one method over another to estimate blood loss after vaginal birth. There is a need for high quality trials that measure important outcomes, such as those listed in this review.

10.1002/14651858.CD010980.pub2

cochrane-simplification-train-2327

cochrane-simplification-train-2327

Six studies found since 2004 were originally viewed as possible inclusions, but when the family-centred score assessment was tested, only one met the minimum score of family-centredness and was included in this review. This was an unpublished RCT involving 288 children post-tonsillectomy in a care-by-parent unit (CBPU) compared with standard inpatient care.The study used a range of behavioural, economic and physical measures. It showed that children in the CBPU were significantly less likely to receive inadequate care compared with standard inpatient admission, and there were no significant differences for their behavioural outcomes or other physical outcomes. Parents were significantly more satisfied with CBPU care than standard care, assessed both before discharge and at 7 days after discharge. Costs were lower for CPBU care compared with standard inpatient care. No other outcomes were reported. The study was rated as being at low to unclear risk of bias. This update of a review has found limited, moderate-quality evidence that suggests some benefit of a family-centred care intervention for children's clinical care, parental satisfaction, and costs, but this is based on a small dataset and needs confirmation in larger RCTs. There is no evidence of harms. Overall, there continues to be little high-quality quantitative research available about the effects of family-centred care. Further rigorous research on the use of family-centred care as a model for care delivery to children and families in hospitals is needed. This research should implement well-developed family-centred care interventions, ideally in randomised trials. It should investigate diverse participant groups and clinical settings, and should assess a wide range of outcomes for children, parents, staff and health services.

This review has tried to do that by examining research about family-centred care. We looked for randomised trials of family-centred care interventions for children aged 0-12 years, in hospitals. We assessed potentially-relevant studies against criteria that identify important parts of family-centred care. Despite extensive searching we identified only one moderate-quality study (Bolton 2004) for inclusion. This study, from a doctoral thesis, showed that the family-centred care model had a positive effect on the adequacy of children's care, parental satisfaction, and costs. For other indicators such as clinical outcomes and children's behaviour there was no significant difference between the family-centred care model and standard inpatient care. There were no harms reported. In this searches for this update, we also found 25 qualitative studies which described aspects of family-centred care, and a review of these will be published by the Joanna Briggs Institute. Our main conclusion from this Cochrane review update, however, is that further, rigorous research is needed to assess the effects of family-centred care on children's experience of hospitalisation, as well as on their parents, hospital staff, and service delivery outcomes such as costs.

10.1002/14651858.CD004811.pub3

cochrane-simplification-train-2328

cochrane-simplification-train-2328

We included nine RCTs involving 725 women. However, five trials did not contribute data. Four trials involving 358 women contributed data. Trials were generally at mixed risk of bias. We only identified data for three comparisons: pharmaceutical treatment versus placebo or no treatment; acupuncture versus no treatment and pharmacological intervention versus advice on dietary and lifestyle changes. Pharmaceutical treatment compared with placebo or no treatment Two trials evaluated any pharmaceutical treatment compared with placebo or no treatment. One trial examined a treatment rarely used nowadays (intramuscular prostigmine 0.5 mg versus placebo). One trial evaluated the effect of magnesium and aluminium hydroxide plus simethicone liquid and tablet compared with placebo. For the primary outcome of this review (relief of heartburn), women who received pharmaceutical treatment reported complete heartburn relief more often than women receiving no treatment or placebo (risk ratio (RR) 1.85, 95% confidence interval (CI) 1.36 to 2.50 in two RCTs of 256 women, I2 = 0%, moderate-quality evidence). Data on partial relief of heartburn were heterogenous and showed no clear difference (average RR 1.35, 95% CI 0.38 to 4.76 in two RCTs of 256 women, very low-quality evidence). In terms of secondary outcomes, there was no clear difference in the rate of side effects between the pharmaceutical treatment group and the placebo/no treatment group (RR 0.63, 95% CI 0.21 to 1.89 in two RCTs of 256 women, very low-quality evidence). Pharmacological intervention versus advice on dietary and lifestyle choices One study compared 1 g of sucralfate with advice on dietary and lifestyle choices in treating heartburn. More women in the sucralfate group experienced complete relief of heartburn compared to women who received advice on diet and lifestyle choices (RR 2.41, 95% CI 1.42 to 4.07; participants = 65; studies = one). The only secondary outcome of interest addressed by this trial was side effects. The evidence was not clear on intervention side effects rate between the two groups (RR 1.74, 95% CI 0.07 to 41.21; participants = 66; studies = one). There was only one instance of side effects in the pharmacological group. Acupuncture compared with no treatment One trial evaluated acupuncture compared with no treatment but did not report data relating to this review's primary outcome (relief of heartburn). In terms of secondary outcomes, there was no difference in the rate of side effects between women who had acupuncture and women who had no treatment (RR 2.43, 95% CI 0.11 to 55.89 in one RCT of 36 women). With regard to quality of life, women who had acupuncture reported improved ability to sleep (RR 2.80, 95% CI 1.14 to 6.86) and eat (RR 2.40, 95% CI 1.11 to 5.18 in one RCT of 36 women). The following secondary outcomes were not reported upon in any of the trials included in the review: miscarriage, preterm labour, maternal satisfaction, fetal anomalies, intrauterine growth restriction, low birthweight. There are no large-scale RCTs to assess heartburn relief in pregnancy. This review of nine small studies (which involved data from only four small studies) indicates that there are limited data suggesting that heartburn in pregnancy could be completely relieved by pharmaceutical treatment. Three outcomes were assessed and assigned a quality rating using the GRADE methods. Evidence from two trials for the outcome of complete relief of heartburn was assessed as of moderate quality. Evidence for the outcomes of partial heartburn relief and side effects was graded to be of very low quality. Downgrading decisions were based in part on the small size of the trials and on heterogenous and imprecise results. There are insufficient data to assess acupuncture versus no treatment and no data to assess other comparisons (miscarriage, preterm labour, maternal satisfaction, fetal anomalies, intrauterine growth restriction, low birthweight). Further RCTs are needed to fully evaluate the effectiveness of interventions for heartburn in pregnancy. Future research should also address other medications such as histamine 2-receptor antagonists, promotility drugs, proton pump inhibitors, and a raft-forming alginate reflux suppressant in treatment of heartburn in pregnancy. More research is needed on acupuncture and other complimentary therapies as treatments for heartburn in pregnancy. Future research should also evaluate any adverse outcomes, maternal satisfaction with treatment and measure pregnant women's quality of life in relation to the intervention.

We found four small trials that provided data on 358 women. We estimated that the risk of bias was low for women enrolled in the study and the researchers as far as knowing if they were in the treatment group or the control (or placebo) group. It was unclear if there was a risk of bias for how the decisions were made to for women to be in the treatment or control/placebo groups, for those looking at the results and if all the results were reported. Two trials looked at medication compared with placebo or no treatment. One study examined the effect of a medication(sucralfate) in comparison to advice on dietary and lifestyle choice. One trial evaluated acupuncture versus no treatment. Women who received medication reported complete relief from heartburn more often than women receiving no treatment or placebo, or women who received advice on diet and lifestyle choices (moderate quality of evidence). We found no difference in partial relief of heartburn nor in side effects between the treatment groups (very low quality of evidence). We also found women who received acupuncture reported improved quality of life in terms of improved ability to sleep and eat, and no difference in the rate of side effects compared to women who received no acupuncture, From the little evidence there is, medication seems to help relieve heartburn but there is not enough data to say which medication is best. Acupuncture seems to help women to eat and sleep better when troubled with heartburn. Further research is needed to fully evaluate the effectiveness of interventions for heartburn in pregnancy. Future research should also address other medications such as histamine 2-receptor antagonists, promotility drugs, proton pump inhibitors, and a raft-forming alginate reflux suppressant in treatment of heartburn in pregnancy. More research is needed on acupuncture and other complimentary therapies as treatments for heartburn in pregnancy. Future research should also consider any adverse outcomes, maternal satisfaction with treatment and measure pregnant women's quality of life in relation to the intervention.

10.1002/14651858.CD011379.pub2

cochrane-simplification-train-2329

cochrane-simplification-train-2329

Only one study met the inclusion criteria, an RCT conducted in Tanzania between May 2003 and October 2004. Women in the intervention group (n=760) received a letter for their male partners, which invited them to return together to receive Couple Voluntary Counselling and Testing (CVCT) for HIV. Women in the control group (n=761) received individual HIV VCT during their first ANC visit and then usual care. The percentages of women who received HIV VCT and collected their results were 48%, 45% and 39% in the intervention group and 93%, 78% and 71% in the control group (p <0,001). Only 33% of women in the intervention group returned with their male partners and only 47% of them went through the whole CVCT process. The proportion of women who received HIV prophylaxis at delivery was not different between the two arms (27% in the intervention and 22% in the control group). The study had a high risk of bias. We found only one eligible study that assessed the effectiveness of male involvement in improving women’s uptake of PMTCT services, which only focused on one part of the perinatal PMTCT cascade. We urgently need more rigorously designed studies assessing the impact of male engagement interventions on women’s uptake of PMTCT services to know if this intervention can contribute to improve uptake of PMTCT services and reduce vertical transmission of HIV in children.

We undertook a comprehensive search to identify relevant studies. We found 3,072 references, but only one study that met our criteria. The study was performed in 2003-2004 in Tanzania. Pregnant women in the intervention group were provided with a letter inviting their male partners to accompany them to their next visit, in which they were offered voluntary HIV counselling and testing (VCT) together or separately. Women in the control group received the VCT individually during their first visit. The proportions of women that received VCT and collected their HIV test results were significantly lower in the intervention group than in the control group. Most of the women in the intervention group did not return to the clinic for the subsequent visit and most of those that returned accompanied refused to receive VCT together with their male partners. The invitation letter had a negative impact on the PMTCT uptake in that setting. We urgently need more studies assessing different interventions to improve male engagement in PMTCT to identify the most successful approach for women to safely access health care for their own health and to deliver HIV negative children.

10.1002/14651858.CD009468.pub2

cochrane-simplification-train-2330

cochrane-simplification-train-2330

Four studies, involving a total of 414 participants, met the inclusion criteria. Three studies were conducted in adult participants and one in adolescents. The average age of participants ranged from 14 to 43 years. The trials lasted between two months and 12 months. The interventions were based on Pennebaker's method. The risk of bias across most domains of the studies was generally considered to be low, however three of four studies were considered at high risk of bias due to lack of assessor blinding and one study was at high risk of bias for selective reporting. The interpretation of these studies was limited by diverse outcome measurements, measurement tools, control group techniques, and number and/or times of follow-up. A pooled result from the four studies, including a total of 146 intervention and 135 control participants, indicated uncertain effect in forced expiratory volume in one second (FEV1) % predicted between the disclosure group and the control group (mean difference (MD) 3.43%, 95% confidence interval (CI) -0.61% to 7.47%; very low-quality evidence) at ≤ three months' follow-up. Similarly, evidence from two studies indicated that written emotional disclosure found uncertain effect on forced vital capacity (FVC) (standardised mean difference (SMD) -0.02, 95% CI -0.30 to 0.26; low-quality evidence) and asthma symptoms (SMD -0.22, 95% CI -0.52 to 0.09; low-quality evidence) but may result in improved asthma control at ≤ three months' follow-up (SMD 0.29, 95% CI 0.01 to 0.58; low-quality evidence). We were unable to pool the data for other outcomes. Results from individual trials did not reveal a significant benefit of written emotional disclosure for quality of life, medication use, healthcare utilisation or psychological well-being. Evidence from one trial suggests a significant reduction in beta agonist use (MD -1.62, 95% CI -2.62 to -0.62; low-quality evidence) at ≤ three months' follow-up in the disclosure group compared with controls. The review did not address any adverse effects of emotional writing. Evidence was insufficient to show whether written emotional disclosure compared with writing about non-emotional topics had an effect on the outcomes included in this review. Evidence is insufficient to allow any conclusions as to the role of disclosure in quality of life, psychological well-being, medication use and healthcare utilisation. The evidence presented in this review is generally of low quality. Better designed studies with standardised reporting of outcome measurement instruments are required to determine the effectiveness of written emotional disclosure in the management of asthma.

Four studies, involving 414 participants, were included in this review. The trials lasted between two months and 12 months. One study was conducted in the UK, the other three in the USA. All studies compared emotional disclosure writing versus non-stressful writing. Three studies were conducted in adult participants and one in adolescents. The average age of participants ranged from 14 to 43 years. In all trials, most of the participants were female. There is no evidence to support that written emotional disclosure is helpful in improving lung function or symptoms in patients with asthma. However, disclosure may be beneficial for patients' perceptions of their own asthma control. Based on evidence obtained from the studies, we are not able to draw conclusions about the role of written emotional disclosure in quality of life, psychological well-being, asthma medication use or use of healthcare facilities for asthma-related problems. Better designed studies are necessary to determine the effects of written emotional disclosure for patients with asthma. Our interpretation of the studies was limited by variation in study settings, topics of the non-stressful writing exercise and study duration. The evidence presented in this review is generally of low quality. This summary was current to January 2014.

10.1002/14651858.CD007676.pub2

cochrane-simplification-train-2331

cochrane-simplification-train-2331

We included 22 randomized trials (2130 participants). The mean treatment duration was 2.3 ± 1.3 months (ranging from one to six months). Twenty trials were conducted in China and 18 trials were published in Chinese. Overall, the risk of bias of included trials was high or unclear. Five different herbal medicines were evaluated in the included trials, which compared herbs with conventional medicine in six comparisons (20 trials), or placebo (two trials). There were no outcome data in any of the trials on cardiovascular events and death from any cause. One trial each reported well-being (no significant differences) and economic costs. No serious adverse events were observed. Xuezhikang was the most commonly used herbal formula investigated. A significant effect on total cholesterol (two trial, 254 participants) was shown in favor of Xuezhikang when compared with inositol nicotinate (mean difference (MD) -0.90 mmol/L, 95% confidence interval (CI) -1.13 to -0.68) . Some herbal medicines may have cholesterol-lowering effects. Our findings have to be interpreted with caution due to high or unclear risk of bias of the included trials.

People with hypercholesterolemia have a higher risk of developing coronary artery disease, heart attacks, and stroke. Chinese herbal medicines have been commonly used and studied as cholesterol-lowering agents. To evaluate the effects of various herbal formulations (including single herbs, Chinese proprietary medicines, and mixtures of different herbs) for treating hypercholesterolemia, this review examined 22 randomized controlled trials of five different Chinese herbal medicines. The trials lasted from one to six months (average 2.3 months) and involved 2130 participants. There were no data on cardiovascular events and death from any cause. One trial each reported on well-being (no significant differences) and economic costs . No serious adverse events were observed. The available evidence suggests that several herbal medicines showed some cholesterol-lowering effect. However, due to considerable limitations in the quality of the included trials, further higher-quality and rigorously performed studies are required before any confident conclusions can be reached about the effects of Chinese herbal medicines for hypercholesterolemia.

10.1002/14651858.CD008305.pub2

cochrane-simplification-train-2332

cochrane-simplification-train-2332

We included three randomised controlled trials (RCTs) involving 1358 participants. None of the studies provided useable data for the key outcomes of not having seen a dentist in the past year, not brushing teeth twice a day, chronic pain, clinically important adverse events, and service use. Data for leaving the study early and change in plaque index scores were provided. Oral health education compared with standard care When 'oral health education' was compared with 'standard care', there was no clear difference between the groups for numbers leaving the study early (1 RCT, n = 50, RR 1.67, 95% CI 0.45 to 6.24, moderate-quality evidence), while for dental state: no clinically important change in plaque index, an effect was found. Although this was statistically significant and favoured the intervention group, it is unclear if it was clinically important (1 RCT, n = 40, MD - 0.50 95% CI - 0.62 to - 0.38, very low quality evidence).These limited data may have implications regarding improvement in oral hygiene. Motivational interview + oral health education compared with oral health education Similarly, when 'motivational interview + oral health education' was compared with 'oral health education', there was no clear difference for the outcome of leaving the study early (1 RCT, n = 60 RR 3.00, 95% CI 0.33 to 27.23, moderate-quality evidence), while for dental state: no clinically important change in plaque index, an effect favouring the intervention group was found (1 RCT, n = 56, MD - 0.60 95% CI - 1.02 to - 0.18 very low-quality evidence). These limited, clinically opaque data may or may not have implications regarding improvement in oral hygiene. Monitoring compared with no monitoring For this comparison, only data for leaving the study early were available. We found a difference in numbers leaving early, favouring the 'no monitoring' group (1 RCT, n = 1682, RR 1.07, 95% CI 1.00 to 1.14, moderate-quality evidence). However, these data are problematic. The control denominator is implied and not clear, and follow-up did not depend only on individual participants, but also on professional caregivers and organisations - the latter changing frequently resulting in poor follow-up, but not a good reflection of the acceptability of the monitoring to patients. For this comparison, no data were available for 'no clinically important change in plaque index'. We found no evidence from trials that oral health advice helps people with serious mental illness in terms of clinically meaningful outcomes. It makes sense to follow guidelines and recommendations such as those put forward by the British Society for Disability and Oral Health working group until better evidence is generated. Pioneering trialists have shown that evaluative studies relevant to oral health advice for people with serious mental illness are possible.

We ran an electronic search in November 2015 for trials that randomised people with serious mental illness to receive either oral health advice, monitoring, or standard care. Three studies meeting the required standards were found and are included in this review. Key results The data available in the included trials suggests that participants receiving oral health education had statistically better plaque index scores than those not receiving oral heath education, but what this actually means clinically is unclear. The trials provided no information about such important issues as number of visits made to dentists or how many times teeth were brushed each day and if there were any potential adverse effects of oral health education. The review authors suggest that although there is currently no real evidence available from trials, it would make sense to follow the guidelines and recommendations put forward by the British Society for Disability and Oral Health working group regarding oral health care for people with mental health problems. Quality of the evidence The quality of evidence in the small number of trials available was low to moderate. There is currently a lack of good-quality evidence available from trials to aid in decision-making about the overall effectiveness of oral health advice for people with serious mental illness. More good-quality trials are required to gather better and more concrete evidence. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/

10.1002/14651858.CD008802.pub3

cochrane-simplification-train-2333

cochrane-simplification-train-2333

Eleven studies met the inclusion criteria. Ten studies reported data on patient level: the scan was positive or negative. One study reported on all single lesions (lesion level). The sensitivity of ¹²³I-MIBG (SPECT-CT) scintigraphy (objective 1.1), determined in 608 of 621 eligible patients included in the 11 studies, varied from 67% to 100%. One study, that reported on a lesion level, provided data to calculate the specificity: 68% in 115 lesions in 22 patients. The sensitivity of ¹²³I-MIBG scintigraphy for detecting metastases separately from the primary tumour in patients with all neuroblastoma stages ranged from 79% to 100% in three studies and the specificity ranged from 33% to 89% for two of these studies. One study reported on the diagnostic accuracy of 18F-FDG-PET(-CT) imaging (add-on test) in patients with negative ¹²³I-MIBG scintigraphy (objective 1.2). Two of the 24 eligible patients with proven neuroblastoma had a negative ¹²³I-MIBG scan and a positive 18F-FDG-PET(-CT) scan. The sensitivity of 18F-FDG-PET(-CT) imaging as a single diagnostic test (objective 2.1) and compared to ¹²³I-MIBG (SPECT-CT) (objective 2.2) was only reported in one study. The sensitivity of 18F-FDG-PET(-CT) imaging was 100% versus 92% of ¹²³I-MIBG (SPECT-CT) scintigraphy. We could not calculate the specificity for both modalities. The reported sensitivities of ¹²³-I MIBG scintigraphy for the detection of neuroblastoma and its metastases ranged from 67 to 100% in patients with histologically proven neuroblastoma. Only one study in this review reported on false positive findings. It is important to keep in mind that false positive findings can occur. For example, physiological uptake should be ruled out, by using SPECT-CT scans, although more research is needed before definitive conclusions can be made. As described both in the literature and in this review, in about 10% of the patients with histologically proven neuroblastoma the tumour does not accumulate ¹²³I-MIBG (false negative results). For these patients, it is advisable to perform an additional test for staging and assess response to therapy. Additional tests might for example be 18F-FDG-PET(-CT), but to be certain of its clinical value, more evidence is needed. The diagnostic accuracy of 18F-FDG-PET(-CT) imaging in case of a negative ¹²³I-MIBG scintigraphy could not be calculated, because only very limited data were available. Also the detection of the diagnostic accuracy of index test 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma tumour and its metastases, and to compare this to comparator test ¹²³I-MIBG (SPECT-CT) scintigraphy, could not be calculated because of the limited available data at time of this search. At the start of this project, we did not expect to find only very limited data on specificity. We now consider it would have been more appropriate to use the term "the sensitivity to assess the presence of neuroblastoma" instead of "diagnostic accuracy" for the objectives.

We searched scientific databases for clinical studies comparing ¹²³I-MIBG or 18F-FDG-PET imaging, or both, with microscopic examination of tissue suspected of neuroblastoma (histopathology). The evidence is current up to 11 September 2012. We identified 11 eligible studies including 621 children that fulfilled our inclusion criteria: children < 18 years old with a neuroblastoma and ¹²³I-MIBG or 18F-FDG-PET imaging or both. All studies included proven neuroblastoma. All 11 included studies had methodological limitations. Only one included study provided data on specificity (the ability of a test to correctly classify an individual as 'disease-free') and therefore we could not perform all of the planned analyses. When compared to histopathological results the sensitivity (the ability of a test to correctly classify an individual person as 'diseased') of ¹²³I-MIBG imaging varied from 67% to 100% in patients with histologically proven neuroblastoma. This means that in 100 children with proven neuroblastoma ¹²³I-MIBG imaging will correctly identify 67 to 100 of the neuroblastoma cases. Only one study, that reported on a lesion level, provided data to calculate the specificity (the ability of a test to correctly classify an individual as 'disease-free'): 68% in 115 lesions. This means that of 100 disease-free lesions in patients with proven neuroblastoma ¹²³I-MIBG imaging will correctly identify 68 lesions. So, in about 10% of the cases the neuroblastoma is not visible on ¹²³I-MIBG imaging (false negative results). For these cases, it is advisable to perform an additional test like 18F-FDG-PET imaging, but to be certain of its clinical value, more evidence is needed. Only one included study reported on false positive findings. This means that ¹²³I-MIBG imaging and 18F-FDG-PET imaging incorrectly identified neuroblastoma lesions in patients which might result in wrongly classifying a patient with metastatic disease. It is important to keep in mind that false positive findings can occur, although more research is needed before definitive conclusions can be made. We could not determine the diagnostic accuracy of 18F-FDG-PET imaging, in case the neuroblastoma was incorrectly not identified with ¹²³I-MIBG, due to limited data. Also, we could not calculate the diagnostic accuracy of 18F-FDG-PET imaging for detecting a neuroblastoma and compare this to ¹²³I-MIBG imaging because of the limited available data.

10.1002/14651858.CD009263.pub2

cochrane-simplification-train-2334

cochrane-simplification-train-2334

The previous update (2008) had identified 53 potential studies and included 37 combined for meta-analysis. In this latest update we identified a further 13 studies and included 11, summarizing the results of 50 trials including 4151 participants. Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions: RR 0.86 (95% confidence interval (CI) 0.81 to 0.92; n = 4151) and clinically acceptable intubation conditions (RR 0.97, 95% CI 0.95 to 0.99; n = 3992, 48 trials). A high incidence of detection bias amongst the trials coupled with significant heterogeneity provides moderate-quality evidence for these conclusions, which are unchanged from the previous update. Succinylcholine was more likely to produce excellent intubating conditions when using thiopental as the induction agent: RR 0.81 (95% CI: 0.73 to 0.88; n = 2302, 28 trials). In the previous update, we had concluded that propofol was the superior induction agent with succinylcholine. There were no reported incidences of severe adverse outcomes. We found no statistical difference in intubation conditions when succinylcholine was compared to 1.2 mg/kg rocuronium; however, succinylcholine was clinically superior as it has a shorter duration of action. Succinylcholine created superior intubation conditions to rocuronium in achieving excellent and clinically acceptable intubating conditions.

We included in the review controlled trials from 1966 to February 2015 involving participants of all ages needing rapid intubation using rocuronium and succinylcholine . The minimum dose of rocuronium given was 0.6mg/kg and succinylcholine was 1mg/kg. We have combined the results of 50 trials, with a total of 4151 participants, which compared the effectiveness of succinylcholine versus rocuronium on intubation conditions. No major side effects from use of the drugs were reported. We have found that rocuronium is slightly less effective than succinylcholine for creating excellent and acceptable intubation conditions. Rocuronium should therefore only be used as an alternative to succinylcholine when it is known that succinylcholine should not be used and a more prolonged intubation is expected. The level of evidence is of moderate GRADE due to imperfect study designs and varying techniques used across trials .

10.1002/14651858.CD002788.pub3

cochrane-simplification-train-2335

cochrane-simplification-train-2335

Eleven trials are included in this update; 10 of these we judged to be at an unclear or high risk of bias. The trials were clinically heterogeneous with differences in duration of follow-up, and ultrasound regimens. Nine trials evaluated high frequency ultrasound; seven studies provided data for ulcers healed and two provided data on change in ulcer size only. Two trials evaluated low frequency ultrasound and both reported ulcers healed data. It is uncertain whether high frequency ultrasound affects the proportion of ulcers healed compared with no ultrasound at any of the time points evaluated: at seven to eight weeks (RR 1.21, 95% CI 0.86 to 1.71; 6 trials, 678 participants; low quality evidence - downgraded once for risk of bias and once for imprecision); at 12 weeks (RR 1.26, 95% CI 0.92 to 1.73; 3 trials, 489 participants; moderate quality evidence - downgraded once for imprecision); and at 12 months (RR 0.93, 95% CI 0.73 to 1.18; 1 trial, 337 participants; low quality evidence - downgraded once for unclear risk of bias and once for imprecision). One trial (92 participants) reported that a greater percentage reduction in ulcer area was achieved at four weeks with high-frequency ultrasound, while another (73 participants) reported no clear difference in change in ulcer size at seven weeks. We downgraded the level of this evidence to very low, mainly for risk of bias (typically lack of blinded outcome assessment and attrition) and imprecision. Data from one trial (337 participants) suggest that high frequency ultrasound may increase the risk of non-serious adverse events (RR 1.29, 95% CI 1.02 to 1.64; moderate quality evidence - downgraded once for imprecision) and serious adverse events (RR 1.21, 95% CI 0.78 to 1.89; moderate quality evidence downgraded once for imprecision). It is uncertain whether low frequency ultrasound affects venous ulcer healing at eight and 12 weeks (RR 3.91, 95% CI 0.47 to 32.85; 2 trials, 61 participants; very low quality evidence (downgraded for risk of bias and imprecision)). High-frequency ultrasound probably makes little or no difference to quality of life (moderate quality evidence, downgraded for imprecision). The outcomes of adverse effects, quality of life and cost were not reported for low-frequency ultrasound treatment. It is uncertain whether therapeutic ultrasound (either high or low frequency) improves the healing of venous leg ulcers. We rated most of the evidence as low or very low quality due to risk of bias and imprecision.

In September 2016 we searched for randomised controlled trials (RCTs) that investigated whether ultrasound helps to heal or improves the symptoms of venous leg ulcers. We found 11 trials involving a total of 969 participants. The average (mean) age of participants ranged from 59 years to 70 years. The proportion of female participants ranged from 55% to 79%. Eight studies compared ultrasound with use of no ultrasound for venous leg ulcers and the other three compared ultrasound with sham ultrasound. Seven out of the eleven studies were at high risk of bias and we could not assess the potential bias in three studies due to poor reporting. One study was at low risk of bias. The trials were all different, for example in their duration of follow-up (three weeks to 12 months), and the strength of the ultrasound waves used (high or low frequency ultrasound). It is not clear from this evidence whether ultrasound (high or low frequency) increases the healing of venous leg ulcers. The results of one study (337 participants) suggest that high-frequency ultrasound may be associated with more adverse events such as pain and skin redness (moderate quality evidence). The two studies that evaluated low-frequency ultrasound did not report whether participants experienced side effects. It is also uncertain whether either high- or low-frequency ultrasound affects participants' quality of life. Most of the studies we found did not have many participants, had short follow-up times and had weaknesses of study design that meant they were quite likely to give a misleading result. We consider the available evidence to be low quality due to these risks of bias. This plain language summary is up to date as of September 2016.

10.1002/14651858.CD001180.pub4

cochrane-simplification-train-2336

cochrane-simplification-train-2336

Two studies (n of 80), where n is the number of participants, met the inclusion criteria. Ultrasound to the palmar and dorsal aspects of the hand significantly increased grip strength, measured as weighted mean difference (WMD) from control [WMD 28.07 (95 CI: 13.37 to 42.77)]. Ultrasound to the palmar and dorsal aspects of the hand also appeared to have beneficial effects on the following outcome measures: wrist dorsal flexion [WMD 1.90 (95%CI: 0.64 to 3.16)], duration of morning stiffness [WMD 28.54 (95%CI: 0.18 to 56.90)], number of swollen joints [WMD 1.02 (95%CI: 0.45 to 1.59)], and the number of painful joints [WMD 1.20 (95%CI: 0.45 to 1.95)]. There was no significant difference between a) exercises and wax baths, b) exercises with ultrasound, c) exercises with ultrasound and faradic hand baths on the outcome measures: pain score, grip strength, circumference of proximal interphalangeal (PIP) joints, articular index, and range of motion or level of activity. The reviewers concluded that ultrasound in combination with exercises, faradic current and wax bath treatment modalities is not supported and cannot be recommended. Ultrasound alone can, however, be used on the hand to increase grip strength, and to a lesser extent and based on borderline results, increase wrist dorsal flexion, decrease morning stiffness, reduce the number of swollen joints, and reduce the number of painful joints. It is important to note that these conclusions are limited by methodological considerations such as poor quality of the included trials, the low number of clinical trials, and the small number of study participants.

This review of two randomized trials (RCTs) showed that continuous ultrasound applied in water to the dorsal and palmar aspects of the hand increased grip strength as compared with placebo. This benefit was not evident with combined therapy (exercise, wax bath, faradic hand baths). Ultrasound also produced a borderline increase in wrist dorsal flexion, decreased morning stiffness, and reduced the number of swollen and painful joints. The conclusions are limited by few studies, small sample size and limitations in study methodology.

10.1002/14651858.CD003787

cochrane-simplification-train-2337

cochrane-simplification-train-2337

We included 21 RCTs (2082 women). The included trials mostly assessed the levonorgestrel-releasing intrauterine device (LNG IUS) (no conclusions could be reached from one small study assessing Progestasert which was discontinued in 2001) and so conclusions are based only on LNG IUS. Comparisons were made with placebo, oral medical treatment, endometrial destruction techniques and hysterectomy. Ratings for the overall quality of the evidence for each comparison ranged from very low to high. Limitations in the evidence included inadequate reporting of study methods and inconsistency. Seven studies compared the LNG IUS with oral medical therapy: either norethisterone acetate (NET) administered over most of the menstrual cycle, medroxyprogesterone acetate (MPA) (administered for 10 days), the oral contraceptive pill, mefenamic acid or usual medical treatment where participants could choose the oral treatment that was most suitable. The LNG IUS was more effective at reducing HMB as measured by the alkaline haematin method (MD 66.91 mL, 95% CI 42.61 to 91.20; two studies, 170 women; I2 = 81%, low quality evidence) or by Pictorial Bleeding Assessment Chart (PBAC) scores (MD 55.05, 95% CI 27.83 to 82.28; three studies, 335 women; I2 = 79%, low quality evidence), improving quality of life and a greater number of women continued with their treatment at two years when compared with oral treatment. Although substantial heterogeneity was identified for the bleeding outcomes, the direction of effect consistently favoured the LNG IUS. There was insufficient evidence to reach conclusions on satisfaction. Minor adverse effects (such as pelvic pain, breast tenderness and ovarian cysts) were more common with the LNG IUS. Ten studies compared the LNG IUS with endometrial destruction techniques: three with transcervical resection, one with rollerball ablation and six with thermal balloon ablation. Evidence was inconsistent and very low quality with respect to reduction in bleeding outcomes and satisfaction was comparable between treatments (low and moderate quality evidence). Improvements in quality of life were experienced with both types of treatment. Minor adverse events were more common with the LNG IUS overall, but it appeared more cost effective compared to thermal ablation within a two-year time frame in one study. Three studies compared the LNG IUS with hysterectomy. The LNG IUS was not as successful at reducing HMB as hysterectomy (high quality evidence). The women in these studies reported improved quality of life, regardless of treatment. In spite of the high rate of surgical treatment in those having LNG IUS within 10 years, the LNG IUS was more cost effective than hysterectomy. The levonorgestrel-releasing intrauterine device (LNG IUS) is more effective than oral medication as a treatment for heavy menstrual bleeding (HMB). It is associated with a greater reduction in HMB, improved quality of life and appears to be more acceptable long term but is associated with more minor adverse effects than oral therapy. When compared to endometrial ablation, it is not clear whether the LNG IUS offers any benefits with regard to reduced HMB and satisfaction rates and quality of life measures were similar. Some minor adverse effects were more common with the LNG IUS but it appeared to be more cost effective than endometrial ablation techniques. The LNG IUS was less effective than hysterectomy in reducing HMB. Both treatments improved quality of life but the LNG IUS appeared more cost effective than hysterectomy for up to 10 years after treatment.

This review contains 21 RCTs conducted up to July 2014 that included 2082 participants with heavy menstrual bleeding. Evidence obtained is current to January 2015. Almost all the studies assessed the effects of the LNG IUS and conclusions refer only to this device. The LNG IUS was more effective in reducing heavy menstrual bleeding and improving quality of life than oral medication. Satisfaction with treatment was not assessed in enough trials to know whether this was better with LNG IUS. The evidence suggested that the LNG IUS and techniques used to remove the inner lining of the womb were similarly effective at reducing heavy menstrual bleeding and improving quality of life and satisfaction and the two treatments had similar failure rates. The LNG IUS caused higher rates of some side effects, such as breast tenderness, bloating, weight gain and ovarian cysts, but this did not seem to cause women to stop taking their treatment. The LNG IUS was not as effective as hysterectomy in reducing menstrual blood loss but improvements in quality of life were similar. Although many women trying the LNG IUS eventually went on to have a hysterectomy for their heavy menstrual bleeding, the LNG IUS appeared to have lower overall costs than either endometrial ablation or hysterectomy. Many of the trials in this review were small (<100 participants) and some were at high risk of bias. Ratings for the overall quality of the evidence for each comparison ranged from very low to high. Limitations in the evidence included inadequate reporting of study methods and inconsistency. One large trial compared the LNG IUS with hysterectomy over a 10-year period and a number of other trials made assessments two years after starting treatment, so we have some information on the long-term effects of treatments. Future research needs to measure satisfaction.

10.1002/14651858.CD002126.pub3

cochrane-simplification-train-2338

cochrane-simplification-train-2338

In the original 2010 review, we identified no relevant studies. This updated review included one RCT involving 245 participants that compared abdominal paracentesis and intraperitoneal infusion of catumaxomab versus abdominal paracentesis alone. The study was at high risk of bias in almost all domains. The data were not suitable for analysis. The median time to the first deterioration of QoL ranged from 19 to 26 days in participants receiving paracentesis alone compared to 47 to 49 days among participants receiving paracentesis with catumaxomab infusion (very low-certainty evidence). Adverse events were only reported among participants receiving catumaxomab infusion. The most common severe adverse events were abdominal pain and lymphopenia (157 participants; very low-certainty evidence). There were no data on the improvement of symptoms, satisfaction of participants and caregivers, and cost-effectiveness. Currently, there is insufficient evidence to recommend the most appropriate management of drainage for malignant ascites among women with gynaecological cancer, as there was only very low-certainty evidence from one small RCT at overall high risk of bias.

We searched for studies up to Novemeber 2019 that compared different ways of managing the drainage of fluid collected in the abdomen of women with gynaecological cancer (cancer that starts in a woman's reproductive organs). The original 2010 review found no relevant studies. This updated review included one randomised controlled trial (RCT: a type of study in which people are randomly assigned to receive different treatments) involving 245 women that compared drainage combined with catumaxomab (a medicine used to treatment malignant ascites) versus drainage alone. However, the results were insufficient to assess the difference between these treatments. Although women receiving drainage combined with catumaxomab had better quality of life (the general well-being of a person) for longer compared to drainage alone, we are very unsure of this evidence due to the small number of participants and trials. There were some side effects in the drainage plus catumaxomab group (e.g. pain, low white blood cell count), but they were not well reported. At present, there is insufficient data regarding the best management of drainage for malignant ascites among women with gynaecological cancer. The evidence is current to 4 November 2019.

10.1002/14651858.CD007794.pub3

cochrane-simplification-train-2339

cochrane-simplification-train-2339

We included 22 trials involving 9753 participants. In participants with symptomatic carotid stenosis, compared with endarterectomy stenting was associated with a higher risk of periprocedural death or stroke (the primary safety outcome; OR 1.70, 95% CI 1.31 to 2.19; P < 0.0001, I² = 5%; 10 trials, 5396 participants; high-certainty evidence); and periprocedural death, stroke, or myocardial infarction (OR 1.43, 95% CI 1.14 to 1.80; P = 0.002, I² = 0%; 6 trials, 4861 participants; high-certainty evidence). The OR for the primary safety outcome was 1.11 (95% CI 0.74 to 1.64) in participants under 70 years old and 2.23 (95% CI 1.61 to 3.08) in participants 70 years old or more (interaction P = 0.007). There was a non-significant increase in periprocedural death or major or disabling stroke with stenting (OR 1.36, 95% CI 0.97 to 1.91; P = 0.08, I² = 0%; 7 trials, 4983 participants; high-certainty evidence). Compared with endarterectomy, stenting was associated with lower risks of myocardial infarction (OR 0.47, 95% CI 0.24 to 0.94; P = 0.03, I² = 0%), cranial nerve palsy (OR 0.09, 95% CI 0.06 to 0.16; P < 0.00001, I² = 0%), and access site haematoma (OR 0.32, 95% CI 0.15 to 0.68; P = 0.003, I² = 27%). The combination of periprocedural death or stroke or ipsilateral stroke during follow-up (the primary combined safety and efficacy outcome) favoured endarterectomy (OR 1.51, 95% CI 1.24 to 1.85; P < 0.0001, I² = 0%; 8 trials, 5080 participants; high-certainty evidence). The rate of ipsilateral stroke after the periprocedural period did not differ between treatments (OR 1.05, 95% CI 0.75 to 1.47; P = 0.77, I² = 0%). In participants with asymptomatic carotid stenosis, there was a non-significant increase in periprocedural death or stroke with stenting compared with endarterectomy (OR 1.72, 95% CI 1.00 to 2.97; P = 0.05, I² = 0%; 7 trials, 3378 participants; moderate-certainty evidence). The risk of periprocedural death or stroke or ipsilateral stroke during follow-up did not differ significantly between treatments (OR 1.27, 95% CI 0.87 to 1.84; P = 0.22, I² = 0%; 6 trials, 3315 participants; moderate-certainty evidence). Moderate or higher carotid artery restenosis (50% or greater) or occlusion during follow-up was more common after stenting (OR 2.00, 95% CI 1.12 to 3.60; P = 0.02, I² = 44%), but the difference in risk of severe restenosis was not significant (70% or greater; OR 1.26, 95% CI 0.79 to 2.00; P = 0.33, I² = 58%; low-certainty evidence). Stenting for symptomatic carotid stenosis is associated with a higher risk of periprocedural stroke or death than endarterectomy. This extra risk is mostly attributed to an increase in minor, non-disabling strokes occurring in people older than 70 years. Beyond the periprocedural period, carotid stenting is as effective in preventing recurrent stroke as endarterectomy. However, combining procedural safety and long-term efficacy in preventing recurrent stroke still favours endarterectomy. In people with asymptomatic carotid stenosis, there may be a small increase in the risk of periprocedural stroke or death with stenting compared with endarterectomy. However, CIs of treatment effects were wide and further data from randomised trials in people with asymptomatic stenosis are needed.

We examined evidence about benefits and risks from studies that compared carotid artery stenting to carotid surgery in people who already had symptoms caused by carotid stenosis (stroke, transient ischaemic attack (TIA), or ocular (eye) symptoms) or in people who have never experienced symptoms. The studies had to be randomised; that is, the decision whether people were treated by stenting or surgery had to be made randomly and neither they nor the researchers were able to decide which treatment they received. This was to make the comparison as unbiased, or fair, as possible. We searched for studies up to August 2018. We assessed the quality of all the studies we included. This review included 22 studies involving 9753 participants. In people who have already experienced symptoms from a narrowing in the carotid artery, stenting caused more strokes or deaths around the time of the procedure than surgery. This was especially true for people over the age of 70 years. After the initial procedure, both treatments were equally effective in preventing stroke or death in the long term. In people who had never experienced symptoms from the carotid stenosis, both carotid artery stenting and surgery carried a similar risk of stroke or death in the short and long term, although the certainty of the evidence in these people was only moderate and the results should be interpreted with caution. In general, the quality of the evidence was high. The main factor reducing our confidence in the evidence was in studies comparing both treatments in people who had never experienced symptoms from the narrowing in the carotid artery. For these people, more studies are needed to draw firm conclusions about the risks and benefits of stenting compared to surgery.

10.1002/14651858.CD000515.pub5

cochrane-simplification-train-2340

cochrane-simplification-train-2340

We included two RCTs and four CRCTs involving 352 physicians, 48 residents, and 135 allied health practitioners. Overall risk of bias was low as was quality of the evidence. One comparison was supported by three studies and three comparisons were supported by single studies, but outcomes across the three studies were highly heterogeneous. We found no studies to support EHI versus no alternative. Given these factors, it was not possible to determine the relative effectiveness of interventions. All studies reported practitioner use of EHI, two reported on compliance with electronic practice guidelines, and none reported on patient outcomes. One trial (139 participants) measured guideline adherence for an electronic versus printed guideline, but reported no difference between groups (median OR 0.85, IQR 0.74 to 1.08). One small cross-over trial (10 participants) reported increased use of clinical guidelines when provided with a mobile versus stationary, desktop computer (mean use per shift: intervention group (IG) 3.6, standard deviation (SD) 1.7 vs. control group (CG) 2.0 (SD 1.9), P value = 0.033). One cross-over trial (203 participants) reported that using a customized versus a generic interface had little impact on practitioners' use of EHI (mean difference in adjusted end-of-study rate: 0.77 logins/month/user, 95% confidence interval (CI) CI 0.43 to 1.11). Three trials included education or training and reported increased use of EHI by practitioners following training. This review provided no evidence that the use of EHI translates into improved clinical practice or patient outcomes, though it does suggest that when practitioners are provided with EHI and education or training, the use of EHI increases. We have defined use as the activity of logging into an EHI resource, but based on our findings use does not automatically translate to the application of EHI in practice. While using EHI may be an important component of evidence-based medicine, alone it is insufficient to improve patient care or clinical practices. For EHI to be applied in patient care, it will be necessary to understand why practitioners' are reluctant to apply EHI when treating people, and to determine the most effective way(s) to reduce this reluctance.

We found six studies involving 535 healthcare practitioners. The studies examined strategies encouraging practitioners to use EHI when caring for patients. We measured practitioners' use of EHI by counting the number of times they logged onto it; by measuring whether or not practitioners' followed the guidance provided by EHI; and by improvements experienced by patients. The studies compared the following strategies: EHI versus printed information (one study); EHI on a "mobile" (e.g. laptop computer) versus a stationary, desktop computer (one study); EHI presented with different search interfaces (an interface is what a user sees when accessing an online resource, think of Google versus Yahoo) (one study); and EHI provided with training (three studies). The results of this review showed that when provided with a combination of EHI and training, practitioners used the information more often. Two studies measured doctors' use of electronic treatment guidelines, but showed that the electronic aspect of the guidelines did not mean that doctors followed the guidelines. This review provided no information on whether more frequent use of EHI translated into improved clinical practice or whether patients were better off when doctors or nurses used health information when treating them. All included studies were randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups), which are considered high-quality sources of evidence. However, three of the four comparisons that we examined were supported by only one study each and single studies do not typically produce high-quality evidence. Overall, we rate the body of evidence in this review as low quality.

10.1002/14651858.CD004749.pub3

cochrane-simplification-train-2341

cochrane-simplification-train-2341

We included six RCTs (one with a cross-over design) randomising 310 children and reporting outcomes for 297 children. Most participants were aged under seven months with only two participants aged over one year (seven and 12 years old); where specified, 60% were boys. In two studies, condition severity was mild to moderate; one study included two participants with severe ISD; the other studies did not describe baseline severity or described it as body surface area affected. The study setting was not always clear but likely a paediatric outpatient clinic in the following countries: Thailand, Israel, USA, France, and Australia. Two studies compared oral biotin (a B group vitamin) against placebo, two studies compared proprietary products against placebo cream or a control shampoo, and two studies compared topical corticosteroids against other products. The studies were generally short-term, between 10 and 42 days' duration; only one study followed the participants until resolution of the rash or eight months of age. We assessed the risk of bias as unclear for most aspects due to lack of reporting, but two of the studies were at high risk of performance and detection bias due to the appearance of the intervention, the trial design (open-label), or use of overlabelled tubes. Two trials had a high risk of attrition bias. All the results given below were based on very low-quality evidence. Treatment duration ranged from one week to three weeks. For the two trials comparing biotin versus placebo (n = 35), one did not report a measure of change in severity (only change in duration of rash) while the other did not report raw data (only 'no statistically significant difference'), measured at three weeks. Neither trial reported on adverse events. Two trials compared proprietary products against placebo (n = 160). One trial assessed change in severity via percentage success (96% of participants in non-steroidal cream Promiseb versus 92% in placebo), and reported no adverse events (both assessed at day 14). The other trial assessed change in severity via reduction in lesional score (surface area covered), finding better results for lactamide MEA gel (a moisturising agent) plus shampoo (81.4%) compared with shampoo only (70.2%; P = 0.0092). No adverse events were described, but signs of discomfort were similar in both groups (both assessed at day 21). In the comparison of topical steroids versus another product, change in severity was measured through evaluation of cure and body surface (n = 102). In one trial comparing hydrocortisone 1% lotion with licochalcone 0.025% lotion, there was no significant difference in participants cured (95.8% with hydrocortisone compared to 97.1% with licochalcone). One person in the licochalcone group developed more erythema, but there were no other adverse events (both outcomes assessed at day 14). In the trial comparing flumethasone pivalate 0.02% ointment versus eosin 2% aqueous solution, a reduction in body surface area affected was seen in both groups at day 10 (9% with corticosteroid versus 7% with aqueous solution), with all infants showing less than 10% involvement. There were no adverse events (both outcomes assessed at day 10). No studies measured QoL. We found no trials testing commonly used treatments such as mineral oils, salicylic acid, or antifungals. Our review identified only a limited number of studies investigating the effects of interventions for ISD in infants and young children. Unlike the reviews investigating the effects of treatments in adults, our results showed that there is uncertainty regarding the effectiveness and safety of studied treatments due to the very low-certainty evidence for all comparisons and outcomes. We assessed most bias domains as at unclear risk, but there was a high risk of bias for (mainly) performance, attrition, and detection bias. Evidence was limited further by imprecision (small studies, low number of events), indirectness (mainly with the outcomes assessed), and poor trial reporting. In most studies, the prognosis for the condition was favourable regardless of intervention but interpretation is limited by the very low-certainty evidence. Further research is needed with large, well-conducted, and well-reported intervention trials, particularly of interventions commonly recommended or used, such as emollients or shampoos and brushing, antifungals, or steroids. All studies should report standardised and validated relevant outcome measures, including adverse events, severity, and QoL, and they should be conducted in primary care settings where the majority of ISD is managed. Future trials should compare against placebo, no treatment, or standard care.

We included six studies which were small with 310 infants, of whom 297 were included for analysis. The studies were short (10 to 42 days), and generally poor quality. Studies were in different countries, and, where stated, in paediatric clinics. Where stated in three studies, 60% were boys (144 boys among 241 infants). Most infants were aged under seven months; two were aged seven and 12 years. ISD severity where described was mild to moderate; one study included two participants with severe ISD. The treatments tested included: oral biotin (a B group vitamin) compared to placebo; trademarked creams or gels compared to placebo (or a control group); and steroid lotion or ointment compared to licochalcone (Chinese liquorice) cream and eosin (a red staining agent). Four studies had support from pharmaceutical companies: in three studies, a company supplied the intervention product; a company assisted with statistical analysis in one study; one employed a study author; and one had authors who were consultants to the pharmaceutical company. The evidence is current to 22 May 2018. Two trials assessed oral biotin versus placebo. One study only assessed duration of rash, and the other only reported that there was no differences between groups. Thus, it was unclear which treatment was more effective. In the two trials assessing trademarked skin products versus placebo, there was similar improvement in severity between Promiseb cream (96%) and placebo (92%). One trial assessed lactamide MEA gel plus shampoo versus shampoo only. Reduction of surface area covered and severity of rash was slightly higher in the gel group (81.4%) compared with shampoo only (70.2%). When comparing hydrocortisone 1% lotion with licochalcone 0.025% lotion in one study, cure rates, as a sign of severity, were also similar (95.8% with hydrocortisone versus 97.1% with licochalcone). Reduction in body surface area affected was similar when comparing flumethasone pivalate 0.02% ointment (9%) versus eosin 2% aqueous solution (7%). Only two trials reported side effects, including one case of increased skin redness with licochalcone, while in the study comparing lactamide MEA gel plus shampoo versus shampoo only there were no specific side effects reported. No studies measured improvement in quality of life. The quality of the evidence was downgraded to very low for all outcome measures in this review due to serious concerns with how the studies were conducted (risk of bias), how the outcomes were measured and reported, differences between the assessed treatments, and the small number of participants included. Thus, we cannot be certain of their accuracy.

10.1002/14651858.CD011380.pub2

cochrane-simplification-train-2342

cochrane-simplification-train-2342

We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the insulin analogue, insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of short acting insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

We found nine randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) comparing the insulin analogues, insulin lispro and insulin aspart, to regular human insulin delivered to 2693 participants. The people in the included studies were monitored (called follow-up) for between 24 and 52 weeks. This evidence is up-to-date as of 15 April 2015. According to our analysis, short-acting insulin analogues were slightly better than regular human insulin regarding long-term glycaemic control (where blood glucose is at controlled levels) and showed similar episodes of low blood sugar (called hypoglycaemia), especially with regard to severe (night-time) hypoglycaemia. We found no information on late diabetes complications such as problems with the eyes, kidneys or feet. The studies did not report costs and they were too short to investigate death from any cause reliably. We also found no clear evidence for a marked effect of insulin analogues on the health-related quality of life (which is physical, mental, emotional and social health). The quality of the included studies was low or very low, mainly because none of the studies was carried out in a blinded way (where healthcare professionals and participants do not know which treatment they received) so that risk of bias, especially for outcomes such as hypoglycaemic episodes, was present in all of the studies. Furthermore, several studies showed inconsistencies in the reporting of methods and results.

10.1002/14651858.CD012161

cochrane-simplification-train-2343

cochrane-simplification-train-2343

We included six trials, with a total of 748 women in this review. All trials included women in whom there was no overriding indication for immediate delivery in the fetal or maternal interest. Half of the trials were at low risk of bias for methods of randomisation and allocation concealment; and four trials were at low risk for selective reporting. For most other domains, risk of bias was unclear. There were insufficient data for reliable conclusions about the comparative effects on most outcomes for the mother. Two studies reported on maternal deaths; neither study reported any deaths (two studies; 320 women; low-quality evidence). It was uncertain whether interventionist care reduced eclampsia (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.06 to 15.58; two studies; 359 women) or pulmonary oedema (RR 0.45, 95% CI 0.07 to 3.00; two studies; 415 women), because the quality of the evidence for these outcomes was very low. Evidence from two studies suggested little or no clear difference between the interventionist and expectant care groups for HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome (RR 1.09, 95% CI 0.62 to 1.91; two studies; 359 women; low-quality evidence). No study reported on stroke. With the addition of data from two studies for this update, there was now evidence to suggest that interventionist care probably made little or no difference to the incidence of caesarean section (average RR 1.01, 95% CI 0.91 to 1.12; six studies; 745 women; Heterogeneity: Tau² = 0.01; I² = 63%). For the baby, there was insufficient evidence to draw reliable conclusions about the effects on perinatal deaths (RR 1.11, 95% CI 0.62 to 1.99; three studies; 343 women; low-quality evidence). Babies whose mothers had been allocated to the interventionist group had more intraventricular haemorrhage (RR 1.94, 95% CI 1.15 to 3.29; two studies; 537 women; moderate-quality evidence), more respiratory distress caused by hyaline membrane disease (RR 2.30, 95% CI 1.39 to 3.81; two studies; 133 women), required more ventilation (RR 1.50, 95% CI 1.11 to 2.02; two studies; 300 women), and were more likely to have a lower gestation at birth (mean difference (MD) -9.91 days, 95% CI -16.37 to -3.45 days; four studies; 425 women; Heterogeneity: Tau² = 31.74; I² = 76%). However, babies whose mothers had been allocated to the interventionist group were no more likely to be admitted to neonatal intensive care (average RR 1.19, 95% CI 0.89 to 1.60; three studies; 400 infants; Heterogeneity: Tau² = 0.05; I² = 84%). Babies born to mothers in the interventionist groups were more likely to have a longer stay in the neonatal intensive care unit (MD 7.38 days, 95% CI -0.45 to 15.20 days; three studies; 400 women; Heterogeneity: Tau² = 40.93, I² = 85%) and were less likely to be small-for-gestational age (RR 0.38, 95% CI 0.24 to 0.61; three studies; 400 women). There were no clear differences between the two strategies for any other outcomes. This review suggested that an expectant approach to the management of women with severe early onset pre-eclampsia may be associated with decreased morbidity for the baby. However, this evidence was based on data from only six trials. Further large, high-quality trials are needed to confirm or refute these findings, and establish if this approach is safe for the mother.

We searched for evidence in November 2017 and identified six randomised trials. This review included six trials that randomly assigned women to a policy of interventionist management or expectant management when presenting with severe pre-eclampsia before 34 weeks of pregnancy. A total of 748 women were included in these six trials. Babies born to women allocated to an interventionist approach were probably more likely to experience adverse effects such as bleeding in the brain (intraventricular haemorrhage). They may also have been more likely to require ventilation, have a longer stay in the neonatal unit, have a lower gestation at birth in days, and weigh less at birth than those babies born to women allocated to an expectant management approach. There was insufficient evidence for reliable conclusions about the effects on perinatal deaths. Babies whose mothers had been allocated to the interventionist group were no more likely to be admitted to neonatal intensive care. There were no maternal deaths in the two studies that reported this outcome. The evidence was very low-quality for the outcome of fits or convulsions (eclampsia), or of fluid in the lungs (pulmonary oedema), and so it was uncertain whether interventionist care made any clear difference to the mothers' health. Evidence from two studies suggested little or no clear difference between the interventionist and expectant care groups for a severe form of pre-eclampsia, which affects the liver and blood clotting, called HELLP syndrome, which stands for haemolysis (breakdown of red blood cells), elevated liver enzymes (a sign of liver damage), and low platelets (platelets help the blood to clot). None of the studies reported on the incidence of stroke in the mother. With the addition of data from two studies for this update, there was now evidence to suggest that interventionist care probably made little or no difference to the caesarean section rate. In the absence of an over-riding maternal or fetal indication for immediate delivery, delay may be more beneficial for the baby. However, there were insufficient data to enable us to draw reliable conclusions about the comparative effects on most outcomes for the mother, and hence the maternal safety of an expectant approach. This evidence was based on data from only six trials. Further large trials with long-term follow-up of the children are needed to confirm or refute whether expectant care is better than early delivery for women who suffer from severe pre-eclampsia before 34 weeks of pregnancy.

10.1002/14651858.CD003106.pub3

cochrane-simplification-train-2344

cochrane-simplification-train-2344

We identified 14 RCTs with 2422 eligible patients. For eight RCTs with 1049 patients (43.3%), we were able to obtain IPD. Perioperative chemotherapy was associated with significantly longer overall survival (hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.73 to 0.89). This corresponds to a relative survival increase of 19% or an absolute survival increase of 9% at five years. This survival advantage was consistent across most subgroups. There was a trend towards a more pronounced treatment effect for tumors of the GE junction compared to other sites, and for combined chemoradiotherapy as compared to chemotherapy in tumors of the esophagus and GE junction. Resection with negative margins was a strong predictor of survival. Multivariable analysis showed that tumor site, performance status, and age have an independent significant effect on survival. Moreover, there was a significant interaction of the effect of perioperative chemotherapy with age (larger treatment effect in younger patients). Perioperative chemotherapy also showed a significant effect on several secondary outcomes. It was associated with longer disease-free survival, higher rates of R0 resection, and more favorable tumor stage upon resection, while there was no association with perioperative morbidity and mortality. Perioperative chemotherapy for resectable gastroesophageal adenocarcinoma increases survival compared to surgery alone. It should thus be offered to all eligible patients. There is a trend to a larger survival advantage for tumors of the GE junction as compared to other sites and for chemoradiotherapy as compared to chemotherapy in esophageal and GE junction tumors. Likewise, there is an interaction between age and treatment effect, with younger patients having a larger survival advantage, and no survival advantage for elderly patients.

This systematic review uses the data of individual patients from eight and published data from another six randomized controlled trials. We found that the administration of chemotherapy before surgery leads to longer survival in patients with adenocarcinoma of the esophagus, the junction between esophagus and stomach, and the stomach. The findings suggest that patients whose tumor is in the junction between esophagus and stomach and younger patients benefit most from the chemotherapy. Moreover, the addition of radiation to the chemotherapy seems to yield an additional advantage to patients, at least in tumors of the esophagus and the junction between esophagus and stomach. Chemotherapy before surgery does not increase the risk of suffering a complication during or after surgery.

10.1002/14651858.CD008107.pub2

cochrane-simplification-train-2345

cochrane-simplification-train-2345

We included 68 systematic reviews published in the Cochrane Library up to May 2018. All were of high quality. These reviews identified 38 interventions that were effective (n = 23) or promising (n = 15), and they identified 19 interventions that were ineffective (n = 2) or possibly ineffective (n = 17). For 15 interventions, review authors were unable to draw conclusions owing to lack of evidence. We identified an additional 11 protocols and four titles for future inclusion in this overview. This overview provides the most up-to-date evidence on ART cycles from systematic reviews of randomised controlled trials. Fertility treatments are costly, and the stakes are high. Using the best available evidence to optimise outcomes is best practice. Evidence from this overview could be used to develop clinical practice guidelines and protocols that can be applied in daily clinical practice to improve live birth rates and reduce rates of multiple pregnancy, cycle cancellation, and ovarian hyperstimulation syndrome.

We included 68 Cochrane systematic reviews on various stages of the ART cycle. All were of high quality. We included in the overview reviews of in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). We did not include reviews of intrauterine insemination (placing sperm inside a woman's uterus to facilitate fertilisation) or ovulation induction (stimulation of ovulation by medication). This overview provides the most up-to-date evidence from randomised controlled trials on ART cycles. The overview is up-to-date to May 2018. The reviews identified 38 interventions that were effective (n = 23) or promising (n = 15), and they identified 19 interventions that were ineffective (n = 2) or possibly ineffective (n = 17). For 15 interventions, the reviews were unable to draw conclusions owing to lack of evidence. Use of evidence from this overview to guide clinical practice should help to improve live birth rates and reduce rates of multiple pregnancy, cycle cancellation, and ovarian hyperstimulation syndrome. All included reviews were of high quality. The quality of the evidence for specific comparisons ranged from very low to high.

10.1002/14651858.CD010537.pub5

cochrane-simplification-train-2346

cochrane-simplification-train-2346

We included 34 trials (16 trials of cessation; nine trials of reduction; one trial of relapse prevention; eight trials that reported smoking outcomes for interventions aimed at other purposes). Seven trials compared bupropion with placebo; meta-analysis showed that cessation rates after bupropion were significantly higher than placebo at the end of treatment (seven trials, N = 340; risk ratio [RR] 3.03; 95% confidence interval [CI] 1.69 to 5.42) and after six months (five trials, N = 214, RR 2.78; 95% CI 1.02 to 7.58). There were no significant differences in positive, negative and depressive symptoms between bupropion and placebo groups. There were no reports of major adverse events such as seizures with bupropion. Smoking cessation rates after varenicline were significantly higher than placebo, at the end of treatment (2 trials, N = 137; RR 4.74, 95% CI 1.34 to 16.71). Only one trial reported follow-up at six months and the CIs were too wide to provide evidence of a sustained effect (one trial, N = 128, RR 5.06, 95% CI 0.67 to 38.24). There were no significant differences in psychiatric symptoms between the varenicline and placebo groups. Nevertheless, there were reports of suicidal ideation and behaviours from two people on varenicline. Two studies reported that contingent reinforcement (CR) with money may increase smoking abstinence rates and reduce the level of smoking in patients with schizophrenia. However, it is uncertain whether these benefits can be maintained in the longer term. There was no evidence of benefit for the few trials of other pharmacological therapies (including nicotine replacement therapy (NRT)) and psychosocial interventions in helping smokers with schizophrenia to quit or reduce smoking. Bupropion increases smoking abstinence rates in smokers with schizophrenia, without jeopardizing their mental state. Varenicline may also improve smoking cessation rates in schizophrenia, but its possible psychiatric adverse effects cannot be ruled out. CR may help this group of patients to quit and reduce smoking in the short term. We failed to find convincing evidence that other interventions have a beneficial effect on smoking in schizophrenia.

In this review, we analysed studies which investigated a wide variety of interventions. Our results suggested that bupropion (an antidepressant medication previously shown to be effective for smoking cessation) helps patients with schizophrenia to quit smoking. The effect was clear at the end of the treatment and it may also be maintained after six months. Patients who used bupropion in the trials did not experience any major adverse effect and their mental state was stable during the treatment. Another medication, varenicline (a nicotine partial agonist which has been shown to be an effective intervention for smoking cessation in smokers without schizophrenia), also helps individuals with schizophrenia to quit smoking at the end of the treatment. However, this evidence is only based on two studies. We did not have sufficient direct evidence to know whether the benefit of varenicline is maintained for six months or more. In addition, there has been ongoing concern of potential psychiatric adverse events including suicidal ideas and behaviour among smokers who use varenicline. We found that two patients, among 144 who used varenicline, had either suicidal ideas or behaviour. Smokers with schizophrenia who receive money as a reward for quitting may have a higher rate of stopping smoking whilst they get payments. However, there is no evidence that they will remain abstinent after the reward stops. There was too little evidence to show whether other treatments like nicotine replacement therapy and psychosocial interventions are helpful.

10.1002/14651858.CD007253.pub3

cochrane-simplification-train-2347

cochrane-simplification-train-2347

A systematic search of all available databases and other sources failed to identify any completed randomized, double-blind and placebo-controlled trials, assessing the efficacy of ibuprofen in AD eligible for inclusion in the review. One double-blind placebo-controlled trial investigating ibuprofen treatment for age-associated memory impairment has been identified, but is yet unfinished and no data are yet available. Other trials assessing the effect of ibuprofen on CSF beta amyloid in cognitively unimpaired individuals and the effect of other NSAIDs such as naproxen and rofecoxib for people with AD are currently underway. No evidence yet exists from randomized double-blind and placebo-controlled trials on whether ibuprofen is efficacious for patients diagnosed as having Alzheimer's disease. Ibuprofen, like other NSAIDs, has an identifiable and in some instances a significant side-effect profile which may include gastrointestinal bleeding. Therefore, it needs to be shown that the benefits of such a treatment outweighs the risk of side effects before ibuprofen can be recommended for people with Alzheimer's disease.

Animal and cell culture studies have produced evidence that inflammatory processes may be involved in the pathogenesis of AD. As a result, agents such as ibuprofen have been proposed for the treatment of people with AD. Although ibuprofen is better tolerated overall than some other NSAIDs, such as indomethacin, no randomized controlled trials investigating the efficacy of this drug for treatment of people with AD have been published. One such a trial is underway. The use of ibuprofen for the treatment of AD cannot at present be recommended.

10.1002/14651858.CD004031

cochrane-simplification-train-2348

cochrane-simplification-train-2348

Six studies were identified that randomised 596 live kidney donors to either LDN or ODN arms. All studies were assessed as having low or unclear risk of bias for selection bias, allocation bias, incomplete outcome data and selective reporting bias. Four of six studies had high risk of bias for blinding. Various different combinations of techniques were used in each study, resulting in heterogeneity in the results. The conversion rate from LDN to ODN ranged from 1% to 1.8%. LDN was generally found to be associated with reduced analgesia use, shorter hospital stay, and faster return to normal physical functioning. The extracted kidney was exposed to longer warm ischaemia periods (2 to 17 minutes) with no associated short-term consequences. ODN was associated with shorter duration of procedure. For those outcomes that could be meta-analysed there were no significant differences between LDN or ODN for perioperative complications (RR 0.87, 95% CI 0.47 to 4.59), reoperations (RR 0.57, 95% CI 0.09 to 3.64), early graft loss (RR 0.31, 95% CI 0.06 to 1.48), delayed graft function (RR 1.09, 95% CI 0.52 to 2.30), acute rejection (RR 1.41, 95 % CI 0.87 to 2.27), ureteric complications (RR 1.51, 95% CI 0.69 to 3.31), kidney function at one year (SMD 0.15, 95% CI -0.11 to 0.41) or graft loss at one year (RR 0.76, 95% CI 0.15 to 3.85). LDN is associated with less pain compared with open surgery; however, there are equivalent numbers of complications and occurrences of perioperative events that require further intervention. Kidneys obtained using LDN procedures were exposed to longer warm ischaemia periods than ODN-acquired grafts, although this has not been reported as being associated with short-term consequences.

Six studies randomising 596 healthy kidney donors to either keyhole or open surgery, found keyhole surgery to be associated with less pain for the donor but had similar numbers of complications that can require further treatment or surgery or both. Donor kidneys that were obtained using the keyhole surgical technique were deprived of nutrients for longer periods of time than kidneys obtained for transplant using open surgery, but this does not appear to have any short-term consequences.

10.1002/14651858.CD006124.pub2

cochrane-simplification-train-2349

cochrane-simplification-train-2349

We included six trials involving 497 participants to study efficacy. They showed some benefit (e.g. reduction of cough at day seven) from mucolytic agents, although differences were of little clinical relevance. No conclusion was drawn about the subgroup of infants younger than two years because data were unavailable. Thirty-four studies, including the previous six trials involving 2064 children, were eligible to study safety. Overall safety was good but very few data were available to evaluate safety in infants younger than two years. However, 59 cases of paradoxically increased bronchorrhoea observed in infants were reported to the French pharmacovigilance system. The results have to be interpreted with caution because they are based on a limited number of participants included in studies whose methodological quality is questionable. Acetylcysteine and carbocysteine seem to have a limited efficacy and appear to be safe in children older than two years. These results should take into consideration the fact that acetylcysteine and carbocysteine are prescribed for self limiting diseases (for example, acute cough, bronchitis). Given strong concerns about safety, these drugs should only be used for acute upper and lower RTIs in the context of a RCT with regards to children younger than two years.

Forty-nine trials met the inclusion criteria. Six trials involving 497 participants were included to study efficacy, and compared acetylcysteine or carbocysteine to placebo. Thirty-four trials (including the previous six) were eligible to study safety and involved 2064 paediatric patients. The results of this review suggest actual but limited efficacy of acetylcysteine and carbocysteine (e.g. reduction of cough at day seven) and good overall safety (except for rare mild gastrointestinal side effects) among children older than two years of age. However, the number of participants included was limited and the methodological quality was questionable. These results should also take into consideration the fact that acetylcysteine and carbocysteine are prescribed for self limiting diseases (for example, acute cough, bronchitis). In children younger than two years, and given strong concerns about safety (increased instead of decreased bronchial secretions), these drugs should only be used for acute upper and lower respiratory tract infections in the context of a randomised controlled trial.

10.1002/14651858.CD003124.pub4

cochrane-simplification-train-2350

cochrane-simplification-train-2350

We identified 60 studies, enrolling 3802 recipients. Twenty-nine studies (2262 participants) compared calcium channel blockers (CCB) to placebo/no treatment, 10 studies (445 participants) compared angiotensin converting enzyme inhibitors (ACEi) to placebo/no treatment and seven studies (405 participants) compared CCB to ACEi. CCB compared to placebo/no treatment (plus additional agents in either arm as required) reduced graft loss (RR 0.75, 95% CI 0.57 to 0.99) and improved glomerular filtration rate (GFR), (MD, 4.45 mL/min, 95% CI 2.22 to 6.68). Data on ACEi versus placebo/no treatment were inconclusive for GFR (MD -8.07 mL/min, 95% CI -18.57 to 2.43), and variable for graft loss, precluding meta-analysis. In direct comparison with CCB, ACEi decreased GFR (MD -11.48 mL/min, 95% CI -5.75 to -7.21), proteinuria (MD -0.28 g/24 h, 95% CI -0.47 to -0.10), haemoglobin (MD -12.96 g/L, 95% CI -5.72 to -10.21) and increased hyperkalaemia (RR 3.74, 95% CI 1.89 to 7.43). Graft loss data were inconclusive (RR 7.37, 95% CI 0.39 to 140.35). Other drug comparisons were compared in small numbers of participants and studies. These data suggest that CCB may be preferred as first line agents for hypertensive kidney transplant recipients. ACEi have some detrimental effects in kidney transplant recipients. More high quality studies reporting patient centred outcomes are required.

We found that calcium channel blockers (CCB) reduced the risk of graft loss by about 25% in randomised studies, compared to placebo or no treatment. CCB also improved the function of grafts, as measured by glomerular filtration rate (GFR) with GFR 4.5 mL/min higher on average in patients receiving CCB compared to placebo. There were fewer studies comparing angiotensin converting enzyme inhibitors (ACEi) to placebo and their results were inconclusive. In studies that compared ACEi to CCB, ACEi worsened GFR by about 11.5 mL/min on average. ACEi also lowered haemoglobin and increased the risk of elevated blood potassium compared to CCB. There were not enough studies of other classes of drugs to draw conclusions about their relative effects. On current evidence CCB might therefore be the best agents for kidney transplant patients.

10.1002/14651858.CD003598.pub2

cochrane-simplification-train-2351

cochrane-simplification-train-2351

Searches identified seven publications relating to four studies. We excluded three studies. One post hoc (secondary) analysis of a study published in four reports assessed the efficacy of hydromorphone in neuropathic pain, satisfied our inclusion criteria, and was included in the review. The single included study had an enriched enrolment, randomised withdrawal design with 94 participants who were successfully switched from oral morphine to oral hydromorphone extended release (about 60% of those enrolled). These participants were then randomised to continuing hydromorphone for 12 weeks or tapering down the hydromorphone dose to placebo. The methodological quality of the study was generally good, but we judged the risk of bias for incomplete outcome data as unclear, and for study size as high. Since we identified only one study for inclusion, we were unable to carry out any analyses. The included study did not report any of our prespecified primary outcomes, which relate to the number of participants achieving moderate or substantial levels of pain relief. It did report a slightly larger increase in average pain intensity for placebo in the randomised withdrawal phase than for continuing with hydromorphone. It also reported the number of participants who withdrew due to lack of efficacy in the randomised withdrawal phase, which may be an indicator of efficacy. However, in addition to using an enriched enrolment, randomised withdrawal study design, there was an unusual choice of imputation methods for withdrawals (about 50% of participants); the evidence was of very low quality and inadequate to make a judgement on efficacy. Adverse events occurred in about half of participants with hydromorphone, the most common being constipation and nausea. A similar proportion of participants experienced adverse events with placebo, the most common being opioid withdrawal syndrome (very low quality evidence). Most adverse events were mild or moderate in intensity. One in eight participants withdrew while taking hydromorphone during the conversion and titration phase, despite participants being opioid-tolerant (very low quality evidence). We downgraded the quality of the evidence to very low because there was only one study with few participants, it did not report clinically useful efficacy outcomes, and it was a post hoc analysis. There was insufficient evidence to support or refute the suggestion that hydromorphone has any efficacy in any neuropathic pain condition.

In November 2015, we searched for clinical trials where hydromorphone was used to treat neuropathic pain in adults. We found one small study that did this and met our requirements for the review. The study had a complicated design. Only a minority of participants had neuropathic pain, with only 94 in the comparison with placebo. Important pain outcomes were not reported. The study provided no convincing evidence of any benefit for hydromorphone over placebo. Of those people who started taking hydromorphone, one in eight stopped because of side effects in the first part of the study. The most common side effects were constipation and nausea, which are typically experienced with opioids. We rated the quality of the evidence as very low because of the study design, poor reporting of important outcomes, and small numbers of participants. Very low quality evidence means that we are very uncertain about the results.

10.1002/14651858.CD011604.pub2

cochrane-simplification-train-2352

cochrane-simplification-train-2352

A total of 155 studies met the inclusion criteria; 107 studies provided sufficient data for quantitative synthesis. The results from the caries severity data indicate that the initiation of water fluoridation results in reductions in dmft of 1.81 (95% CI 1.31 to 2.31; 9 studies at high risk of bias, 44,268 participants) and in DMFT of 1.16 (95% CI 0.72 to 1.61; 10 studies at high risk of bias, 78,764 participants). This translates to a 35% reduction in dmft and a 26% reduction in DMFT compared to the median control group mean values. There were also increases in the percentage of caries free children of 15% (95% CI 11% to 19%; 10 studies, 39,966 participants) in deciduous dentition and 14% (95% CI 5% to 23%; 8 studies, 53,538 participants) in permanent dentition. The majority of studies (71%) were conducted prior to 1975 and the widespread introduction of the use of fluoride toothpaste. There is insufficient information to determine whether initiation of a water fluoridation programme results in a change in disparities in caries across socioeconomic status (SES) levels. There is insufficient information to determine the effect of stopping water fluoridation programmes on caries levels. No studies that aimed to determine the effectiveness of water fluoridation for preventing caries in adults met the review's inclusion criteria. With regard to dental fluorosis, we estimated that for a fluoride level of 0.7 ppm the percentage of participants with fluorosis of aesthetic concern was approximately 12% (95% CI 8% to 17%; 40 studies, 59,630 participants). This increases to 40% (95% CI 35% to 44%) when considering fluorosis of any level (detected under highly controlled, clinical conditions; 90 studies, 180,530 participants). Over 97% of the studies were at high risk of bias and there was substantial between-study variation. There is very little contemporary evidence, meeting the review's inclusion criteria, that has evaluated the effectiveness of water fluoridation for the prevention of caries. The available data come predominantly from studies conducted prior to 1975, and indicate that water fluoridation is effective at reducing caries levels in both deciduous and permanent dentition in children. Our confidence in the size of the effect estimates is limited by the observational nature of the study designs, the high risk of bias within the studies and, importantly, the applicability of the evidence to current lifestyles. The decision to implement a water fluoridation programme relies upon an understanding of the population's oral health behaviour (e.g. use of fluoride toothpaste), the availability and uptake of other caries prevention strategies, their diet and consumption of tap water and the movement/migration of the population. There is insufficient evidence to determine whether water fluoridation results in a change in disparities in caries levels across SES. We did not identify any evidence, meeting the review's inclusion criteria, to determine the effectiveness of water fluoridation for preventing caries in adults. There is insufficient information to determine the effect on caries levels of stopping water fluoridation programmes. There is a significant association between dental fluorosis (of aesthetic concern or all levels of dental fluorosis) and fluoride level. The evidence is limited due to high risk of bias within the studies and substantial between-study variation.

We reviewed 20 studies on the effects of fluoridated water on tooth decay and 135 studies on dental fluorosis. The evidence is up to date at 19 February 2015. Nineteen studies assessed the effects of starting a water fluoridation scheme. They compared tooth decay in two communities around the time fluoridation started in one of them. After several years, a second survey was done to see what difference it made. Around 70% of these studies were conducted before 1975. Other, more recent studies comparing fluoridated and non-fluoridated communities have been conducted. We excluded them from our review because they did not carry out initial surveys of tooth decay levels around the time fluoridation started so were unable to evaluate changes in those levels since then. We reviewed one study that compared tooth decay in two fluoridated areas before fluoridation was stopped in one area. Again, after several years, a second survey was done to see what difference it made. Around 73% of dental fluorosis studies were conducted in places with naturally occurring – not added – fluoride in their water. Some had levels of up to 5 parts per million (ppm). Our review found that water fluoridation is effective at reducing levels of tooth decay among children. The introduction of water fluoridation resulted in children having 35% fewer decayed, missing and filled baby teeth and 26% fewer decayed, missing and filled permanent teeth. We also found that fluoridation led to a 15% increase in children with no decay in their baby teeth and a 14% increase in children with no decay in their permanent teeth. These results are based predominantly on old studies and may not be applicable today. Within the ‘before and after’ studies we were looking for, we did not find any on the benefits of fluoridated water for adults. We found insufficient information about the effects of stopping water fluoridation. We found insufficient information to determine whether fluoridation reduces differences in tooth decay levels between children from poorer and more affluent backgrounds. Overall, the results of the studies reviewed suggest that, where the fluoride level in water is 0.7 ppm, there is a chance of around 12% of people having dental fluorosis that may cause concern about how their teeth look. We assessed each study for the quality of the methods used and how thoroughly the results were reported. We had concerns about the methods used, or the reporting of the results, in the vast majority (97%) of the studies. For example, many did not take full account of all the factors that could affect children’s risk of tooth decay or dental fluorosis. There was also substantial variation between the results of the studies, many of which took place before the introduction of fluoride toothpaste. This makes it difficult to be confident of the size of the effects of water fluoridation on tooth decay or the numbers of people likely to have dental fluorosis at different levels of fluoride in the water.

10.1002/14651858.CD010856.pub2

cochrane-simplification-train-2353

cochrane-simplification-train-2353

Nine trials involving a total of 448 participants were included. We judged two trials to be at unclear risk of bias and seven to be at high risk of bias. The majority of items of risk of bias were evaluated to be at unclear or high risk level in more than 50% of the included trials. Each trial except two was addressing a different type of intervention. All evidence was rated as being of very low quality due to problems with risk of bias and imprecision of results, the latter being due to very small sample sizes, low event rates, 95% confidence intervals including the possibility of benefit for both the test and control groups, or combinations of these problems. This means that we are very uncertain about all of the results presented in this review. One trial compared metal-free single crowns (full contour zirconia) to cast gold single crowns in 224 participants and found insufficient evidence of a difference in failure rate after one year, but after five years there was some evidence of a benefit for the gold crowns. There was insufficient evidence of a difference for crown complications at either time of assessment. One trial compared three-unit metal-free FDPs (lithium disilicate) to three-unit metal-ceramic FDPs in 37 participants. There was insufficient evidence of a difference in bridge failure at one and six years, but some evidence of a benefit for the lithium disilicate group in terms of bridge complications at six years. One trial compared zirconia-ceramic FDPs to metal-ceramic FDPs in 34 participants but found insufficient evidence of a difference in bridge failures (i.e. no failures in either treatment group), bridge complications or patients' aesthetic evaluation at any time of assessment up to three years. One trial compared metal-free cantilevered FDPs to metal-ceramic cantilevered FDPs in 21 participants. There was insufficient evidence of a difference for any primary outcome: bridge failures (i.e. no failures in either treatment group), bridge complications, or patients' aesthetic evaluation at any time of assessment up to three years. One trial compared metal-free implant-supported screw retained single crowns (zirconia veneered with feldspathic ceramic) to metal-ceramic implant-supported screw-retained single crowns in 20 participants. There was insufficient evidence of a difference for any primary outcome: crown failures (i.e. no failures in either treatment group), crown complications, or satisfaction/aesthetic evaluation at any time of assessment up to two years. Two trials compared metal-free implant abutments (zirconia) to metal implant abutments both supporting single crowns in 50 participants. There was insufficient evidence of a difference in abutment failure at one year. One trial compared metal-free implant-supported FDPs made of two different types of zirconia ceramic in 18 participants. There was insufficient evidence of a difference in failures at any time of assessment up to 10 years (i.e. no failures in either treatment group). There was some evidence of a benefit for the zirconia-toughened alumina group in terms of complications (chipping). One trial compared metal-free tooth-supported FDPs made with two different veneering techniques (pressed versus layered) in 40 participants. There was insufficient evidence of a difference for failures (i.e. no failures in either treatment group) or complications at any time of assessment up to three years. There is insufficient evidence to support or refute the effectiveness of metal-free materials for fixed prosthodontic treatment over metal-ceramic or other type of standard restorations. The overall quality of existing evidence was very low, therefore great caution should be exercised when generalising the results of the included trials. Until more evidence becomes available clinicians should continue to base decisions on which material to use for fixed prosthodontic treatment on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients. There is urgent need of properly designed RCTs.

This review of existing studies was carried out by Cochrane Oral Health authors and the evidence is current up to 3 May 2017. We searched scientific databases for randomised controlled trials (studies where people are randomly put into one of two or more treatment groups) comparing different types of materials for prosthodontic treatment in people who were followed up for at least one year. Of the nine included trials three were conducted in Germany, one in Sweden, one in Spain, one in Switzerland and the USA, one in Denmark, one in Italy, and one in Switzerland. All the included trials were single-centre conducted at university dental clinics and had a parallel-group study design. All the included trials received support from industry. The review included nine studies with 448 participants in which a total of 224 crowns and 132 bridges on natural teeth, and a total of 74 crowns and 25 bridges on implants were used. Each trial was addressing a different type of intervention. The studies had durations up to 10 years but included very small numbers of participants and were assessed as at unclear or high risk of bias. Based on these studies, there is currently insufficient reliable evidence to support which of these materials are more effective. Two trials were at unclear risk of bias and seven were at high risk of bias. The overall quality of evidence was very low, therefore caution should be exercised when generalising the results of the included trials. Future research should aim to provide more reliable information which can help clinicians to decide on appropriate materials for fixed prosthodontic treatment whilst taking into consideration the individual circumstances and preferences of their patients.

10.1002/14651858.CD009606.pub2

cochrane-simplification-train-2354

cochrane-simplification-train-2354

A total of 17 trials involving 1061 participants (range 13 to 213 participants per trial) were included. Of these, 16 trials compared either deferiprone alone with desferrioxamine alone, or a combined therapy of deferiprone and desferrioxamine with either deferiprone alone or desferrioxamine alone; one compared different schedules of deferiprone. There was little consistency between outcomes and limited information to fully assess the risk of bias of most of the included trials. Four trials reported mortality; each reported the death of one individual receiving deferiprone with or without desferrioxamine. One trial reported five further deaths in patients who withdrew from randomised treatment (deferiprone with or without desferrioxamine) and switched to desferrioxamine alone. Seven trials reported cardiac function or liver fibrosis as measures of end organ damage. Earlier trials measuring the cardiac iron load indirectly by magnetic resonance imaging (MRI) T2* signal had suggested deferiprone may reduce cardiac iron more quickly than desferrioxamine. However, a meta-analysis of two trials suggested that left ventricular ejection fraction was significantly reduced in patients who received desferrioxamine alone compared with combination therapy. One trial, which planned five years of follow up, was stopped early due to the beneficial effects of combined treatment compared with deferiprone alone in terms of serum ferritin levels reduction. The results of this and three other trials suggest an advantage of combined therapy over monotherapy to reduce iron stores as measured by serum ferritin. There is, however, no conclusive or consistent evidence for the improved efficacy of combined deferiprone and desferrioxamine therapy over monotherapy from direct or indirect measures of liver iron. Both deferiprone and desferrioxamine produce a significant reduction in iron stores in transfusion-dependent, iron-overloaded people. There is no evidence from randomised controlled trials to suggest that either has a greater reduction of clinically significant end organ damage. Evidence of adverse events were observed in all treatment groups. Occurrence of any adverse event was significantly more likely with deferiprone than desferrioxamine in one trial, RR 2.24 (95% CI 1.19 to 4.23). Meta-analysis of a further two trials showed a significant increased risk of adverse events associated with combined deferiprone and desferrioxamine compared with desferrioxamine alone, RR 3.04 (95% CI 1.18 to 7.83). The most commonly reported adverse event was joint pain, which occurred significantly more frequently in patients receiving deferiprone than desferrioxamine, RR 2.64 (95% CI 1.21 to 5.77). Other common adverse events included gastrointestinal disturbances as well as neutropenia or leucopenia, or both. In the absence of data from randomised controlled trials, there is no evidence to suggest the need for a change in current treatment recommendations; namely that deferiprone is indicated for treating iron overload in people with thalassaemia major when desferrioxamine is contraindicated or inadequate. Intensified desferrioxamine treatment (by either subcutaneous or intravenous route) or use of other oral iron chelators, or both, remains the established treatment to reverse cardiac dysfunction due to iron overload. Indeed, the US Food and Drug Administration (FDA) recently only gave support for deferiprone to be used as a last resort for treating iron overload in thalassaemia, myelodysplasia and sickle cell disease. However, there is evidence that adverse events are increased in patients treated with deferiprone compared with desferrioxamine and in patients treated with combined deferiprone and desferrioxamine compared with desferrioxamine alone. There is an urgent need for adequately-powered, high-quality trials comparing the overall clinical efficacy and long-term outcome of deferiprone with desferrioxamine.

Seventeen randomised controlled trials compared deferiprone with desferrioxamine. They report little data on death or end organ damage, so we report the effects of therapy using mainly other markers. Removing excess iron was assessed by iron concentration in the blood and liver; heart function; and the amount of iron passed in urine. However, the amount of iron removed with either deferiprone or desferrioxamine was not consistent; one reason being that outcomes were measured differently. This makes it difficult to compare results between trials. Adverse events included joint pain, nausea, stomach upsets and low white blood cell count with deferiprone and pain or skin reactions at the injection site and joint pain with desferrioxamine. In one trial, the risk of an adverse event with deferiprone was twice that of the risk with desferrioxamine. Two further trials showed a three-fold increased risk of an adverse event with combined deferiprone and desferrioxamine therapy compared with desferrioxamine alone. We found no evidence to change current recommendations to treat iron overload in thalassaemia with deferiprone when desferrioxamine cannot be used or is inadequate. Intensified desferrioxamine treatment or use of other oral iron chelators (or both of these) remains the established treatment to reverse heart problems due to iron overload. Indeed, the US Food and Drug Administration (FDA) recently gave support for deferiprone only to be used as a last resort treatment in patients with thalassaemia, myelodysplasia and sickle cell disease. The danger of raised liver enzymes or a very low white blood cell count with deferiprone means that this treatment should not be used unless close monitoring of full blood counts and liver function is possible. Large trials of chelation therapy with standardised measures of iron stores and end organ damage are needed so valuable trial data can be compared and analysed.

10.1002/14651858.CD004839.pub3

cochrane-simplification-train-2355

cochrane-simplification-train-2355

We identified 14 studies that met our inclusion criteria, with a total of 6641 randomised participants, of whom 5638 completed the study. All studies lasted between two and 78 weeks and showed good methodological quality overall. We included 10 comparisons in this review, seven for which the dose of VI and FF was 100/25 mcg (VI/FF 100/25 mcg vs placebo; VI/FF 100/25 mcg vs same dose of FF; VI/FF 100/25 mcg vs same dose of VI; VI/FF 100/25 mcg vs fluticasone propionate (FP) 500 mcg twice-daily; VI/FF 100/25 mcg vs fluticasone propionate/salmeterol (FP/SAL) 250/50 mcg twice-daily; VI/FF 100/25 mcg vs FP/SAL 250/25 mcg twice-daily; FF/VI 100/25 vs FP/SAL500/50) and three for which the dose of VI and FF was 200/25 mcg (VI/FF 200/25 mcg vs placebo; VI/FF 200/25 mcg vs FP 500 mcg; VI/FF 200/25 mcg vs same dose of FF). We found very few opportunities to combine results from the 14 included studies in meta-analyses. We tabulated the data for our pre-specified primary outcomes. In particular, we found insufficient information to assess whether once-daily VI/FF was better or worse than twice-daily FP/SAL in terms of efficacy or safety. Only one of the 14 studies looked at health-related quality of life when comparing VI and FF 100/25 mcg versus placebo and identified a significant advantage of VI/FF 100/25 mcg (mean difference (MD) 0.30, 95% confidence interval (CI) 0.14 to 0.46; 329 participants); we recognised this as moderate-quality evidence. Only two studies compared VI/FF 100/25 mcg versus placebo with respect to exacerbations; both studies reported no exacerbations in either treatment arm. Five studies (VI/FF 100/25 mcg vs placebo) sought information on serious adverse events; all five studies reported no serious adverse events in the VI/FF 100/25 mcg or placebo arms. We found no comparison relevant to our primary outcomes for VI/FF at a higher dose (200/25 mcg) versus placebo. The small number of studies contributing to each comparison precludes the opportunity to draw robust conclusions for clinical practice. These studies were not of sufficient duration to allow conclusions about long-term side effects. Some evidence suggests clear advantages for VI/FF, in combination, compared with placebo, particularly for forced expiratory volume in one second (FEV1) and peak expiratory flow; however, the variety of questions addressed in the included studies did not allow review authors to draw firm conclusions. Information was insufficient for assessment of whether once-daily VI/FF was better or worse than twice-daily FP/SAL in terms of efficacy or safety. It is clear that more research is required to reduce the uncertainties that surround interpretation of these studies. It will be necessary for these findings to be replicated in other work before more robust conclusions are revealed. Only five of the 13 included studies provided data on health-related quality of life, and only six recorded asthma exacerbations. Only one study focused on paediatric patients, so no conclusions can be drawn for the paediatric population. More research is needed, particularly in the primary outcome areas selected for this review, so that we can draw firmer conclusions in the next update of this review.

We included 14 studies in this review, involving a total of 6641 participants. All studies lasted between two and 78 weeks. All people included in these studies had received a diagnosis of asthma. Trials included both men and women, and one study included children and young people. All studies looked at VI and FF versus another medication or placebo. In all studies, the VI/FF combination was taken through a dry powder inhaler. We found that participants who received a combination of FF and VI therapy had improved lung function compared with those given placebo, but evidence was insufficient to permit any other conclusions because researchers attempted to answer too many different questions. Evidence was lacking on whether the combination of VI and FF therapy once-daily is better or worse than a twice-daily alternative. More studies are needed, so that we can gain a better understanding of the evidence overall. Overall, the evidence presented in this review is taken from well-designed studies at low risk of bias in terms of decisions on who received which treatment, blinding and how to report outcomes for participants who did not finish the study. However, because we were not able to combine results for many of our outcomes of interest, or because the outcome was rare, we judged the quality of the evidence overall to be low to moderate.

10.1002/14651858.CD010758.pub2

cochrane-simplification-train-2356

cochrane-simplification-train-2356

We included 96 studies published between 1955 and 2014 in this updated review. Seven studies with 11,356 randomised participants (7047 evaluated) reported the effects of fluoride toothpaste up to 1500 ppm on the primary dentition; one study with 2500 randomised participants (2008 evaluated) reported the effects of 1450 ppm fluoride toothpaste on the primary and permanent dentition; 85 studies with 48,804 randomised participants (40,066 evaluated) reported the effects of toothpaste up to 2400 ppm on the immature permanent dentition; and three studies with 2675 randomised participants (2162 evaluated) reported the effects of up to 1100 ppm fluoride toothpaste on the mature permanent dentition. Follow-up in most studies was 36 months. In the primary dentition of young children, 1500 ppm fluoride toothpaste reduces caries increment when compared with non-fluoride toothpaste (MD -1.86 dfs, 95% confidence interval (CI) -2.51 to -1.21; 998 participants, one study, moderate-certainty evidence); the caries-preventive effects for the head-to-head comparison of 1055 ppm versus 550 ppm fluoride toothpaste are similar (MD -0.05, dmfs, 95% CI -0.38 to 0.28; 1958 participants, two studies, moderate-certainty evidence), but toothbrushing with 1450 ppm fluoride toothpaste slightly reduces decayed, missing, filled teeth (dmft) increment when compared with 440 ppm fluoride toothpaste (MD -0.34, dmft, 95%CI -0.59 to -0.09; 2362 participants, one study, moderate-certainty evidence). The certainty of the remaining evidence for this comparison was judged to be low. We included 81 studies in the network meta-analysis of D(M)FS increment in the permanent dentition of children and adolescents. The network included 21 different comparisons of seven fluoride concentrations. The certainty of the evidence was judged to be low with the following exceptions: there was high- and moderate-certainty evidence that 1000 to 1250 ppm or 1450 to 1500 ppm fluoride toothpaste reduces caries increments when compared with non-fluoride toothpaste (SMD -0.28, 95% CI -0.32 to -0.25, 55 studies; and SMD -0.36, 95% CI -0.43 to -0.29, four studies); there was moderate-certainty evidence that 1450 to 1500 ppm fluoride toothpaste slightly reduces caries increments when compared to 1000 to 1250 ppm (SMD -0.08, 95% CI -0.14 to -0.01, 10 studies); and moderate-certainty evidence that the caries increments are similar for 1700 to 2200 ppm and 2400 to 2800 ppm fluoride toothpaste when compared to 1450 to 1500 ppm (SMD 0.04, 95% CI -0.07 to 0.15, indirect evidence only; SMD -0.05, 95% CI -0.14 to 0.05, two studies). In the adult permanent dentition, 1000 or 1100 ppm fluoride toothpaste reduces DMFS increment when compared with non-fluoride toothpaste in adults of all ages (MD -0.53, 95% CI -1.02 to -0.04; 2162 participants, three studies, moderate-certainty evidence). The evidence for DMFT was low certainty. Only a minority of studies assessed adverse effects of toothpaste. When reported, effects such as soft tissue damage and tooth staining were minimal. This Cochrane Review supports the benefits of using fluoride toothpaste in preventing caries when compared to non-fluoride toothpaste. Evidence for the effects of different fluoride concentrations is more limited, but a dose-response effect was observed for D(M)FS in children and adolescents. For many comparisons of different concentrations the caries-preventive effects and our confidence in these effect estimates are uncertain and could be challenged by further research. The choice of fluoride toothpaste concentration for young children should be balanced against the risk of fluorosis.

Authors fromCochrane Oral Healthcarried out this review and the evidence is current up to 15 August 2018. It includes 96 studies published between 1955 and 2014: seven studies with 11,356 randomised participants reported the effects of fluoride toothpaste up to 1500 ppm on the primary teeth; one study with 2500 randomised participants reported the effects of 1450 ppm toothpaste on the primary and permanent dentition; 85 studies with 48,804 randomised participants reported the effects of toothpaste up to 2400 ppm on the permanent teeth of children up to 18 years of age; and three studies with 2675 randomised participants reported the effects of up to 1100 ppm toothpaste on the permanent teeth of adults. Most studies assessed decay after participants had been using the toothpastes for 36 months. We present below findings for which there is moderate- or high-certainty evidence. In primary teeth of young children, brushing teeth with a toothpaste containing 1500 ppm fluoride reduced the amount of new decay when compared with non-fluoride toothpaste; the amount of new decay was similar with 1055 ppm compared with 550 ppm fluoride toothpaste; and there was a slight reduction in the amount of new decay with 1450 ppm toothpaste compared with 440 ppm fluoride toothpaste. Eighty-one studies assessed the effects of different strengths of fluoride toothpaste compared against each other (seven different strengths in 21 combinations) in permanent teeth of children and adolescents. We found that there was less new decay when toothbrushing with toothpaste containing 1000 to 1250 ppm or 1450 to 1500 ppm fluoride compared with non-fluoride toothpaste, and that toothbrushing with 1450 to 1500 ppm fluoride toothpaste reduced the amount of new decay more than 1000 to 1250 ppm toothpaste. We found that there was a similar amount of new decay when children and adolescents used a toothpaste of 1700 to 2200 ppm or 2400 to 2800 ppm fluoride compared to 1450 to 1500 ppm toothpaste. The evidence for the effects of other strengths of toothpaste was less certain. In permanent teeth of adults of all ages, 1000 or 1100 ppm toothpaste reduced decay compared with non-fluoride toothpaste. Most studies did not measure harmful effects of toothpaste use, but when reported, effects such as soft tissue damage and tooth staining were minimal. There is high-certainty evidence that toothpaste containing 1000 to 1250 ppm fluoride is more effective than non-fluoride toothpaste. There is moderate-certainty evidence for the other findings reported in 'Main results' above. For other toothpaste strengths compared against each other or against non-fluoride toothpaste, there are too few studies with too few participants to have any clarity about the effects. There are benefits of using fluoride toothpaste at certain strengths to prevent tooth decay when compared with non-fluoride toothpaste. The stronger the fluoride concentration, the more decay is prevented. For many of the comparisons of different strengths of toothpaste, the findings are uncertain and could be challenged by further research. The choice of fluoride toothpaste for young children should be balanced against the risk of fluorosis.

10.1002/14651858.CD007868.pub3

cochrane-simplification-train-2357

cochrane-simplification-train-2357

We included six RCTs with 527 participants. Only one RCT was judged to be at low risk of bias. The remaining five RCTs were at unclear or high risk of bias. No trial mentioned the primary outcomes of longest follow-up mortality, Glasgow Outcome Scale score at three months or any adverse events related to mannitol or hypertonic saline. Three trials mentioned the secondary outcomes of intraoperative brain relaxation, hospital stay and ICU stay; quality of life was not reported in any of the trials. Brain relaxation was inadequate in 42 of 197 participants in the hypertonic saline group and in 68 of 190 participants in the mannitol group. The risk ratio for brain bulge or tense brain in the hypertonic saline group was 0.60 (95% confidence interval (CI) 0.44 to 0.83, low-quality evidence). One trial reported ICU and hospital stay. The mean (standard deviation (SD)) duration of ICU stay in the mannitol and hypertonic saline groups was 1.28 (0.5) and 1.25 (0.5) days (P value 0.64), respectively; the mean (SD) duration of hospital stay in the mannitol and hypertonic saline groups was 5.7 (0.7) and 5.7 (0.8) days (P value 1.00), respectively From the limited data available on the use of mannitol and hypertonic saline for brain relaxation during craniotomy, it is suggested that hypertonic saline significantly reduces the risk of tense brain during craniotomy. A single trial suggests that ICU stay and hospital stay are comparable with the use of mannitol or hypertonic saline. However, focus on other related important issues such as long-term mortality, long-term outcome, adverse events and quality of life is needed.

The evidence is current to October 2013. We included studies in children (age > 28 days and < 18 years) and adult patients (age > 18 years) of either gender who received mannitol or hypertonic saline during craniotomy for brain tumour. We reran the search in January 2017 and found five potential studies of interest which have been added to a list of ‘Studies Awaiting Classification' and will be incorporated into the formal review findings during the review update. We found six studies with 527 participants. Three studies reported the level of brain relaxation. Hypertonic saline may provide better brain relaxation than mannitol. The length of intensive care unit stay and hospital stay was reported by one study. No study reported on the effects of mannitol and hypertonic saline on mortality, the condition of the patient three months after the operation or patient quality of life. Based on our results, we would expect that of 100 patients who received hypertonic saline during surgery, around 22 patients would fail to have adequate brain relaxation compared with 36 patients given mannitol. The quality of evidence for brain relaxation with use of hypertonic saline is low. Further research is needed to assess more important issues such as long-term mortality, long-term outcomes, adverse events and quality of life with use of the two fluids.

10.1002/14651858.CD010026.pub2

cochrane-simplification-train-2358

cochrane-simplification-train-2358

We included 25 randomised clinical trials described in 45 reports. The trials included a total of 2690 participants aged between five and 17 years. In 17 trials, participants were also diagnosed with various comorbidities. The social skills interventions were described as: 1) social skills training, 2) cognitive behavioural therapy, 3) multimodal behavioural/psychosocial therapy, 4) child life and attention skills treatment, 5) life skills training, 6) the "challenging horizon programme", 7) verbal self-instruction, 8) meta-cognitive training, 9) behavioural therapy, 10) behavioural and social skills treatment, and 11) psychosocial treatment. The control interventions were no intervention or waiting list. The duration of the interventions ranged from five weeks to two years. We considered the content of the social skills interventions to be comparable and based on a cognitive-behavioural model. Most of the trials compared child social skills training or parent training combined with medication versus medication alone. Some of the experimental interventions also included teacher consultations. More than half of the trials were at high risk of bias for generation of the allocation sequence and allocation concealment. No trial reported on blinding of participants and personnel. Most of the trials did not report on differences between groups in medication for comorbid disorders. We used all eligible trials in the meta-analyses, but downgraded the certainty of the evidence to low or very low. We found no clinically relevant treatment effect of social skills interventions on the primary outcome measures: teacher-rated social skills at end of treatment (standardised mean difference (SMD) 0.11, 95% confidence interval (CI) 0.00 to 0.22; 11 trials, 1271 participants; I2 = 0%; P = 0.05); teacher-rated emotional competencies at end of treatment (SMD −0.02, 95% CI −0.72 to 0.68; two trials, 129 participants; I2 = 74%; P = 0.96); or on teacher-rated general behaviour (SMD −0.06 (negative value better), 95% CI −0.19 to 0.06; eight trials, 1002 participants; I2 = 0%; P = 0.33). The effect on the primary outcome, teacher-rated social skills at end of treatment, corresponds to a MD of 1.22 points on the social skills rating system (SSRS) scale (95% CI 0.09 to 2.36). The minimal clinical relevant difference (10%) on the SSRS is 10.0 points (range 0 to 102 points on SSRS). We found evidence in favour of social skills training on teacher-rated core ADHD symptoms at end of treatment for all eligible trials (SMD −0.26, 95% CI −0.47 to −0.05; 14 trials, 1379 participants; I2= 69%; P = 0.02), but the finding is questionable due to lack of support from sensitivity analyses, high risk of bias, lack of clinical significance, high heterogeneity, and low certainty. The studies did not report any serious or non-serious adverse events. The review suggests that there is little evidence to support or refute social skills training for children and adolescents with ADHD. We may need more trials that are at low risk of bias and a sufficient number of participants to determine the efficacy of social skills training versus no training for ADHD. The evidence base regarding adolescents is especially weak.

We found 25 randomised clinical trials (studies where participants with ADHD were randomly assigned to one of two or more groups) involving a total of 2690 participants. The trials lasted between five weeks and two years. The social skills training generally focused on teaching the children how to 'read' the subtle cues in social interaction, such as learning to wait for their turn, knowing when to shift topics during a conversation, and being able to recognise the emotional expressions of others. Social skills training often consists of role play, exercises and games, as well as homework. Children in the control groups either received no intervention or were placed on a waiting list. We found no significant differences between social skills training versus controls on social skills, emotional competencies, and general behaviour as assessed by teachers. Compared with the children who had no social skills training, teachers rated those who had been in the social skills groups as having fewer ADHD symptoms at the end of treatment.. However, this finding was questionable because our other analyses did not support it. We found no indications of harmful effects. All trials suffered from methodological problems such as overestimation of benefits and underestimation of harms. Many studies were also difficult to compare because they involved different interventions. The results from some trials were not very precise, which means it is difficult to be confident in the results. In seven trials, study authors were board members of pharmaceutical companies, had received funding from such companies, or had performed previous research on the topic. We are unable to conclude whether social skills training is beneficial or not for children with ADHD. We need more randomised clinical trials on social skills training for children and adolescents with ADHD that have a sufficient number of participants and higher methodological quality.The evidence base regarding adolescents is especially weak. We found no adverse treatment effects.

10.1002/14651858.CD008223.pub3

cochrane-simplification-train-2359

cochrane-simplification-train-2359

We included 35 studies of which 31 provided data on 7697 women. For the main comparison between cephalosporins versus penicillins, there were 30 studies of which 27 provided data on 7299 women. There was a lack of good quality data and important outcomes often included only small numbers of women. For the comparison of a single cephalosporin versus a single penicillin (Comparison 1 subgroup 1), we found no significant difference between these classes of antibiotics for our chosen most important seven outcomes namely: maternal sepsis - there were no women with sepsis in the two studies involving 346 women; maternal endometritis (risk ratio (RR) 1.11, 95% confidence interval (CI) 0.81 to 1.52, nine studies, 3130 women, random effects, moderate quality of the evidence); maternal wound infection (RR 0.83, 95% CI 0.38 to 1.81, nine studies, 1497 women, random effects, low quality of the evidence), maternal urinary tract infection (RR 1.48, 95% CI 0.89 to 2.48, seven studies, 1120 women, low quality of the evidence) and maternal composite adverse effects (RR 2.02, 95% CI 0.18 to 21.96, three studies, 1902 women, very low quality of the evidence). None of the included studies looked for infant sepsis nor infant oral thrush. This meant we could only conclude that the current evidence shows no overall difference between the different classes of antibiotics in terms of reducing maternal infections after caesarean sections. However, none of the studies reported on infections diagnosed after the initial postoperative hospital stay. We were unable to assess what impact, if any, the use of different classes of antibiotics might have on bacterial resistance. Based on the best currently available evidence, cephalosporins and penicillins have similar efficacy at caesarean section when considering immediate postoperative infections. We have no data for outcomes on the baby, nor on late infections (up to 30 days) in the mother. Clinicians need to consider bacterial resistance and women's individual circumstances.

When comparing cephalosporins against penicillins, we found 27 studies, involving 7299 women as of September 2014. The quality of the studies was generally unclear and three studies reported drug company funding. Cephalosporins and penicillins had similar effects in reducing infections after caesareans and similar adverse effects. However, none of the studies considered infections after the women left hospital. None of the studies looked at outcomes on the babies. Other evidence show tetracyclines can cause discolouration of teeth in children and are best avoided. Consideration also needs to be given to antibiotics compatible with breastfeeding. We were unable to assess bacterial resistance, and this is crucial when considering which antibiotic might be used. At caesarean sections, cephalosporins and penicillins have similar benefits and side effects for mothers when considering infections immediately following the operation but there is no information on babies. Clinicians need to consider bacterial resistance and women's individual circumstances.

10.1002/14651858.CD008726.pub2

cochrane-simplification-train-2360

cochrane-simplification-train-2360

We included 14 trials (854 participants). Eleven studies reported on gender (men: 472, women: 157). Participant age varied from 18 to 74 years. Most participants had a single, mainly non-infected, wound on one foot, which had been there for less than a year. Only seven studies reported whole study duration (there was no follow-up post-treatment), which was on average six months (range: 1 to 12 months). The studies were conducted in Brazil, Ethiopia, Egypt, Indonesia, Mexico, South Korea, and India. Many 'Risk of bias' assessments were rated as unclear risk due to limited information. Six studies had high risk of bias in at least one domain, including selection and attrition bias. Thirteen studies evaluated different interventions for treating existing ulcers, one of them also evaluated prevention of new ulcers. One study aimed to prevent skin changes, such as cracking and fissures. Investigated interventions included: laser therapy, light-emitting diode (LED), zinc tape, intralesional pentoxifylline, pulsed magnetic fields, wax therapy, ketanserin, human amniotic membrane gel, phenytoin, plaster shoes, and footwear. We are uncertain about the following key results, as the certainty of evidence is very low. All time points were measured from baseline. Three studies compared zinc tape versus other interventions and reported results in favour of zinc tape. One study compared zinc tape versus magnesium sulphate: at one month the number of healed ulcers and reduction in mean ulcer area was higher with zinc tape (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.43 to 9.21, and mean difference (MD) -14.30 mm², 95% CI -26.51 to -2.09, respectively, 28 participants). Another study compared zinc tape and povidone iodine and found that even though there was a greater reduction in ulcer area after six weeks of treatment with zinc tape, there was no clear difference due to the wide 95% CI (MD 128.00 mm², 95% CI -110.01 to 366.01; 38 participants). The third study (90 participants) compared adhesive zinc tape with gauze soaked in Eusol, and found the healing time for deep ulcers was less compared to zinc tape: 17 days (95% CI 12 to 20) versus 30 days (95% CI 21 to 63). Adverse events were only collected in the study comparing zinc tape with gauze soaked in Eusol: there were no signs of skin sensitisation in either group at two months. Two studies compared topical phenytoin versus saline dressing and reported results in favour of phenytoin. One study reported a greater mean percentage reduction of ulcer area after four weeks with phenytoin 2% (MD 39.30%, 95% CI 25.82 to 52.78; 23 participants), and the other study reported a greater mean percentage reduction of ulcer volume (16.60%) after four weeks with phenytoin (95% CI 8.46 to 24.74; 100 participants). No adverse events were observed with either treatment during the four-month treatment period (2 studies, 123 participants). Prevention of ulcers was not evaluated in these nor the zinc studies, as the interventions were not for preventative use. Two studies compared protective footwear (with or without self-care) with either 1) polyvinyl chloride (PVC) boots, or 2) pulsed magnetic fields plus self-care and protective footwear. In the study comparing canvas shoes versus PVC boots, none of the 72 participants with scars at the start of the study developed new ulcers over one-year follow-up. Healing of ulcers was assessed in 38 participants from this study, but we are unclear if there is a difference between groups. In the study comparing pulsed magnetic fields (in addition to self-care and protective footwear) to only self-care and footwear in 33 participants, we are uncertain if the mean volume of ulcers at four to five weeks' follow-up was different between groups; this study did not evaluate the prevention of ulcers. Information for adverse events was only reported in the study comparing canvas shoes with PVC boots; the authors stated that the PVC boots could become hot in strong sunlight and possibly burn the feet. Based on the available evidence, we could not draw firm conclusions about the effects of the included interventions. The main evidence limitations were high or unclear risk of bias, including selection, performance, detection, and attrition bias; imprecision due to few participants in the studies; and indirectness from poor outcome measurement and inapplicable interventions. Future research should clearly report important outcomes, such as adverse events, and assess widely available interventions, which should include treatments aimed at prevention. These trials should ensure allocation concealment, blinding, and an adequate sample size.

We included 14 trials (854 participants with leprosy). Participants mostly had only one wound on one foot. Wounds were mainly simple (not infected) and varied in size and depth, and were less than one year old; some wounds were more complicated. Participants ranged from 18 to 74 years old. In the 11 studies which reported gender, more men were included. Studies were conducted in Brazil, Ethiopia, Egypt, Indonesia, Mexico, South Korea, and India, in mainly outpatient clinics. Most studies did not report funding sources. Treatments were mostly compared to dry dressings or dressings soaked in differing solutions. Other comparisons included special plaster, canvas shoes, and foot soak. Treatments evaluated included: laser therapy, light-emitting diode (LED), zinc tape or paste, pentoxifylline injections, exposure to pulsed magnetic fields, wax therapy, ketanserin gel, amniotic membrane gel, phenytoin powder, plaster shoes, and footwear. Outcomes were measured from the beginning of treatment. The following key results are based on very low-certainty evidence, so we are not sure of these results. Three studies compared zinc tape with other interventions: magnesium sulphate glycerin, povidone iodine, or gauze soaked in Eusol. After one month of treatment, the number of healed ulcers was higher and the ulcer area was lower in the zinc tape group compared with magnesium sulphate glycerin. There was no clear difference in the reduction of ulcer area at six weeks when comparing zinc tape to povidone iodine. The healing time for deep ulcers in the zinc tape group was 17 days compared to 30 days with gauze soaked in Eusol. This study also reported no signs of skin sensitisation in either group at two months; the other two studies provided no data on adverse events. Two studies compared topical phenytoin to salt water dressing. One study showed a greater reduction in ulcer area with phenytoin. The other study found a greater reduction in ulcer volume in favour of phenytoin. Both studies measured this outcome after four weeks of treatment. No adverse events were observed in either study. The five studies just described did not assess prevention of ulcers, as the therapies were for treatment rather than prevention. Two studies compared protective footwear (with or without self-care) with either polyvinyl chloride (PVC - a form of plastic) boots, or pulsed magnetic fields plus self-care and protective footwear. In the study comparing canvas shoes versus PVC boots, none of the participants who had scars at the start developed new ulcers over one year. There was no clear difference between the groups in the number of people whose ulcers had healed. In the study assessing pulsed magnetic fields, prevention of new ulcers was not measured; however, there was no clear difference between groups in volume of ulcers four to five weeks after the start of treatment. Only one study reported information about adverse events: the PVC boots could become very hot in strong sunlight, with the possibility of burning. We judged the evidence as very low certainty, meaning the results are ambiguous. There were concerns regarding how participants were allocated to treatments, whether participants and study investigators knew which treatment had been received, and the number of participants who dropped out of the studies.

10.1002/14651858.CD012235.pub2

cochrane-simplification-train-2361

cochrane-simplification-train-2361

No completed studies met the inclusion criteria for the review. Two ongoing trials fulfilled the selection criteria, however neither are complete. 'Early-stage squamous cell carcinoma of the oropharynx: radiotherapy versus trans-oral robotic surgery (ORATOR)' is a phase II randomised controlled trial comparing primary radiation therapy with primary transoral robotic surgery for small-volume primary (T1-2, N0-2) OPSCC. It is currently in progress with an estimated completion date of June 2021. 'European Organisation for Research and Treatment of Cancer 1420 (EORTC 1420-HNCG-ROG)' is a phase III, randomised study assessing the "best of" radiotherapy compared to transoral robotic surgery/transoral laser microsurgery in patients with T1-T2, N0 squamous cell carcinoma of the oropharynx and base of tongue. It was due to start accrual mid-2016. The role of endoscopic head and neck surgery in the management of OPSCC is clearly expanding as evidenced by its more overt incorporation into the current National Comprehensive Cancer Network guidelines. Data are mounting regarding its outcomes both in terms of survival and lower morbidity. As confidence increases, it is being used in the management of more advanced OPSCC. Based on this review, there is currently no high-quality evidence from randomised controlled trials regarding clinical outcomes for patients with oropharyngeal cancer receiving endoscopic head and neck surgery compared with primary chemoradiotherapy.

We found no completed studies that compared keyhole surgery and radiotherapy alone or combined with chemotherapy. Two ongoing trials did fulfil our selection criteria, however neither are yet complete. One has an estimated completion date of June 2021 and the other planned to start recruiting patients mid-2016. There are not yet any completed studies to include in the review so there are no results. The role of keyhole surgery in the management of throat cancer is expanding as is demonstrated by its incorporation into the current national guidelines in the USA. Evidence is mounting regarding its outcomes both in terms of survival and fewer side effects. Based on this review, there is currently no high-quality evidence from randomised controlled trials that compare keyhole surgery with radiotherapy and chemotherapy for patients with throat cancer.

10.1002/14651858.CD010963.pub2

cochrane-simplification-train-2362

cochrane-simplification-train-2362

We included 26 trials (2051 participants). All studies used listening to pre-recorded music. The results suggested that music listening may have a beneficial effect on preoperative anxiety. Specifically, music listening resulted, on average, in an anxiety reduction that was 5.72 units greater (95% CI -7.27 to -4.17, P < 0.00001) than that in the standard care group as measured by the Stait-Trait Anxiety Inventory (STAI-S), and -0.60 standardized units (95% CI -0.90 to -0.31, P < 0.0001) on other anxiety scales. The results also suggested a small effect on heart rate and diastolic blood pressure, but no support was found for reductions in systolic blood pressure, respiratory rate, and skin temperature. Most trials were assessed to be at high risk of bias because of lack of blinding. Blinding of outcome assessors is often impossible in music therapy and music medicine studies that use subjective outcomes, unless in studies in which the music intervention is compared to another treatment intervention. Because of the high risk of bias, these results need to be interpreted with caution. None of the studies included wound healing, infection rate, time to discharge, or patient satisfaction as outcome variables. One large study found that music listening was more effective than the sedative midazolam in reducing preoperative anxiety and equally effective in reducing physiological responses. No adverse effects were identified. This systematic review indicates that music listening may have a beneficial effect on preoperative anxiety. These findings are consistent with the findings of three other Cochrane systematic reviews on the use of music interventions for anxiety reduction in medical patients. Therefore, we conclude that music interventions may provide a viable alternative to sedatives and anti-anxiety drugs for reducing preoperative anxiety.

The review included 26 trials with a total of 2051 participants. The findings suggested that music listening may have a beneficial effect on preoperative anxiety. Most trials presented some methodological weakness. Therefore, these results need to be interpreted with caution. However, these findings are consistent with the findings of three other Cochrane systematic reviews on the use of music interventions for anxiety reduction in medical patients. Therefore, we conclude that music interventions may provide a viable alternative to sedatives and anti-anxiety drugs for reducing preoperative anxiety.

10.1002/14651858.CD006908.pub2

cochrane-simplification-train-2363

cochrane-simplification-train-2363

We included eight studies with 513 participants, providing a total of 47 comparisons of outcome between intervention and control conditions. Nineteen comparisons were statistically significant, all favouring the intervention group. We conducted nine meta-analyses using data from four studies in total (each meta-analysis included data from two studies). Four meta-analyses showed statistically significant findings favouring the intervention group for the following outcomes: parent responsiveness to the child post-intervention (SMD -0.91, 95% CI -1.52 to -0.30, P = 0.04); infant responsiveness to mother at follow-up (SMD -0.65, 95% CI -1.25 to -0.06, P = 0.03); and an overall measure of parent-child interactions post-intervention (SMD -0.71, 95% CI -1.31 to -0.11, P = 0.02), and at follow-up (SMD -0.90, 95% CI -1.51 to -0.30, P = 0.004). The results of the remaining five meta-analyses were inconclusive. Variation in the measures used, the included populations and interventions, and the risk of bias within the included studies limit the conclusions that can be reached. The findings provide some evidence to suggest that parenting programmes may be effective in improving a number of aspects of parent-child interaction both in the short- and long-term, but further research is now needed.

The findings are based on eight studies measuring a variety of outcomes, using a range of standardised measures. It was possible to combine results (meta-analysis) for nine comparisons. Results from four of these meta-analyses suggest that parenting programmes may be effective in improving parent responsiveness to the child, and parent-child interaction, both post-intervention and at follow-up. Infant responsiveness to the mother also showed improvement at follow-up. The results of the other five meta-analyses we carried out were inconclusive. Further rigorous research is needed that provides both short- and long-term follow-up of the children of teenage parents, and that assesses the benefits of parenting programmes for young fathers as well as young mothers.

10.1002/14651858.CD002964.pub2

cochrane-simplification-train-2364

cochrane-simplification-train-2364

We included in this updated review one new study (70 participants), resulting in a total of three RCTs (140 participants who drank 3 to 40 AU/d). All three studies were of moderate to good quality. All studies evaluated the effects of intensive alcohol cessation interventions, including pharmacological strategies for alcohol withdrawal symptoms, patient education, and relapse prophylaxis. We identified one ongoing study. Overall, 53 of the 122 participants from three studies who underwent surgery developed any type of postoperative complication that required treatment. Of 61 participants in the intervention groups, 20 had complications, compared with 33 of 61 participants in the control groups (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.40 to 0.96). Results show differences between the three clinical studies regarding outcome measurement and intensity of the interventions. However, all alcohol cessation programmes were intensive and included pharmacological therapy. The overall quality of evidence for this outcome is moderate. In-hospital and 30-day postoperative mortality rates were low in the three studies. Researchers reported one death among 61 participants in the intervention groups, and three deaths among 61 participants in the control groups (RR 0.47, 95% CI 0.07 to 2.96). The quality of evidence for this outcome is low. Investigators describe more successful quitters at the end of the intervention programme than among controls. Forty-one out of 70 participants in the intervention groups successfully quit drinking compared with only five out of 70 participants in the control groups (RR 8.22, 95% CI 1.67 to 40.44). The quality of evidence for this outcome is moderate. All three studies reported postoperative alcohol consumption (grams of alcohol/week) at the end of the programme as median and range values; therefore it was not possible to estimate the mean and the standard deviation (SD). We performed no meta-analysis. All three studies reported length of stay, and none of these studies described a significant difference in length of stay. Data were insufficient for review authors to perform a meta-analysis. No studies reported on the prevalence of participants without risky drinking in the longer term. This systematic review assessed the efficacy of perioperative alcohol cessation interventions for postoperative complications and alcohol consumption. All three studies showed a significant reduction in the number of participants who quit drinking alcohol during the intervention period. Intensive alcohol cessation interventions offered for four to eight weeks to participants undergoing all types of surgical procedures to achieve complete alcohol cessation before surgery probably reduced the number of postoperative complications. Data were insufficient for review authors to assess their effects on postoperative mortality. No studies reported an effect on length of stay, and no studies addressed the prevalence of risky drinking in the longer term. Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these study results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could have been more motivated and/or more interested in participating in clinical research or otherwise different, and effects may have been overestimated for both intervention and control groups in these studies. Trial results indicate that these studies are difficult to perform, that strong research competencies are necessary for future studies, and that further evaluation of perioperative alcohol cessation interventions in high-quality randomized controlled trials is needed. Once published and assessed, the one 'ongoing' study identified may alter the conclusions of this review.

We included three randomized controlled trials with a total of 140 participants. All three studies included participants with risky alcohol intake (3 to 40 AU daily) who were in need of surgery. These studies investigated intensive alcohol interventions aimed at complete alcohol cessation at the time of surgery compared with no intervention. Interventions included educational strategies for alcohol withdrawal and relapse prevention. Programmes were started three months before surgery, four weeks before surgery, and from the time of admission to surgery, and continued for six weeks after surgery, respectively. The quality of the evidence is of moderate to low quality. In all three studies, intensive intervention programmes clearly increased the number of participants who quit drinking alcohol. The occurrence of postoperative complications appeared to be reduced as well. Of 61 participants in the intervention groups, 20 had complications requiring treatment, compared with 33 of 61 participants in the control groups (moderate-quality evidence). Of 70 participants in the intervention groups, 41 successfully quit drinking, compared to five of 70 participants in the control groups (moderate-quality evidence). Data were insufficient to show the effect of quitting drinking on the number of deaths (low-quality evidence), and results show no effect on length of hospital stay. None of the included studies reported on the number of participants who continued to avoid risky drinking in the longer term (at three-, six-, nine-, and 12-month follow-up). Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could be more motivated and/or more interested in participating in clinical research or otherwise different, and effects may therefore have been overestimated for both intervention and control groups in these studies. More research is needed and new strategies are required to improve outcomes after surgery among risky drinkers.

10.1002/14651858.CD008343.pub3

cochrane-simplification-train-2365

cochrane-simplification-train-2365

Five cluster-RCTs of 111 schools met the review eligibility criteria. Investigators measured outcomes in participating staff and often in children or parents, most often at between 1 and 12 months. All interventions were educational programmes but duration, content and delivery varied; some involved elements of training for pupils or primary care providers. We noted risk of selection, performance, detection and attrition biases, although to a differing extent across studies and outcomes. Quanitative and qualitative analyses were limited. Only one study reported visits to the ED or hospital and provided data that were too skewed for analysis. No studies reported any deaths or adverse events. Studies did not report asthma control consistently, but results showed no difference between groups on the paediatric asthma quality of life questionnaire (mean difference (MD) 0.14, 95% confidence interval (CI) -0.03 to 0.31; 1005 participants; we downgraded the quality of evidence to low for risk of bias and indirectness). Data for symptom days, night-time awakenings, restricted activities of daily living and school absences were skewed or could not be analysed; some mean scores were better in the trained group, but most differences between groups were small and did not persist to 24 months. Schools that received asthma education were more adherent to asthma policies, and staff were better prepared; more schools that had received staff asthma training had written asthma policies compared with control schools, more intervention schools showed improvement in measures taken to prevent or manage exercise-induced asthma attacks and more staff at intervention schools reported that they felt able to administer salbutamol via a spacer. However, the quality of the evidence was low; results show imbalances at baseline, and confidence in the evidence was limited by risk of bias and imprecision. Staff knowledge was higher in groups that had received asthma education, although results were inconsistent and difficult to interpret owing to differences between scales (low quality). Available information about the interventions was insufficient for review authors to conduct a meaningful qualitative synthesis of the content that led to a successful intervention, or of the resources required to replicate results accurately. Asthma education for school staff increases asthma knowledge and preparedness, but studies vary and all available evidence is of low quality. Studies have not yet captured whether this improvement in knowledge has led to appreciable benefits over the short term or the longer term for the safety and health of children with asthma in school. Randomised evidence does not contribute to our knowledge of content or attributes of interventions that lead to the best outcomes, or of resources required for successful implementation. Complete reporting of the content and resources of educational interventions is essential for assessment of their effectiveness and feasibility for implementation. This applies to both randomised and non-randomised studies, although the latter may be better placed to observe important clinical outcomes such as exacerbations and mortality in the longer term.

We found five studies including more than 100 schools that compared an asthma education programme for school staff against a control. Researchers measured outcomes for teachers and staff, and often for children or parents as well, most often at between 1 and 12 months. We conducted the most recent search for studies on 29 November 2016. We could not tell whether educating school staff reduced the number of children who needed to visit the emergency department (ED) or hospital, and no studies reported any deaths. Study authors measured asthma control in different ways but found little benefit, especially more than a year after the intervention was provided. Schools that received asthma education stuck to asthma policies better and staff were better prepared; more schools that had received staff asthma training had written asthma policies compared with control schools, more intervention schools showed improvement in measures taken to prevent or manage exercise-induced asthma attacks and more staff at intervention schools felt that they were able to administer salbutamol using a spacer. We wanted to assess what the education sessions should cover and how they could best be delivered, but we did not find enough information to do this. To sum up, asthma education for school staff increases asthma knowledge and preparedness in the schools, but we do not know much about actual benefits of this education for children with asthma. The small number of studies and the variation between them mean that we cannot be sure of the overall effect of educating school staff about asthma. The ways researchers allocated schools, teachers or children to groups may have caused some bias. Also, the fact that teachers knew whether they were in the active or control group may have affected how they behaved and answered questionnaires, and this may have led to overestimation of benefits. Lots of people who were included in the studies did not return questionnaires at the end of the study, which means that we do not have a full picture of the results of asthma education interventions.

10.1002/14651858.CD012255.pub2

cochrane-simplification-train-2366

cochrane-simplification-train-2366

We identified 15 Cochrane reviews (255 included trials) and three non-Cochrane reviews (55 included trials) for inclusion within this overview. For all interventions, with available data, results are presented as comparisons of: 1. Intervention versus placebo or standard care; 2. Different forms of the same intervention (e.g. one opioid versus another opioid); 3. One type of intervention versus a different type of intervention (e.g. TENS versus opioid). Not all reviews included results for all comparisons. Most reviews compared the intervention with placebo or standard care, but with the exception of opioids and epidural analgesia, there were few direct comparisons between different forms of the same intervention, and even fewer comparisons between different interventions. Based on these three comparisons, we have categorised interventions into: " What works" ,“What may work”, and “Insufficient evidence to make a judgement”. WHAT WORKS Evidence suggests that epidural, combined spinal epidural (CSE) and inhaled analgesia effectively manage pain in labour, but may give rise to adverse effects. Epidural, and inhaled analgesia effectively relieve pain when compared with placebo or a different type of intervention (epidural versus opioids). Combined-spinal epidurals relieve pain more quickly than traditional or low dose epidurals. Women receiving inhaled analgesia were more likely to experience vomiting, nausea and dizziness. When compared with placebo or opioids, women receiving epidural analgesia had more instrumental vaginal births and caesarean sections for fetal distress, although there was no difference in the rates of caesarean section overall. Women receiving epidural analgesia were more likely to experience hypotension, motor blockade, fever or urinary retention. Less urinary retention was observed in women receiving CSE than in women receiving traditional epidurals. More women receiving CSE than low-dose epidural experienced pruritus. WHAT MAY WORK There is some evidence to suggest that immersion in water, relaxation, acupuncture, massage and local anaesthetic nerve blocks or non-opioid drugs may improve management of labour pain, with few adverse effects.  Evidence was mainly limited to single trials. These interventions relieved pain and improved satisfaction with pain relief (immersion, relaxation, acupuncture, local anaesthetic nerve blocks, non-opioids) and childbirth experience (immersion, relaxation, non-opioids) when compared with placebo or standard care. Relaxation was associated with fewer assisted vaginal births and acupuncture was associated with fewer assisted vaginal births and caesarean sections. INSUFFICIENT EVIDENCE There is insufficient evidence to make judgements on whether or not hypnosis, biofeedback, sterile water injection, aromatherapy, TENS, or parenteral opioids are more effective than placebo or other interventions for pain management in labour. In comparison with other opioids more women receiving pethidine experienced adverse effects including drowsiness and nausea. Most methods of non-pharmacological pain management are non-invasive and appear to be safe for mother and baby, however, their efficacy is unclear, due to limited high quality evidence. In many reviews, only one or two trials provided outcome data for analysis and the overall methodological quality of the trials was low. High quality trials are needed. There is more evidence to support the efficacy of pharmacological methods, but these have more adverse effects. Thus, epidural analgesia provides effective pain relief but at the cost of increased instrumental vaginal birth. It remains important to tailor methods used to each woman’s wishes, needs and circumstances, such as anticipated duration of labour, the infant's condition, and any augmentation or induction of labour. A major challenge in compiling this overview, and the individual systematic reviews on which it is based, has been the variation in use of different process and outcome measures in different trials, particularly assessment of pain and its relief, and effects on the neonate after birth. This made it difficult to pool results from otherwise similar studies, and to derive conclusions from the totality of evidence. Other important outcomes have simply not been assessed in trials; thus, despite concerns for 30 years or more about the effects of maternal opioid administration during labour on subsequent neonatal behaviour and its influence on breastfeeding, only two out of 57 trials of opioids reported breastfeeding as an outcome. We therefore strongly recommend that the outcome measures, agreed through wide consultation for this project, are used in all future trials of methods of pain management.

Most of the evidence on non-drug interventions was based on just one or two studies and so the findings are not definitive.  However, we found that immersion in water, relaxation, acupuncture and massage all gave pain relief and better satisfaction with pain relief. Immersion and relaxation also gave better satisfaction with childbirth. Both relaxation and acupuncture decreased the use of forceps and ventouse, with acupuncture also decreasing the number of caesarean sections. There was insufficient evidence to make a judgement on whether or not hypnosis, biofeedback, sterile water injection, aromatherapy, and TENS are effective for pain relief in labour. Overall, there were more studies of drug interventions. Inhaled nitrous oxide and oxygen (Entonox®) relieved pain, but some women felt drowsy, nauseous or were sick.  Non-opioid drugs (e.g. sedatives) relieved pain and some gave greater satisfaction with pain relief than placebo or no treatment, but satisfaction with pain relief was less than with opioids. Epidurals relieved pain, but increased the numbers of births needing forceps or ventouse, and the risk of low blood pressure, motor blocks (hindering leg movement), fever and urine retention. Combined spinal-epidurals gave faster pain relief but more women had itching than with epidurals alone, although urinary retention was less likely to be a problem. Local anaesthetic nerve blocks gave satisfaction but caused side effects of giddiness, sweating, tingling, and more babies had low heart rates. Parenteral opioids (injections of pethidine and related drugs) are less effective than epidural but there was insufficient evidence to make a judgement on whether or not they are more effective than other interventions for pain relief in labour. Overall, women should feel free to choose whatever pain management they feel would help them most during labour. Women who choose non-drug pain management should feel free, if needed, to move onto a drug intervention. During pregnancy, women should be told about the benefits and potential adverse effects on themselves and their babies of the different methods of pain control. Individual studies showed considerable variation in how outcomes such as pain intensity were measured and some important outcomes were rarely or never included (for example, sense of control in labour, breastfeeding, mother and baby interaction, costs and infant outcomes). Further research is needed on the non-drug interventions for pain management in labour.

10.1002/14651858.CD009234.pub2

cochrane-simplification-train-2367

cochrane-simplification-train-2367

We included 10 pharmacological (modafinil, intravenous immunoglobulin (IVIg), pyridostigmine, lamotrigine, amantadine, prednisone) and three non-pharmacological (muscle strengthening, rehabilitation in a warm climate (that is temperature ± 25°C, dry and sunny) and a cold climate (that is temperature ± 0°C, rainy or snowy), static magnetic fields) studies with a total of 675 participants with PPS in this review. None of the included studies were completely free from any risk of bias, the most prevalent risk of bias being lack of blinding. There was moderate- and low-quality evidence that IVIg has no beneficial effect on activity limitations in the short term and long term, respectively, and inconsistency in the evidence for effectiveness on muscle strength. IVIg caused minor adverse events in a substantial proportion of the participants. Results of one trial provided very low-quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations without generating adverse events. Data from two single trials suggested that muscle strengthening of thumb muscles (very low-quality evidence) and static magnetic fields (moderate-quality evidence) are safe and beneficial for improving muscle strength and pain, respectively, with unknown effects on activity limitations. Finally, there was evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS. Due to insufficient good-quality data and lack of randomised studies, it was impossible to draw definite conclusions about the effectiveness of interventions for PPS. Results indicated that IVIg, lamotrigine, muscle strengthening exercises and static magnetic fields may be beneficial but need further investigation to clarify whether any real and meaningful effect exists.

We searched scientific databases to find all studies on treatments for PPS up to July 2014. We found 13 studies involving a total of 675 participants that were of sufficient quality to include in this review. Ten studies evaluated the effects of drugs (modafinil, intravenous immunoglobulin (IVIg), pyridostigmine, lamotrigine, amantadine, prednisone), and three studies evaluated other treatments (muscle strengthening, rehabilitation in a warm climate (that is temperature ± 25°C, dry and sunny) and a cold climate (that is temperature ± 0°C, rainy or snowy), static magnetic fields). IVIg is a treatment in which antibodies that have been purified from donated blood are given as an infusion into a vein over a period of time. There was moderate- and low-quality evidence that IVIg has no beneficial effect on activity limitations in the short term and long term, respectively. Evidence for effectiveness on muscle strength was inconsistent, as results differed across studies. IVIg caused minor side effects in a substantial proportion of the participants. Lamotrigine is a drug used to help control certain kinds of epilepsy and to treat bipolar psychiatric disorder. Results of one trial provided very low-quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations, and in this study it was well-tolerated. We based these conclusions on results of only one small trial with important limitations in study design. There was very low-quality evidence that muscle strengthening of thumb muscles is safe and beneficial for improving muscle strength. Again, we based these conclusions on results of only one small trial with important limitations in study design, and they are applicable only to thumb muscles. Static magnetic fields is a therapy in which electrical currents are applied to the skin with the intention of reducing pain. There was moderate-quality evidence that static magnetic fields are safe and beneficial for reducing pain directly after treatment, although functional effects on activity limitations and long-term effects are unknown. Finally, there was evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS.

10.1002/14651858.CD007818.pub3

cochrane-simplification-train-2368

cochrane-simplification-train-2368

In this update, we identified one new trial. Therefore, this version includes three trials (108 participants). Two trials compared carvedilol against placebo and another assessed rosuvastatin versus placebo. All trials had a high risk of bias. Meta-analysis of two trials showed a lower proportion of all-cause mortality in the carvedilol groups compared with the placebo groups (RR 0.69; 95% CI 0.12 to 3.88, I² = 0%; 69 participants; very low-quality evidence). Neither of the trials reported on cardiovascular mortality, time-to-heart decompensation, or disease-free periods. One trial (30 participants) found no difference in hospital readmissions (RR 1.00; 95% CI 0.31 to 3.28; very low-quality of evidence) or reported adverse events (RR 0.92; 95% CI 0.67 to 1.27; very low-quality of evidence) between the carvedilol and placebo groups. There was very low-quality evidence from two trials of inconclusive effects on quality of life (QoL) between the carvedilol and placebo groups. One trial (30 participants) assessed QoL with the Minnesota Living With Heart Failure Questionnaire (21 items; item scores range from 0 to 5; a lower MLHFQ score is better). The MD was -14.74; 95% CI -24.75 to -4.73. The other trial (39 participants) measured QoL with the Medical Outcomes Study 36-item short-form health survey (SF-36; item scores range from 0 to 100; higher SF-36 score is better). Data were not provided. One trial (39 participants) assessed the effect of rosuvastatin versus placebo. The trial did not report on any primary outcomes or adverse events. There was very low-quality evidence of uncertain effects on QoL (no data were provided). This first update of our review found very low-quality evidence for the effects of either carvedilol or rosuvastatin, compared with placebo, for treating heart failure in people with Chagas disease. The three included trials were underpowered and had a high risk of bias. There were no conclusive data to support or reject the use of either carvedilol or rosuvastatin for treating Chagas cardiomyopathy. Unless randomised clinical trials provide evidence of a treatment effect, and the trade-off between potential benefits and harms is established, policy-makers, clinicians, and academics should be cautious when recommending or administering either carvedilol or rosuvastatin to treat heart failure in people with Chagas disease. The efficacy and safety of other pharmacological interventions for treating heart failure in people with Chagas disease remains unknown.

We identified one new trial, so there are now three studies involving 108 participants. All studies were conducted in Brazil during 2004, 2007, and 2012. Two trials evaluated the effects of carvedilol versus placebo; one trial assessed rosuvastatin versus placebo. The results were inconclusive that carvedilol reduced all-cause mortality or improved quality of life more than placebo. The safety profile of carvedilol for Chagas cardiomyopathy remains unclear. One study assessed the effect of rosuvastatin versus placebo, but did not show an effect size. Therefore, the results from available clinical trials neither support nor reject the use of carvedilol or rosuvastatin in treating this clinical entity. Further investigation is warranted to investigate the exact applicability of conventional heart failure treatment agents in Chagas cardiomyopathy. Our confidence in the results of this review is very low because the included trials had a high risk of bias and were small. which generated imprecise results. 15 February 2016.

10.1002/14651858.CD009077.pub3

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cochrane-simplification-train-2369

Only one study from developing countries met the inclusion criteria and was included in the review. The study, a cluster randomised trial (10 clusters, n=849) compared VCT uptake between an optional location (including home-based) and a local clinic location in a population-based HIV survey. The study showed a higher uptake of VCT among participants in the optional-location group. Uptake was significantly greater in the optional-location group in those who were pre-test counselled only (RR=4.6; 95% CI 3.58 to 5.91); pretest counselled and tested (RR=4.6; 95% CI 3.51 to 5.92); and post-test counselled and received the test result (RR=4.8; 95% CI 3.62 to 6.21). This study, however, had significant methodological problems limiting further analysis and interpretation. Although home-based HIV VCT has the potential to enhance VCT uptake in developing countries, insufficient data exist to recommend large-scale implementation of home-based HIV testing. Further studies are needed to determine if home-based VCT is better than facility-based VCT in improving VCT uptake.

This review attempted to evaluate this assumption. We found only one published study from developing countries and none from developed countries. The only study included in the review showed an increase in VCT uptake after home-based VCT intervention. Because of the limited evidence to date, however, further research is needed to evaluate if home-based VCT is better than facility-based VCT or other testing methods.

10.1002/14651858.CD006493.pub4

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cochrane-simplification-train-2370

12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias. Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes. Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue. Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.

We found 12 studies, eight weeks in duration, that randomly assigned 7439 adult people with uncomplicated mild-to-moderate hypertension to aliskiren at doses ranging from 75 mg to 600 mg or placebo. All studies were funded by the manufacturer Novartis. Detailed information regarding adverse events, obtained from nine clinical study reports submitted to regulators, are included in this update. We concluded that aliskiren is better than placebo at lowering blood pressure and that the magnitude of this effect could be similar to other classes of drugs when 300 mg, which is the maximum recommended dose, is used. Aliskiren 300 mg reduced blood pressure by eight points in the upper number (called systolic blood pressure) and five points in the lower number (called diastolic blood pressure). Aliskiren had no effect on blood pressure changeability. Due to very limited information regarding change in heart rate and pulse pressure (difference between upper and lower number) it was not possible to analyze these outcomes. The studies were too short in duration to assess side effects. Aliskiren did not increase death, non-fatal serious adverse events or withdrawal due to side effects. The most common adverse events observed were headache, diarrhoea, dizziness and fatigue. Diarrhoea was considerably increased with aliskiren 600 mg as compared to placebo. The decrease in blood pressure at the recommended dose was rated as moderate-quality evidence and adverse event data was graded as low-quality evidence as included studies were assessed to have high likelihood of reporting and funding bias.

10.1002/14651858.CD007066.pub3

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cochrane-simplification-train-2371

Three cross-over and two parallel trials were included with a total of 246 participants. The methodological quality of all studies was unclear. As the trials tested different comparisons, or had a different design or dealt with different outcome measures, meta-analysis was not performed. In one cross-over trial (10 participants) femoxetine had no significant effect in eliminating or reducing EDS but significantly reduced cataplexy. Mild and transient side effects were reported in the femoxetine treatment period by two participants. In a second cross-over trial (56 participants) viloxazine significantly reduced EDS and cataplexy. In a third cross-over trial the authors inappropriately treated the trial design as a parallel study and no conclusions can be reached in favour of either drug. Two more trials with parallel design tested ritanserin versus placebo without finding differences of effectiveness in reducing EDS or cataplexy. Since the last version of this review no new studies were found. There was no good quality evidence that antidepressants are effective for narcolepsy or improve quality of life. Despite the clinical consensus recommending antidepressants for cataplexy there is scarce evidence that antidepressants have a positive effect on this symptom. There is a clear need for well-designed randomised controlled trials to assess the effect of antidepressants on narcolepsy.

Five trials with 246 participants were included. There is no evidence that antidepressants have a beneficial effect on narcolepsy. Moreover, despite the clinical consensus recommending their use for cataplexy, there is scarce evidence to support the use of antidepressant drugs to treat this symptom.

10.1002/14651858.CD003724.pub3

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cochrane-simplification-train-2372

Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026). In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007). The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.

The review authors identified only two small randomised controlled trials with a combined total of 57 participants testing the safety and effectiveness of this treatment. The findings were inconsistent. In one trial, pain at rest, pain-free walking distance, ankle brachial blood pressure index, and the number of amputations all clearly improved in the group receiving mononuclear cell implantation. In the other trial only the number of amputations showed a significant improvement in the treatment group compared with the control group. No deaths were reported during the study period. Quality of the evidence The two included studies differed from each other in how they obtained the cells for injection and assessed the clinical effects at different time points, up to three months in one trial, and six months in the other. They were classified as having a moderate risk of bias with unclear issues regarding their methods and the overall quality of the evidence was considered moderate.

10.1002/14651858.CD008347.pub3

cochrane-simplification-train-2373

cochrane-simplification-train-2373

Twelve studies (1187 participants) were included in the review. Risk of bias was unclear for the majority of domains in each study. Uric acid lowering therapy may make little or no difference in death at six months (2 studies, 498 participants: RR 1.66, 95% CI 0.61 to 4.48) or two years (2 studies, 220 participants): RR 0.13, 95% CI 0.02 to 1.06) (low certainty evidence). Uric acid lowering therapy may make little of no difference (low certainty evidence) in the incidence of ESKD at one or two years. Kidney function may be improved by uric acid lowering therapy at one year with a reduction in serum creatinine (2 studies, 83 participants: MD -73.35 µmol/L, 95% CI -107.28 to -39.41) and a rise in eGFR (1 study, 113 participants: MD 5.50 mL/min/1.73 m2, 95% CI 0.59 to 10.41). However it probably makes little or no difference to eGFR at two years (2 studies, 164 participants: MD 4.00 mL/min, 95% CI -3.28 to 11.28). Uric acid lowering therapy reduced uric acid levels at all time points (3, 4, 6, 12 and 24 months) (high certainty evidence). There is insufficient evidence to support an effect on blood pressure, proteinuria or other cardiovascular markers by uric acid lowering therapy. It should be noted that the apparent benefits of treatment were not apparent at all time points, introducing the potential for bias. There is limited data which suggests uric acid lowering therapy may prevent progression of chronic kidney disease but the conclusion is very uncertain. Benefits were not observed at all time points and study quality was generally low. Larger studies are required to study the effect of uric acid lowering therapy on CKD progression. Three ongoing studies will hopefully provide much needed high quality data.

The quality of the included studies was difficult to grade due to a lack of information. These are not, therefore, high quality studies. We found a small amount of evidence that reducing uric acid levels may slow down damage to kidneys but no evidence that it improves blood pressure or any of the other cardiovascular markers that were investigated. The number of patients requiring dialysis treatment for complete kidney failure appears unchanged. Two measures of kidney failure (serum creatinine and glomerular filtration rate) were improved at six and 12 months but not at two years. The amount of protein in the urine was also reduced by treatment. We found no clear effect on death, blood pressure, rates of hospitalisation, or side effects of treatment. There is limited data which suggests urate lowering therapy may slow down damage to the kidneys but the conclusion is very uncertain. Benefits were not observed at all time points and study quality was generally low. Larger studies are required to study the effect of uric acid lowering therapy on CKD progression.

10.1002/14651858.CD009460.pub2

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cochrane-simplification-train-2374

The update search September 2014 found no further new studies for inclusion, the number of studies included in this review remains eight with a total of 1144 participants. Our main outcomes of interest are hospital use, global state, mental state, quality of life, participant satisfaction and family burden. With the exception of mental state, it was not possible to pool data for these outcomes. Crisis intervention may reduce repeat admissions to hospital (excluding index admissions) at six months (1 RCT, n = 369, RR 0.75 CI 0.50 to 1.13, high quality evidence), but does appear to reduce family burden (at six months: 1 RCT, n = 120, RR 0.34 CI 0.20 to 0.59, low quality evidence), improve mental state (Brief Psychiatric Rating Scale (BPRS) three months: 2 RCTs, n = 248, MD -4.03 CI -8.18 to 0.12, low quality evidence), and improve global state (Global Assessment Scale (GAS) 20 months; 1 RCT, n = 142, MD 5.70, -0.26 to 11.66, moderate quality evidence). Participants in the crisis-intervention group were more satisfied with their care 20 months after crisis (Client Satisfaction Questionnaire (CSQ-8): 1 RCT, n = 137, MD 5.40 CI 3.91 to 6.89, moderate quality evidence). However, quality of life scores at six months were similar between treatment groups (Manchester Short Assessment of quality of life (MANSA); 1 RCT, n = 226, MD -1.50 CI -5.15 to 2.15, low quality evidence). Favourable results for crisis intervention were also found for leaving the study early and family satisfaction. No differences in death rates were found. Some studies suggested crisis intervention to be more cost-effective than hospital care but all numerical data were either skewed or unusable. We identified no data on staff satisfaction, carer input, complications with medication or number of relapses. Care based on crisis-intervention principles, with or without an ongoing homecare package, appears to be a viable and acceptable way of treating people with serious mental illnesses. However only eight small studies with unclear blinding, reporting and attrition bias could be included and evidence for the main outcomes of interest is low to moderate quality. If this approach is to be widely implemented it would seem that more evaluative studies are still needed.

The review, however, looks at only eight studies. The methods of most of these studies were considered poor and there was no definitive description of crisis intervention or crisis care for studies included before 2006, meaning there was a lack of focus on crisis care in its pure form. Most studies excluded service users with alcohol or drug misuse, and those who were a danger of being harmful to themselves or others. The authors of the review suggest more studies are needed to create a stronger evidence base. Crisis care may be currently delivered without sound and good quality evidence. For example, no data or information were available on carer input, concordance or the willingness of service users to take medication and the number of relapses experienced by service users. Finally, despite reports of staff 'burn-out', staff satisfaction with crisis care was not assessed. This plain language summary has been prepared by Ben Gray, Senior Peer Researcher, McPin Foundation (. http://mcpin.org/).

10.1002/14651858.CD001087.pub5

cochrane-simplification-train-2375

cochrane-simplification-train-2375

The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design, methods, and efficacy outcome reporting. No statistical comparison was undertaken. Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours. Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg. There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence). There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.

For some medicines there were no published trials. For other medicines there was inadequate information. For some medicines, there was adequate information, but the results could be overturned by just a few unpublished studies in which there was no effect. None of these could be regarded as reliable. There remained 53 pairs of medicine and dose with reliable evidence. The range of results with single dose analgesics in participants with moderate or severe acute pain was from 7 out of 10 (70%) achieving good pain relief with the best medicine to about 3 out of 10 (30%) with the worst medicine. No medicine produced high levels of pain relief in all participants. The period over which pain was relieved also varied, from about two hours to about 20 hours. Good results were found for medicines combined in a fixed dose in a single tablet, or medicines made for rapid absorption from the stomach. Commonly used analgesic medicines at the recommended or licensed doses produce good pain relief in many, but not all, people with acute pain. The reasons for this are varied, but people in pain should not be surprised if medicines they are given do not work for them. Alternative analgesic medicines or methods should be found that do work.

10.1002/14651858.CD008659.pub3

cochrane-simplification-train-2376

cochrane-simplification-train-2376

Eight primary studies, including 570 participants, were included. The overall methodological quality of studies was good. Significant clinical heterogeneity resulting from differences in participants and interventions, as well as variation in outcome measures, limited the validity of comparisons between studies for most outcomes. Data for the primary outcome of clinical cure or significant (> 70%) improvement were available for only three studies, which were too heterogeneous to pool. Similarly, heterogeneity in study characteristics limited the validity of meta-analysis for the secondary outcomes of proportion of participants with clinical cure or over 50% reduction in cough severity measure and clinical cure. One parallel group trial of chronic cough which identified a significant treatment effect contributed the majority of statistical heterogeneity for these outcomes. While ICS treatment resulted in a mean decrease in cough score of 0.34 standard deviations (SMD -0.34; 95% CI -0.56 to -0.13; 346 participants), the quality of evidence was low. Heterogeneity also prevented meta-analysis for the outcome of mean change in visual analogue scale score. Meta-analysis was not possible for the outcomes of pulmonary function, complications of cough or biomarkers of inflammation due to insufficient data. There was moderate quality evidence that treatment with ICS did not significantly increase the odds of experiencing an adverse event (OR 1.67; 95% CI 0.92 to 3.04). The studies were highly heterogeneous and results were inconsistent. Heterogeneity in study design needs to be addressed in future research in order to test the efficacy of this intervention. International cough guidelines recommend that a trial of ICS should only be considered in patients after thorough evaluation including chest X-ray and consideration of spirometry and other appropriate investigations.

We found eight studies on 570 people with cough lasting over three weeks. Studies included different types of participants in terms of age, duration of coughing and risk factors for cough. Studies also varied in types of ICS, doses, treatment lengths and types of inhaler used. Cough severity was measured using different scales. We looked at the proportion of people who were clinically cured or showed a significant improvement in cough severity as our primary outcome, but the data were too mixed to be able draw any conclusions. These differences between studies also prevented meaningful pooling of study results for proportion of people showing improvement in cough and average improvement in one specific type of cough scale. There was low quality evidence that ICS reduced cough severity score. There was not enough data about changes in pulmonary function, complications of cough and markers of inflammation to allow pooling of results.There was evidence of moderate quality that ICS treatment did not increase the risk of adverse events. This review has shown that the effects of ICS for subacute and chronic cough are inconsistent. Further studies with more consistent patient populations, interventions, outcome measures and reporting are needed to determine whether ICS help subacute and chronic cough in adults. This Cochrane plain language summary was written in December 2012.

10.1002/14651858.CD009305.pub2

cochrane-simplification-train-2377

cochrane-simplification-train-2377

We included 33 studies enrolling 2056 participants. Twenty-six new studies were added to this 2019 update. Seven studies originally excluded from the 2005 review were included as they met the updated review eligibility criteria, which have been expanded to include RCTs in which participants did not meet criteria for depression as an inclusion criterion. Psychosocial interventions included acupressure, cognitive-behavioural therapy, counselling, education, exercise, meditation, motivational interviewing, relaxation techniques, social activity, spiritual practices, support groups, telephone support, visualisation, and voice-recording of a psychological intervention. The duration of study follow-up ranged between three weeks and one year. Studies included between nine and 235 participants. The mean study age ranged between 36.1 and 73.9 years. Random sequence generation and allocation concealment were at low risk of bias in eight and one studies respectively. One study reported low risk methods for blinding of participants and investigators, and outcome assessment was blinded in seven studies. Twelve studies were at low risk of attrition bias, eight studies were at low risk of selective reporting bias, and 21 studies were at low risk of other potential sources of bias. Cognitive behavioural therapy probably improves depressive symptoms measured using the Beck Depression Inventory (4 studies, 230 participants: MD -6.10, 95% CI -8.63 to -3.57), based on moderate certainty evidence. Cognitive behavioural therapy compared to usual care probably improves HRQoL measured either with the Kidney Disease Quality of Life Instrument Short Form or the Quality of Life Scale, with a 0.5 standardised mean difference representing a moderate effect size (4 studies, 230 participants: SMD 0.51, 95% CI 0.19 to 0.83) , based on moderate certainty evidence. Cognitive behavioural therapy may reduce major depression symptoms (one study) and anxiety, and increase self-efficacy (one study). Cognitive behavioural therapy studies did not report hospitalisation. We found low-certainty evidence that counselling may slightly reduce depressive symptoms measured with the Beck Depression Inventory (3 studies, 99 participants: MD -3.84, 95% CI -6.14 to -1.53) compared to usual care. Counselling reported no difference in HRQoL (one study). Counselling studies did not measure risk of major depression, suicide, or hospitalisation. Exercise may reduce or prevent major depression (3 studies, 108 participants: RR 0.47, 95% CI 0.27 to 0.81), depression of any severity (3 studies, 108 participants: RR 0.69, 95% CI 0.54 to 0.87) and improve HRQoL measured with Quality of Life Index score (2 studies, 64 participants: MD 3.06, 95% CI 2.29 to 3.83) compared to usual care with low certainty. With moderate certainty, exercise probably improves depression symptoms measured with the Beck Depression Inventory (3 studies, 108 participants: MD -7.61, 95% CI -9.59 to -5.63). Exercise may reduce anxiety (one study). No exercise studies measured suicide risk or withdrawal from dialysis. We found moderate-certainty evidence that relaxation techniques probably reduce depressive symptoms measured with the Beck Depression Inventory (2 studies, 122 participants: MD -5.77, 95% CI -8.76 to -2.78). Relaxation techniques reported no difference in HRQoL (one study). Relaxation studies did not measure risk of major depression or suicide. Spiritual practices have uncertain effects on depressive symptoms measured either with the Beck Depression Inventory or the Brief Symptom Inventory (2 studies, 116 participants: SMD -1.00, 95% CI -3.52 to 1.53; very low certainty evidence). No differences between spiritual practices and usual care were reported on anxiety (one study), and HRQoL (one study). No study of spiritual practices evaluated effects on suicide risk, withdrawal from dialysis or hospitalisation. There were few or no data on acupressure, telephone support, meditation and adverse events related to psychosocial interventions. Cognitive behavioural therapy, exercise or relaxation techniques probably reduce depressive symptoms (moderate-certainty evidence) for adults with ESKD treated with dialysis. Cognitive behavioural therapy probably increases health-related quality of life. Evidence for spiritual practices, acupressure, telephone support, and meditation is of low certainty . Similarly, evidence for effects of psychosocial interventions on suicide risk, major depression, hospitalisation, withdrawal from dialysis, and adverse events is of low or very low certainty.

We are moderately certain that CBT, exercise, and relaxation techniques probably decrease symptoms of depression for patients treated with long-term dialysis. Counselling may slightly decrease depression symptoms, while we are uncertain whether acupressure, telephone support, or meditation make any difference. We found moderate certainty evidence that CBT provides higher quality of life for dialysis patients. Studies did not measure effects of psychosocial treatments on major depression, suicide risk, and whether therapies made any difference to anxiety, hospital admissions, or withdrawal from dialysis treated is uncertain. Adverse events from treatment is very uncertain. Some study authors did not report the methods for their studies clearly, so we could not be certain whether patients truly had a random chance of being in each treatment group or whether the trial results were assessed by people knowing which treatments that patients actually received. For most outcomes, we identified very few studies, which decreased our confidence in the results. CBT, exercise, and relaxation techniques probably decrease depressive symptoms for dialysis patients while CBT also improves life quality. Counselling may slightly reduce depression among those receiving dialysis. We are not certain whether interventions prevent or treat major depression, anxiety, suicide risk, or withdrawal from dialysis care before death or whether psychological and social treatments have adverse effects.

10.1002/14651858.CD004542.pub3

cochrane-simplification-train-2378

cochrane-simplification-train-2378

The five randomised trials included in the review involved only 428 elderly patients. One small and potentially biased trial of 23 patients with undisplaced intracapsular fracture showed a reduced risk of non-union for those fractures treated operatively. The four trials on extracapsular fractures tested a variety of surgical techniques and implant devices and only one trial involving 106 patients can be considered to test current practice. In this trial, no differences were found in medical complications, mortality and long-term pain. However, operative treatment was more likely to result in the fracture healing without leg shortening, a shorter hospital stay and a statistically non-significant increase in the return of patients back to their original residence. Although there is a lack of available evidence to inform practice for undisplaced intracapsular fractures, variation in practice has reduced and most fractures are treated surgically. The limited available evidence from randomised trials does not suggest major differences in outcome between conservative and operative management programmes for extracapsular femoral fractures, but operative treatment is associated with a reduced length of hospital stay and improved rehabilitation. Conservative treatment will be acceptable where modern surgical facilities are unavailable, and will result in a reduction in complications associated with surgery, but rehabilitation is likely to be slower and limb deformity more common. Currently, it is difficult to conceive circumstances in which future trials would be practical or viable.

The five randomised trials included in the review involved only 428 elderly patients. One small and potentially biased trial of 23 patients with undisplaced intracapsular fracture provided limited evidence that surgical fixation increased the chances of the fracture healing. The four trials on extracapsular fractures tested a variety of surgical techniques and implant devices and only one trial involving 106 patients can be considered to test current practice. This trial found no major difference between surgery and traction for people with extracapsular fractures. However, people who had surgery had better anatomical outcomes, tended to leave hospital sooner, and seemed less likely to lose their independence. The review concluded that overall there was insufficient evidence to determine if surgery is better than bed rest and traction for the two categories of hip fractures tested in randomised trials. However, nowadays most people with hip fracture are treated surgically where it is safe to do so. This reflects advances in surgery and anaesthesia and a clearer understanding of the benefits of early mobilisation and of the risks of prolonged hospital stay.

10.1002/14651858.CD000337.pub2

cochrane-simplification-train-2379

cochrane-simplification-train-2379

We included 38 trials involving 2728 participants. Results are based on individual studies or limited pooled analyses. There was good evidence in: Leishmania braziliensis and L. panamensis infections: Intramuscular (IM) meglumine antimoniate (MA) was better than oral allopurinol for 28 days (1RCT n=127, RR 0.39; 95% CI 0.26, 0.58). Intravenous (IV)MA for 20-days was better than 3-day and 7-day IVMA plus 15% paromomycin plus 12% methylbenzethonium chloride (PR-MBCL) or 7-day IVMA (1RCT n= 150, RR 0.24; 95% CI 0.11, 0.50; RR 0.69; 95% CI 0.53, 0.90; RR 0.64; 95% CI 0.44, 0.92 respectively). Oral allopurinol plus antimonials was better than IV antimonials (2RCT n= 168, RR 1.90; 95% CI 1.40, 2.59; I2=0%). L. braziliensis infections: Oral pentoxifylline plus IV sodium stibogluconate (SSG) was better than IVSSG (1RCT n= 23, RR 1.66; 95% CI 1.03, 2.69); IVMA was better than IM aminosidine sulphate (1RCT n= 38, RR 0.05; 95% CI 0.00, 0.78) and better than IV pentamidine isethionate (1RCT n= 80, RR 0.45; 95% CI 0.29, 0.71). Intramuscular MA was better than Bacillus Calmette-Guérin (1RCT n= 93, RR 0.46; 95% CI 0.32, 0.65). L .panamensis infections: Oral allopurinol was better than IVMA (1RCT n= 58, RR 2.20; 95% CI 1.34, 3.60). Aminosidine sulphate at doses of 12mg/kg/day and 18mg/kg/day for 14 days were better than aminosidine sulphate 12mg/kg/day for 7 days (1RCT n= 60, RR 0.23; 95% CI 0.07, 0.73; RR 0.23; 95% CI 0.07, 0.73 respectively). Oral ketoconazole for 28 days, oral miltefosine and topical PR-MBCL were better than placebo. Most trials have been designed and reported so poorly that they are inconclusive. There is a need for large well conducted studies that evaluate long-term effects of current therapies to improve quality and standardization of methods.

There was reasonable randomised controlled trial (RCT) evidence in L. braziliensis infections that oral pentoxifylline plus IVSSG was better than IVSSG alone; IVMA was better than IM aminosidine sulphate and IV pentamidine isethionate; and IMMA was better than the Bacillus Calmette-Guérin vaccine. Regarding L. panamensis infections, oral ketoconazole for 28 days and oral miltefosine and topical PR-MBCL were all better than placebo; oral allopurinol better than IVMA, aminosidine sulphate 12mg/kg/day and 18mg/kg/day for 14 days were better than aminosidine sulphate 12mg/kg/day for 7 days. There was complete absence of RCT evidence on alternative treatments, surgery, oral itraconazole and fluconazole, oral antibiotics like rifampicin, metronidazole and cotrimoxazole, intravenous or topical amphotericin B, oral dapsone, photodynamic therapy, promoting healing therapies, laser, and cryotherapy treatments. Moreover, none of the studies reported quality of life, "microbiological or histopathological cure of skin lesions", changes in ability to detect the parasite by diagnostic methods (e.g. smear or culture) or mortality. No general consensus on optimal treatment has been achieved but alternatives to intramuscular or intravenous treatments are under active investigation. The evidence base for the treatment of American cutaneous and mucocutaneous leishmaniasis has many limitations due to poor design and reporting of clinical trials. Because resources are limited for clinical research into neglected diseases, there is a need for prioritising properly designed clinical trials. Therefore, we suggest the creation of an international strategy to improve the quality and standardization of future trials for a better evidence-based strategic approach in the future.

10.1002/14651858.CD004834.pub2

cochrane-simplification-train-2380

cochrane-simplification-train-2380

In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti-IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving background inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab-treated participants compared with those given placebo (weighted mean difference (WMD) -118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI -154 to -84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta2-agonist medication compared with placebo (mean difference (MD) -0.39 puffs per day, 95% CI -0.55 to -0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD -0.58, 95% CI -0.84 to -0.31) and severe (MD -0.30, 95% CI -0.49 to -0.10) asthma subgroups on a background therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a background therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double-dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone-sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research.

Twenty-five studies, involving 6382 people, were included in this review. These studies lasted between eight and 60 weeks. All of the people included in the studies had asthma, of different severity. Both men and women were included, and some of the studies included children and young people. All studies compared omalizumab versus placebo. In keeping with current medical practice, most studies (21 of 25) used omalizumab given by injection under the skin. Some of the older studies used omalizumab injected into a vein or given by inhalation. The evidence presented here is current to June 2013. Most of the studies were sponsored by the pharmaceutical industry. We found that people receiving omalizumab were less likely to have a flare-up (‘exacerbation’) of their asthma. For example, on average, 26 of 100 people who were receiving placebo (over a 16 to 60-week period) had an exacerbation compared with an average of 16 of 100 people receiving omalizumab. People receiving omalizumab were also more likely to be able to reduce the doses of inhaled steroids. For example, on average, 21 of 100 people with moderate or severe asthma who were receiving placebo were able to completely stop their inhaled steroids (over a 28 to 32-week period) compared with an average of 40 of 100 receiving omalizumab. People receiving omalizumab also experienced improvement in their asthma symptoms and in their health-related quality of life. People receiving omalizumab were no more or less likely to have unwanted side effects overall. However, people receiving omalizumab were more likely to have skin reactions at the site of the injection. Perhaps unfortunately, many of the trials in this review included participants with moderate asthma, and this drug is not licenced for this group. More trials need to focus on whether this drug is effective in people with the most severe asthma; evidence for efficacy in this group is poor, in spite of current guidelines. The evidence presented in this review is generally of moderate quality. Most of the studies did not clearly explain how investigators decided which people would receive omalizumab and which would receive placebo, and this decision is an important part of well-conducted studies.

10.1002/14651858.CD003559.pub4

cochrane-simplification-train-2381

cochrane-simplification-train-2381

Twelve studies, assessed as high (six) and unclear (six) risk of bias, comprising 689 participants (830 fractures), were included. Interventions examined different plate materials and morphology; use of one or two lag screws; microplate versus miniplate; early and delayed mobilization; eyelet wires versus Rapid IMF™ and the management of angle fractures with intraoral access alone or combined with a transbuccal approach. Patient-oriented outcomes were largely ignored and post-operative pain scores were inadequately reported. Unfortunately, only one or two trials with small sample sizes were conducted for each comparison and outcome. Our results and conclusions should therefore be interpreted with caution. We were able to pool the results for two comparisons assessing one outcome. Pooled data from two studies comparing two miniplates versus one miniplate revealed no significant difference in the risk of post-operative infection of surgical site (risk ratio (RR) 1.32, 95% CI 0.41 to 4.22, P = 0.64, I2 = 0%). Similarly, no difference in post-operative infection between the use of two 3-dimensional (3D) and standard (2D) miniplates was determined (RR 1.26, 95% CI 0.19 to 8.13, P = 0.81, I2 = 27%). The included studies involved a small number of participants with a low number of events. This review illustrates that there is currently inadequate evidence to support the effectiveness of a single approach in the management of mandibular fractures without condylar involvement. The lack of high quality evidence may be explained by clinical diversity, variability in assessment tools used and difficulty in grading outcomes with existing measurement tools. Until high level evidence is available, treatment decisions should continue to be based on the clinician's prior experience and the individual circumstances.

The evidence on which this review is based is up to date as of 28 February 2013. Twelve studies with a combined total of 689 participants were included in this review. Participants ranged in age from 16 to 68 years and most participants (90%) were male. All of the studies compared different types of surgical treatments, and each study evaluated a different aspect of surgical treatment such as different types of plates, screws, or wires or how long the jaw was immobilized after surgery. There were concerns about the design and quality of all the studies. All the studies evaluated different aspects of surgical treatment. None of the studies evaluated non-surgical treatments such as intermaxillary fixation and no study compared surgical treatment with non-surgical treatment. As a result there is no clear evidence to indicate which approach is the best to manage these fractures. The quality of the evidence found is poor. Recommendations are made for further well-conducted research studies in this area to be undertaken.

10.1002/14651858.CD006087.pub3

cochrane-simplification-train-2382

cochrane-simplification-train-2382

Seven studies, 492 participants, met the inclusion criteria Disulfiram versus placebo: no statistically significant results for dropouts but a trend favouring disulfiram, two studies, 87 participants, RR 0.82 (95% CI 0.66 to 1.03). One more study, 107 participants, favouring disulfiram, was excluded from meta-analysis due high heterogeneity, RR 0.34 (95% CI 0.20 to 0.58). For cocaine use, it was not possible to pool together primary studies, results from single studies showed that, one, out of four comparisons, was in favour of disulfiram (number of weeks abstinence, 20 participants, WMD 4.50 (95% CI 2.93 to 6.07). Disulfiram versus naltrexone: no statistically significant results for dropouts but a trend favouring disulfiram, three studies, 131 participants, RR 0.67 (95% CI 0.45 to 1.01). No significant difference for cocaine use was seen in the only study that considered this outcome. Disulfiram versus no pharmacological treatment: for cocaine use: a statistically significant difference in favour of disulfiram, one study, two comparisons, 90 participants: maximum weeks of consecutive abstinence, WMD 2.10 (95% CI 0.69 to 3.51); number of subjects achieving 3 or more weeks of consecutive abstinence, RR 1.88 (95% CI 1.09 to 3.23). There is low evidence, at the present, supporting the clinical use of disulfiram for the treatment of cocaine dependence. Larger randomised investigations are needed investigating relevant outcomes and reporting data to allow comparisons of results between studies. Results from ongoing studies will be added as soon as their results will be available.

Disulfiram showed a trend toward fewer dropouts from psychosocial treatment when compared to placebo (three trials) or naltrexone (three trials) but this was not statistically significant. Assessing cocaine use, single studies were in favour of disulfiram on number of weeks of abstinence in one out of four comparisons when compared with placebo and on maximum weeks of consecutive abstinence and number of people achieving three or more weeks of consecutive abstinence in one study comparing disulfiram to no pharmacological treatment. The included studies did not specifically investigate the adverse effects of disulfiram itself or its potential to increase alcohol and cocaine adverse effects.

10.1002/14651858.CD007024.pub2

cochrane-simplification-train-2383

cochrane-simplification-train-2383

We included three RCTs in which a total of 77 women took part. We rated the quality of the evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision. We performed a meta-analysis of two trials with 59 participants. When metformin was compared with megestrol acetate in women with endometrial hyperplasia, we found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (odds ratio (OR) 3.34, 95% confidence interval (CI) 0.97 to 11.57, two RCTs, n = 59, very low-quality evidence), hysterectomy rates (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 59, very low-quality evidence), and rates of abnormal uterine bleeding (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 44 , very low-quality evidence). We found no data for recurrence of endometrial hyperplasia or health-related quality of life. Both studies (n = 59) provided data on progression of endometrial hyperplasia to endometrial cancer as well as one (n = 16) reporting some adverse effects in the metformin arm, notably nausea, thrombosis, lactic acidosis, abnormal liver and renal function among others. Another trial including 16 participants compared metformin plus megestrol acetate versus megestrol acetate alone in women with endometrial hyperplasia. We found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (OR 9.00, 95% CI 0.94 to 86.52, one RCT, n = 16, very low-quality evidence), recurrence of endometrial hyperplasia among women who achieve regression (OR not estimable, no events recorded, one RCT, n = 8, very low-quality evidence), progression of endometrial hyperplasia to endometrial cancer (OR not estimable, no events recorded, one RCT, n = 13, very low-quality evidence), or hysterectomy rates (OR 0.29, 95% CI 0.01 to 8.37, one RCT, n = 16, very low-quality evidence). Investigators provided no data on abnormal uterine bleeding or health-related quality of life. In terms of adverse effects, three of eight participants (37.5%) in the metformin plus megestrol acetate study arm reported nausea. At present, evidence is insufficient to support or refute the use of metformin alone or in combination with standard therapy - specifically, megestrol acetate - versus megestrol acetate alone, for treatment of endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials yielding long-term outcome data are needed to address this clinical question.

We included three randomised controlled trials in which a total of 77 women took part. Two studies compared metformin versus megestrol acetate (a form of progesterone), and one study compared metformin plus megestrol acetate versus megestrol acetate alone. Women in all studies received treatment for approximately 12 weeks. The evidence is current to 10 January 2017. Comparisons of metformin versus megestrol acetate have provided insufficient evidence to show differences in effectiveness for curing endometrial hyperplasia. It remains uncertain whether there is any difference between metformin and megestrol acetate in reducing hysterectomy rates or abnormal uterine bleeding in women with endometrial hyperplasia. Although both studies provided data on progression of endometrial hyperplasia to endometrial cancer, there were no events in either arm, and study authors reported no data on adverse effects. When metformin plus megestrol acetate is compared with megestrol acetate, differences in effectiveness between groups treating endometrial hyperplasia remain unclear. Three of eight patients in the metformin plus megestrol acetate study arm reported nausea. Occurrence of other adverse events is unclear. We rated the quality of evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision.

10.1002/14651858.CD012214.pub2

cochrane-simplification-train-2384

cochrane-simplification-train-2384

This updated review includes two additional studies (and 976 additional participants), for a total of seven parallel-group RCTs and 1550 participants, 66% of whom were male. Participants' mean age was 68 years and was similar among studies. Airflow obstruction was moderately severe in three studies and severe in four studies; mean post bronchodilator forced expiratory volume in one second (FEV1) was 54% predicted, and 27% of participants were current smokers. Four studies prepared individualised action plans, one study an oral plan and two studies standard written action plans. All studies provided short educational input on COPD, and two studies supplied ongoing support for action plan use. Follow-up was 12 months in four studies and six months in three studies. When compared with usual care, an action plan with phone call follow-up significantly reduced the combined rate of hospitalisations and emergency department (ED) visits for COPD over 12 months in one study with 743 participants (rate ratio (RR) 0.59, 95% confidence interval (CI) 0.44 to 0.79; high-quality evidence), but the rate of hospitalisations alone in this study failed to achieve statistical significance (RR 0.69, 95% CI 0.47 to 1.01; moderate-quality evidence). Over 12 months, action plans significantly decreased the likelihood of hospital admission (odds ratio (OR) 0.69, 95% CI 0.49 to 0.97; n = 897; two RCTs; moderate-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) 19 (11 to 201)) and the likelihood of an ED visit (OR 0.55, 95% CI 0.38 to 0.78; n = 897; two RCTs; moderate-quality evidence; NNTB over 12 months 12 (9 to 26)) compared with usual care. Results showed no significant difference in all-cause mortality during 12 months (OR 0.88, 95% CI 0.59 to 1.31; n = 1134; four RCTs; moderate-quality evidence due to wide confidence interval). Over 12 months, use of oral corticosteroids was increased with action plans compared with usual care (mean difference (MD) 0.74 courses, 95% CI 0.12 to 1.35; n = 200; two RCTs; moderate-quality evidence), and the cumulative prednisolone dose was significantly higher (MD 779.0 mg, 95% CI 533.2 to 10248; n = 743; one RCT; high-quality evidence). Use of antibiotics was greater in the intervention group than in the usual care group (subgrouped by phone call follow-up) over 12 months (MD 2.3 courses, 95% CI 1.8 to 2.7; n = 943; three RCTs; moderate-quality evidence). Subgroup analysis by ongoing support for action plan use was limited; review authors noted no subgroup differences in the likelihood of hospital admission or ED visits or all-cause mortality over 12 months. Antibiotic use over 12 months showed a significant difference between subgroups in studies without and with ongoing support. Overall quality of life score on St George’s Respiratory Questionnaire (SGRQ) showed a small improvement with action plans compared with usual care over 12 months (MD -2.8, 95% CI -0.8 to -4.8; n = 1009; three RCTs; moderate-quality evidence). Low-quality evidence showed no benefit for psychological morbidity as measured with the Hospital Anxiety and Depression Scale (HADS). Use of COPD exacerbation action plans with a single short educational component along with ongoing support directed at use of the action plan, but without a comprehensive self-management programme, reduces in-hospital healthcare utilisation and increases treatment of COPD exacerbations with corticosteroids and antibiotics. Use of COPD action plans in this context is unlikely to increase or decrease mortality. Whether additional benefit is derived from periodic ongoing support directed at use of an action plan cannot be determined from the results of this review.

We found seven relevant studies of 1550 people with COPD. We did not include studies that gave other treatments, such as an exercise programme or longer educational sessions, along with an action plan. People in three studies had ongoing support to help them use the action plan. People in the included studies had moderate to severe symptoms and were followed up for six or 12 months. Key results People with COPD who are given an action plan have fewer emergency department visits and hospital stays related to breathing problems over a year. We calculated that for every 19 people given an action plan, one person would avoid a hospital stay for an exacerbation. People with an action plan took more corticosteroid and antibiotic medicines for exacerbations - on average just under one more course of corticosteroids and two more courses of antibiotics over a year. Some studies showed that giving people an action plan improved their ability to recognise and self-start treatment for worsening COPD symptoms. Giving people an action plan made no difference in their chance of dying from any cause over a year, but this finding showed some variability. We could not say whether follow-up phone calls added benefit over following an action plan alone. Quality of the evidence The evidence in this review is generally independent and reliable, and we are very or moderately certain about the results. Conclusions We believe that people with COPD should be given an individualised action plan with a short educational component so they can benefit from fewer and shorter hospital stays, better understanding of the need to self-start treatment and appropriate use of medication for exacerbations.

10.1002/14651858.CD005074.pub4

cochrane-simplification-train-2385

cochrane-simplification-train-2385

Twelve trials with a total of 1879 infants fulfilled the inclusion criteria. Four trials compared standard term formula versus donor breast milk and eight compared nutrient-enriched preterm formula versus donor breast milk. Only the five most recent trials used nutrient-fortified donor breast milk. The trials contain various weaknesses in methodological quality, specifically concerns about allocation concealment in four trials and lack of blinding in most of the trials. Most of the included trials were funded by companies that made the study formula. Formula-fed infants had higher in-hospital rates of weight gain (mean difference (MD) 2.51, 95% confidence interval (CI) 1.93 to 3.08 g/kg/day), linear growth (MD 1.21, 95% CI 0.77 to 1.65 mm/week) and head growth (MD 0.85, 95% CI 0.47 to 1.23 mm/week). These meta-analyses contained high levels of heterogeneity. We did not find evidence of an effect on long-term growth or neurodevelopment. Formula feeding increased the risk of necrotising enterocolitis (typical risk ratio (RR) 1.87, 95% CI 1.23 to 2.85; risk difference (RD) 0.03, 95% CI 0.01 to 0.05; number needed to treat for an additional harmful outcome (NNTH) 33, 95% CI 20 to 100; 9 studies, 1675 infants). The GRADE certainty of evidence was moderate for rates of weight gain, linear growth, and head growth (downgraded for high levels of heterogeneity) and was moderate for neurodevelopmental disability, all-cause mortality, and necrotising enterocolitis (downgraded for imprecision). In preterm and LBW infants, moderate-certainty evidence indicates that feeding with formula compared with donor breast milk, either as a supplement to maternal expressed breast milk or as a sole diet, results in higher rates of weight gain, linear growth, and head growth and a higher risk of developing necrotising enterocolitis. The trial data do not show an effect on all-cause mortality, or on long-term growth or neurodevelopment.

We found 12 completed trials (involving 1871 infants). Most trials, particularly those trials conducted more recently, used reliable methods. Evidence is up to date as of 3 May 2019. The combined analysis of data from these trials shows that feeding with formula increases rates of growth during the hospital stay, but is associated with a higher risk of developing the severe gut disorder called 'necrotising enterocolitis'. There is no evidence of an effect on survival or longer-term growth and development. The currently available evidence suggests that feeding preterm infants with artificial formula (rather than donor breast milk when mother's own breast milk is not available) is associated with faster rates of growth, but with a near-doubling of the risk of developing necrotising enterocolitis. Further, larger trials could provide stronger and more precise evidence to help clinicians and families make informed choices about this issue. Currently, four such trials (involving more than 1100 infants) are ongoing internationally, and we plan to include the data from these trials in this review when these become available.

10.1002/14651858.CD002971.pub5

cochrane-simplification-train-2386

cochrane-simplification-train-2386

Two randomised controlled trials including a total of 148 people aged 70 years or over with unstable extracapsular hip fractures in the trochanteric region were identified and included in this review. Both had methodological limitations, including inadequate assessment of longer-term outcome. One trial compared a cemented arthroplasty with a sliding hip screw. This found no significant differences between the two methods of treatment for operating time, local wound complications, mechanical complications, reoperation, mortality or loss of independence of previously independent patients at one year. There was, however, a higher blood transfusion need in the arthroplasty group. The other trial compared a cementless arthroplasty versus a proximal femoral nail. It also found a higher blood transfusion need in the arthroplasty group, together with a greater operative blood loss, and a longer length of surgery. There were no significant differences between the two interventions for mechanical complications, local wound complications, reoperation, general complications, mortality at one year or long-term function. None of the pooled outcome data yielded statistically significant differences between the arthroplasty and internal fixation, with the exception of the significantly higher numbers of participants in the arthroplasty group requiring blood transfusion (relative risk 1.71, 95% confidence interval 1.05 to 2.77). There is insufficient evidence from randomised trials to determine whether replacement arthroplasty has any advantage over internal fixation for extracapsular hip fractures. Further larger well-designed randomised trials comparing arthroplasty versus internal fixation for the treatment of unstable fractures are required.

The two randomised controlled trials included in this review tested arthroplasty versus internal fixation in a total of 148 mainly female and older participants. Both trials had methodological flaws that may affect the validity of their results and there was a general lack of evidence on long-term effects. One of the trials found a longer length of surgery for the arthroplasty and both trials found an increased need for blood transfusion for the arthroplasty. Pooled data from the two trials showed no statistically significant differences between the two procedures for reoperations, wound healing complications or mortality at one year. Neither trial found a significant difference in longer-term function. Overall, the evidence from the two small trials comparing these two approaches for treating extracapsular hip fractures was too limited to make any definite conclusions as to which is better.

10.1002/14651858.CD000086.pub2

cochrane-simplification-train-2387

cochrane-simplification-train-2387

Seven trials recruiting 3123 babies were included in the meta-analysis. Four trials recruiting 765 babies compared CPAP with supportive care and three trials (2364 infants) compared CPAP with mechanical ventilation. Apart from a lack of blinding of the intervention all studies were of low risk of bias. In the comparison of CPAP with supportive care there was a reduction in failed treatment (typical risk ratio (RR) 0.66, 95% confidence interval (CI) 0.45 to 0.98; typical risk difference (RD) −0.16, 95% CI −0.34 to 0.02; 4 studies, 765 infants, very low quality evidence). There was no reduction in bronchopulmonary dysplasia (BPD) or mortality. In trials comparing CPAP with assisted ventilation with or without surfactant, CPAP resulted in a small but clinically significant reduction in the incidence of BPD at 36 weeks, (typical RR 0.89, 95% CI 0.79 to 0.99; typical RD −0.04, 95% CI −0.08 to 0.00; 3 studies, 772 infants, moderate-quality evidence); and death or BPD (typical RR 0.89, 95% CI 0.81 to 0.97; typical RD −0.05, 95% CI −0.09 to 0.01; 3 studies, 1042 infants, moderate-quality evidence). There was also a clinically important reduction in the need for mechanical ventilation (typical RR 0.50, 95% CI 0.42 to 0.59; typical RD −0.49, 95% CI −0.59 to −0.39; 2 studies, 760 infants, moderate-quality evidence); and the use of surfactant in the CPAP group (typical RR 0.54, 95% CI 0.40 to 0.73; typical RD −0.41, 95% CI −0.54 to −0.28; 3 studies, 1744 infants, moderate-quality evidence). There is insufficient evidence to evaluate prophylactic CPAP compared to oxygen therapy and other supportive care. However when compared to mechanical ventilation prophylactic nasal CPAP in very preterm infants reduces the need for mechanical ventilation and surfactant and also reduces the incidence of BPD and death or BPD.

Randomised controlled trials of preterm babies below 32 weeks' gestation or below 1500 grams at birth who were treated with CPAP applied within the first 15 minutes of life compared with babies who were given either (1) routine supportive care such as oxygen therapy or (2) mechanical ventilation. There were a total of seven studies involving 3123 infants. They were generally of moderate quality. Parents and care-givers would have known which treatment group the babies were in, but we judged this not to be important for most outcomes measured. In the four studies (765 babies) comparing CPAP with supportive care, CPAP resulted in fewer infants requiring further breathing assistance but there was considerable inconsistency between the studies. In the three studies (2354 babies) that compared CPAP with assisted ventilation with or without surfactant, CPAP resulted in a small but clinically important reduction in BPD and the combined outcome of BPD and mortality. There was a reduction in the need for mechanical ventilation and the use of surfactant in the CPAP group.

10.1002/14651858.CD001243.pub3

cochrane-simplification-train-2388

cochrane-simplification-train-2388

Four studies with 273 participants were included. All included studies reported clinical outcomes following valvuloplasty. We found no studies investigating other surgical procedures for the treatment of patients with DVI. All included studies investigated primary valve incompetence. We found no trials that investigated the results of surgery for secondary valvular incompetence or the obstructive form of DVI. Because different outcome measures were used, it was not possible to pool the results of included studies. The methodological quality of the included studies was low, mainly because information regarding randomisation and blinding was missing, or because data were incomplete or were presented poorly. Ulcer healing and ulcer recurrence were not reported in one study, and the remaining three studies did not include participants with ulcers or with active ulceration. Three studies reported no significant complications of surgery and no incidence of DVT during follow-up. One study did not report on the occurrence of complications. Clinical changes were assessed by subjective and objective measurements, as specified in the clinical, aetiological, anatomical, and pathophysiological (CEAP) classification score. This requires vascular laboratory measurements of lower limb haemodynamics before and after surgery. Tests include an overall evaluation of venous function with venous refilling time (VRT) or ambulatory venous pressure (AVP). Two small trials comparing external valvuloplasty using limited anterior plication in combination with ligation of incompetent superficial veins against ligation alone (L) showed that ligation plus limited anterior plication produced significant improvement in AVP: The mean difference was -15 mm Hg (95% confidence interval (CI) -20.9 to -9.0) at one year and -15 mm Hg (95% CI -21 to -8.9) at two years. Sustainable statistically significant improvement in AVP and VRT was achieved by ligation and limited anterior plication at 10 years in one study. However, AVP values after surgery remained relatively high, causing its benefit to be questioned. Similarly, another study including participants who were deteriorating preoperatively showed sustained mild clinical improvement for seven years in those subjected to valvuloplasty compared with participants undergoing superficial venous surgery alone. However, this benefit was lost when the condition of participants was stable preoperatively. One small study (n = 40) with grade 3 reflux and no participants with ulcers reported that external valvuloplasty of the femoral vein combined with surgical repair of the superficial venous system improved the haemodynamic status of the lower limbs, restored valvular function more effectively and achieved better outcomes than surgical repair of the superficial venous system alone. No evidence was found for benefit or harm of valvuloplasty in the treatment of patients with DVI secondary to primary valvular incompetence. The individual trials included in this review were small; they used different methods of assessment and overall were of poor quality. They did not include participants with severe DVI. Trials investigating the effects of other surgical procedures on deep veins are needed. Until the findings of such trials become available, the benefit of valvuloplasty remains uncertain.

Deep venous incompetence (DVI) is a problem in the veins that can lead to leg ulcers (sores), pain and swelling. It may be caused by a problem in the valves of the vein, by a blockage of the veins or by a combination of these events. For most people, wearing special compression stockings and treating the ulcers is enough. When this does not ease the problem, surgery is sometimes tried. This review includes four studies with a total of 273 participants. All included studies reported on outcomes following surgical repair of venous valves (valvuloplasty). We did not identify studies investigating other surgical procedures for the treatment of patients with DVI. All included studies investigated primary valve incompetence (when valves do not close properly because of laxity of the vein wall or valve cusps). We found no trials that investigated the results of surgery for secondary valvular incompetence (when valves do not close properly, for example, when valves are damaged as a result of deep vein thrombosis) or for the obstructive form of DVI. As different outcomes were reported, it was not possible to combine the results of these studies. The methodological quality of the included studies was low, mainly because information regarding allocation of treatment and blinding was missing, or because data were incomplete or were poorly presented. Ulcer healing and ulcer recurrence were not reported in one study, and the remaining three studies did not include patients with ulcers or active ulceration. Three studies reported no significant complications of surgery or no incidence of DVT during follow-up. One study did not report on the occurrence of complications. Clinical changes were assessed by subjective and objective measurements, as specified in the clinical, aetiological, anatomical, and pathophysiological (CEAP) classification score. This requires vascular laboratory measurements of lower limb haemodynamics before and after surgery. Tests include an overall evaluation of venous function with venous refilling time (VRT) or ambulatory venous pressure (AVP). Results show improvement in clinical symptoms and muscle pumping function and significant improvement in the haemodynamic status of patients who had external valvuloplasty along with surgery to the superficial venous system. In patients who had surgery to the superficial venous system only, clinical symptoms improved, but no improvement in muscle pumping function was reported. Evidence is not sufficient to show the effects of surgery on the treatment of patients with DVI. The individual trials included in this review have demonstrated possible long-term benefit in certain groups of patients, but these trials were small, used different methods of assessment and overall were of poor quality. They did not include patients with severe DVI. Trials investigating the effects of other surgical procedures on the deep veins are needed. Until evidence from such trials becomes available, conventional conservative measures, such as high compression therapy or elasticated hosiery, remain the treatments of choice.

10.1002/14651858.CD001097.pub3

cochrane-simplification-train-2389

cochrane-simplification-train-2389

The literature search yielded 359 reports of which only one study was identified that met our inclusion criteria and reported relevant clinical endpoints. This study randomised 4110 adult participants with a functioning kidney transplant and elevated homocysteine levels to folic acid plus high dose B multivitamins or low dose multivitamins who were followed for a mean 4.0 years. Despite effectively lowering homocysteine levels) in homocysteine levels at follow-up (MD -4.40 μmol/L, 95% CI -5.98 to -2.82) there was no evidence the intervention impacted on any of the outcomes reported including cardiovascular mortality (RR 0.91, 95% CI 0.69 to 1.20), all-cause mortality (RR 1.04, 95% CI 0.88 to 1.22), myocardial infarction (RR 1.02, 95% CI 0.77 to 1.35), stroke (RR 1.08, 95% CI 0.69 to 1.71), commencement of renal replacement therapy (RR 1.12, 95% CI 0.91 to 1.37) or all reported adverse events (RR 1.02, 95% CI 0.87 to 1.20). There was no evidence the intervention impacted on the primary endpoint of the study, a cardiovascular event composite (RR 0.99, 95% CI 0.85 to 1.15). The study was of high quality. There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients.

The aim of this review was to determine if homocysteine lowering therapies effectively reduce cardiovascular event rates in kidney transplant recipients. A single study was identified that randomised 4110 adult participants with a functioning kidney transplant to homocysteine lowering with folic acid and high dose multivitamins or to low dose multivitamins and followed them for an average of four years. Despite effectively lowering homocysteine levels, there was no evidence of benefit for any of a range of cardiovascular events. Similarly there was no evidence of harm.

10.1002/14651858.CD007910.pub2

cochrane-simplification-train-2390

cochrane-simplification-train-2390

Two new studies incorporating 96 participants were identified in this update and were added to the six previously included studies. A total of eight studies incorporating 399 participants are included in the updated review. The participants were primarily men aged in their mid-thirties who had sustained a severe TBI. No studies included children. The studies were clinically diverse with regard to the interventions, time postinjury and the outcome measures used. At the end of intervention, the mean difference in peak power output was 35.47 watts (W) in favour of fitness training (MD 35.47 W, 95% CI 2.53 to 68.41 W; 3 studies, 67 participants; low-quality evidence). The CIs include both a possible clinically important effect and a possible negligible effect, and there was moderate heterogeneity among the studies. Five of the secondary outcomes had sufficient data at the end of intervention to enable meta-analysis: body composition (SMD 0.29 standard deviations (favouring control), 95% CI -0.22 to 0.79; 2 studies, 61 participants; low-quality evidence), strength (SMD -0.02 (favouring control), 95% CI -0.86 to 0.83; 2 studies, 23 participants; very low-quality evidence), fatigue (SMD -0.32 (favouring fitness training), 95% CI -0.90 to 0.26; 3 studies, 130 participants; very low-quality evidence), depression (SMD -0.43 (favouring fitness training), 95% CI -0.92 to 0.06; 4 studies, 220 participants; very low-quality evidence), and neuromotor function (MD 0.01 m (favouring fitness training), 95% CI -0.25 to 0.27; 2 studies, 109 participants; moderate-quality evidence). It was uncertain whether fitness training was more or less effective at improving these secondary outcomes compared to the control interventions. Quality of life was assessed in three trials, but we did not pool the data because of substantial heterogeneity. Five of the eight included studies had no dropouts from their intervention group and no adverse events were reported in any study. There is low-quality evidence that fitness training is effective at improving cardiorespiratory deconditioning after TBI; there is insufficient evidence to draw any definitive conclusions about the other outcomes. Whilst the intervention appears to be accepted by people with TBI, and there is no evidence of harm, more adequately powered and well-designed studies are required to determine a more precise estimate of the effect on cardiorespiratory fitness, as well as the effects across a range of important outcome measures and in people with different characteristics (e.g. children). In the absence of high quality evidence, clinicians may be guided by pre-exercise screening checklists to ensure the person with traumatic brain injury is safe to exercise, and set training parameters using guidelines established by the American College of Sports Medicine for people who have suffered a brain injury.

We searched for studies in August 2017. We included eight studies, involving 399 adults with traumatic brain injuries, in this review. Most study participants were men in their mid-thirties who had severe brain injuries. We found no studies that included children. The fitness training programmes were conducted in a range of settings including hospital, community and at home. In six of the eight studies all fitness training sessions were supervised. The type of fitness training varied, and included exercising on a fixed cycling machine, in water, on gym equipment such as a treadmill, home-based exercise, and a fitness group in the military. In six of the eight studies the prescribed intensity, duration and frequency of fitness training met the guidelines set by the American College of Sports Medicine. Three of the eight studies, with 67 participants, assessed change in fitness at the end of the treatment programme. Exercise was conducted on a fixed cycling machine in two studies, and in water in the third, and all sessions were supervised. The fitness training was compared to non-exercise interventions in two of these studies, and to no intervention in the third study. We combined the results of the three studies, which demonstrated an average (mean) improvement of 35 watts on an exercise test in the fitness training groups compared to the non-exercise intervention and no intervention groups. This improvement represents approximately a 36% improvement in fitness from the start of the study, which is a large effect. However, this estimate is uncertain and the difference is likely to be between 3 to 68 watts, which may or may not be important clinically. More than one study reported on six other outcomes; body composition, strength, tiredness, depression, quality of life and walking. It was unclear whether fitness training was better or worse than the non-exercise interventions or no intervention at improving these outcomes. Measures of cognition, activities of daily living, and return to everyday activities were only measured in one study, and there were no studies that measured the effect of fitness training on levels of physical activity and motivation. Only three studies examined the effect of fitness training beyond the end of the programme, but these could not provide a clear answer regarding the long-term effects of fitness training. In the five studies that provided supervision for all fitness training sessions, all participants in the fitness training groups completed the studies. Treatment attendance varied between studies, and was reported as ranging from 59% to 100%, and was not reported for two studies. There was no evidence of harm caused by fitness training in any study. Our certainty in these findings is reduced due to the low quality of the evidence caused by small numbers of study participants, poor reporting of some study details, and possible errors in the way some of the studies were carried out. It is unclear whether fitness training after a traumatic brain injury improves physical fitness. There is not enough evidence to understand the effect of fitness training on other important outcomes. Whilst fitness training appears to be well attended by people with traumatic brain injury, particularly when supervised, and there is no evidence of harm, further well-designed studies are required before we can draw any definite conclusions. In the absence of high quality evidence, health professionals may be guided by pre-exercise screening checklists to ensure the person with traumatic brain injury is safe to exercise, and to set training parameters using guidelines established by the American College of Sports Medicine for people who have suffered a brain injury.

10.1002/14651858.CD006123.pub3

cochrane-simplification-train-2391

cochrane-simplification-train-2391

We included in this updated review five RCTs with a total of 403 participants, and we added two new trials identified during the 2015 search. One of the included studies was found to have a high risk of bias; no trial featured all pre-specified outcomes. We found two trials for which data are awaited for classification and one ongoing trial. Three studies compared advanced haemodynamic monitoring with a protocol using standard measures; three compared advanced haemodynamic monitoring with usual care; and one compared a protocol using standard measures with usual care. Meta-analyses for the two advanced haemodynamic monitoring comparisons are consistent with both increased and decreased risk of mortality (RR Mantel-Haenszel (M-H) random-effects 0.41, 95% confidence interval (CI) 0.14 to 1.20; 280 participants; RR M-H random-effects 0.45, 95% CI 0.07 to 2.95; 213 participants, respectively). The study comparing a protocol with usual care found no difference between groups for this outcome. Three studies comparing advanced haemodynamic monitoring with usual care reported data for length of stay and time to medical fitness. There was no statistically significant difference between groups for these outcomes in the two studies that we were able to combine (MD IV fixed 0.63, 95% CI -1.70 to 2.96); MD IV fixed 0.01, 95% CI -1.74 to 1.71, respectively) and no statistically significant difference in the third study. One study reported reduced time to medical fitness when comparing advanced haemodynamic monitoring with a protocol, and when comparing protocol monitoring with usual care. The number of participants with one or more complications showed no statistically significant differences in each of the two advanced haemodynamic monitoring comparisons (RR M-H random-effects 0.83, 95% CI 0.59 to 1.17; 280 participants; RR M-H random-effects 0.72, 95% CI 0.40 to 1.31; 173 participants, respectively), nor any differences in the protocol and usual care comparison. Only one study reported the number of participants able to return to normal accommodation after discharge with no statistically significant difference between groups. There were few studies with a small number of participants, and by using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) approach, we judged the quality of the outcome evidence as low. We had included one study with a high risk of bias, but upon applying GRADE, we downgraded the quality of this outcome evidence to very low. Five studies including a total of 403 participants provided no evidence that fluid optimization strategies improve outcomes for participants undergoing surgery for PFF. Further research powered to test some of these outcomes is ongoing.

Evidence is current to September 2015. We found five studies with 403 participants, each of which compared two or three methods of guiding fluid therapy. These methods include 'usual care' (whereby staff use changes in basic measurements, such as heart rate, to decide for themselves how much fluid to give), 'protocols using standard measures' (whereby staff use changes in basic measurements when giving fluid according to a formal set of rules) and 'advanced haemodynamic monitoring' (whereby staff use invasive equipment, such as specialized blood pressure monitoring devices placed into arteries, to determine how much fluid to give). These trials found no evidence to suggest that using one method instead of another reduces harm, including death, or decreases the number of complications. We found no evidence, when study results were combined, indicating that any method reduced length of hospital stay or time that participants were assessed as medically fit for discharge. Results also showed no difference in the number of participants able to return to normal accommodation after discharge. We found few relevant studies with only a small number of participants. The time difference between the earliest study, published in 1985, and the latest study, published in 2014, suggests that standard practice for managing hip fracture may differ between these studies. We judged one study as having a high risk of bias, and we used the GRADE approach to assess evidence quality as low or very low. Results of the review are applicable only to countries in which the relevant studies were conducted, as 'usual care' may differ in other countries. Current evidence is insufficient to show which method of finding maximum effective fluid levels in people undergoing hip fracture surgery is preferable.

10.1002/14651858.CD003004.pub4

cochrane-simplification-train-2392

cochrane-simplification-train-2392

Six studies met the inclusion criteria. The data obtained were unsuitable for the conduct of a meta-analysis; we have completed a qualitative summary. All studies were found to have high or unclear risk of bias in some aspects of their methodology. Five of the six studies reported data collected in the randomised controlled phase of the study. A sixth study did not report sufficient results to determine the effect of intrathecal baclofen versus placebo. Of these five studies, four were conducted using lumbar puncture or other short-term means of delivering intrathecal baclofen. One study assessed the effectiveness of implantable intrathecal baclofen pumps over six months. The four short-term studies demonstrated that intrathecal baclofen therapy reduces spasticity in children with cerebral palsy. However, two of these studies utilised inappropriate techniques for statistical analysis of results. The single longer-term study demonstrated minimal reduction in spasticity with the use of intrathecal baclofen therapy. One of the short-term studies and the longer term study showed improvement in comfort and ease of care. The longer term study found a small improvement in gross motor function and also in some domains of health-related quality of life. Some caution is required in interpreting the findings of the all the studies in the review due to methodological issues. In particular, there was a high risk of bias in the methodology of the longer term study due to the lack of placebo use in the control group and the absence of blinding to the intervention after randomisation for both participants and investigators. There is some limited short-term evidence that intrathecal baclofen is an effective therapy for reducing spasticity in children with cerebral palsy. The effect of intrathecal baclofen on long-term spasticity outcomes is less certain. The validity of the evidence for the effectiveness of intrathecal baclofen in treating spasticity in children with cerebral palsy from the studies in the review is constrained by the small sample sizes of the studies and methodological issues in some studies. Spasticity is a impairment in the domain of body structure and function. Consideration must also be given to the broader context in determining whether intrathecal baclofen therapy is effective. The aim of therapy may be, for example, to improve gross motor function, to increase participation at a social role level, to improve comfort, to improve the ease of care by others or to improve the overall quality of life of the individual. Intrathecal baclofen may improve gross motor function in children with cerebral palsy, but more reliable evidence is needed to determine this.There is some evidence that intrathecal baclofen improves ease of care and the comfort and quality of life of the individuals receiving it, but again small sample sizes and methodological issues in the studies mean that these results should be interpreted with caution. Further evidence of the effectiveness of intrathecal baclofen for treating spasticity, increasing gross motor function and improving comfort, ease of care and quality of life is needed from other investigators in order to validate these results. The short duration of the controlled studies included in this review did not allow for the exploration of questions regarding whether the subsequent need for orthopaedic surgery in children receiving intrathecal baclofen therapy is altered, or the safety and the economic implications of intrathecal baclofen treatment when long-term therapy is administered via an implanted device. Controlled studies are not the most appropriate study design to address these questions, cohort studies may be more appropriate.

This review concludes that there is a small amount of evidence from studies performed to date that intrathecal baclofen is an effective treatment for reducing spasticity in children with cerebral palsy in the short-term. The effect of intrathecal baclofen on spasticity in children with cerebral palsy over the long term is less clear. Two short-term studies (by the same investigators) demonstrate a reduction in spasticity, but a single, longer term study shows minimal evidence for reduced spasticity with the use of intrathecal baclofen. Two further short-term studies showed reduction in spasticity with the use of intrathecal baclofen, but the authors used inappropriate methods of analysing the data, so it is uncertain whether these results are valid. All these studies had a small number of participants, making the findings less reliable. The research also provides evidence from one short term study and one longer term study (again, by the same investigators), that intrathecal baclofen therapy improves the comfort, ease of care and some aspects of quality of life for children with cerebral palsy. However, the results of the longer term study may have been influenced by both the participants and the investigators being aware of whether they were receiving treatment or allocated to the control group. This same study found that intrathecal baclofen improves gross motor function a little in children with cerebral palsy, but again, these results may have been influenced by the way the study was conducted. Further evidence of the effectiveness of intrathecal baclofen for treating spasticity is needed from other investigators in order to validate these results. There is little evidence from the short-term randomised controlled trials about the safety and economic implications of this treatment when long-term therapy is administered through an implanted device. For the same reasons, we could not reach a conclusion on whether the subsequent need for orthopaedic surgery is altered in children receiving intrathecal baclofen therapy.

10.1002/14651858.CD004552.pub2

cochrane-simplification-train-2393

cochrane-simplification-train-2393

Twenty-two trials which randomised approximately 6200 people to pioglitazone treatment were identified. Longest duration of therapy was 34.5 months. Published studies of at least 24 weeks pioglitazone treatment in people with type 2 diabetes mellitus did not provide convincing evidence that patient-oriented outcomes like mortality, morbidity, adverse effects, costs and health-related quality of life are positively influenced by this compound. Metabolic control measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint did not demonstrate clinically relevant differences to other oral antidiabetic drugs. Occurrence of oedema was significantly raised. The results of the single trial with relevant clinical endpoints (Prospective Pioglitazone Clinical Trial In Macrovascular Events - PROactive study) have to be regarded as hypothesis-generating and need confirmation. Until new evidence becomes available, the benefit-risk ratio of pioglitazone remains unclear. Different therapeutic indications for pioglitazone of the two big U.S. and European drug agencies should be clarified to reduce uncertainties amongst patients and physicians.

Twenty-two trials randomised approximately 6200 people to pioglitazone treatment. The longest duration of pioglitazone therapy was 34.5 months. Unfortunately, the published studies of at least 24 weeks pioglitazone treatment in people with type 2 diabetes mellitus did not provide convincing evidence that patient-oriented outcomes are positively influenced by this compound. The occurrence of oedema was significantly raised. The results of the single trial with relevant endpoints (Prospective Pioglitazone Clinical Trial In Macrovascular Events - PROactive study) have to be confirmed by other independent investigations. Until new evidence becomes available (several large trials are ongoing) the place of pioglitazone in the treatment of type 2 diabetes mellitus remains unclear. Furthermore, confusion arises due to different labelling of pioglitazone, for example in Europe and the USA. Consumers and physicians need clear guidance and transparent information about which studies exactly are used for the decisions of the relevant drug authorities.

10.1002/14651858.CD006060.pub2

cochrane-simplification-train-2394

cochrane-simplification-train-2394

Sixty-five RCTs (N=166,206) were included, evaluating four classes of anti-hypertensive drugs: ACE inhibitors (12 trials), beta-blockers (20), calcium channel blockers (18) and nitrates (18). Acute stroke was studied in 6 trials (all involving CCBs). Acute myocardial infarction was studied in 59 trials. In the latter setting immediate nitrate treatment (within 24 hours) reduced all-cause mortality during the first 2 days (RR 0.81, 95%CI [0.74,0.89], p<0.0001). No further benefit was observed with nitrate therapy beyond this point. ACE inhibitors did not reduce mortality at 2 days (RR 0.91,95%CI [0.82, 1.00]), but did after 10 days (RR 0.93, 95%CI [0.87,0.98] p=0.01). No other blood pressure lowering drug administered as an immediate treatment or short-term treatment produced a statistical significant mortality reduction at 2, 10 or ≥30 days. There was not enough data studying acute stroke, and there were no RCTs evaluating other acute cardiovascular events. Nitrates reduce mortality (4-8 deaths prevented per 1000) at 2 days when administered within 24 hours of symptom onset of an acute myocardial infarction. No mortality benefit was seen when treatment continued beyond 48 hours. Mortality benefit of immediate treatment with ACE inhibitors post MI at 2 days did not reach statistical significance but the effect was significant at 10 days (3-5 deaths prevented per 1000). There is good evidence for lack of a mortality benefit with immediate or short-term treatment with beta-blockers and calcium channel blockers for acute myocardial infarction.

This review looked at all studies where patients were randomized to one of these drugs or placebo, in this period. One class of blood pressure lowering drug, the so-called nitrates, demonstrated reduction in mortality in patients with heart attack. For 1000 patients treated 4 to 8 deaths were prevented during the first 2 days of this acute event. The ACE-inhibitors class also decrease mortality when continued for 10 days (3 to 5 deaths prevented per 1000). No other class of drug showed a reduction in mortality.

10.1002/14651858.CD006743.pub2

cochrane-simplification-train-2395

cochrane-simplification-train-2395

Information was available from 39 Cochrane reviews for 41 different analgesics or analgesic combinations (51 drug/dose/formulations) tested in single oral doses in participants with moderate or severe postoperative pain. This involved around 350 unique studies involving about 35,000 participants. Most studies involved younger participants with pain following removal of molar teeth. For most nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and combinations not containing opioids, there were few examples where participants experienced significantly more or fewer adverse events than with placebo. For aspirin 1000 mg and diflunisal 1000 mg, opioids, or fixed-dose combination drugs containing opioids, participants typically experienced significantly more adverse events than with placebo. Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events. Serious adverse events were rare, occurring a rate of about 1 in 3200 participants. Most reviews did not report specific adverse events. Despite ongoing problems with the measurement, recording, and reporting of adverse events in clinical trials and in systematic reviews, the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances, except at higher doses of some drugs, and in combinations including opioids.

In this overview, we used information from about 35,000 participants in about 350 studies to look specifically at the adverse events (unwanted effects) experienced with painkillers, and compared the results with those for placebo (dummy pill). Measuring adverse events is complicated because the particular method used to collect information influences how many adverse events are reported. Most people in the studies had wisdom teeth removed, were relatively young and fit, and were likely to take occasional painkillers. Adverse events may be different in people who are less well, older, or who take painkillers for several days or longer. The results we have showed that for most nonsteroidal anti-inflammatory drugs (painkillers like aspirin, ibuprofen, or diclofenac), paracetamol, and combinations of different painkillers that do not contain opioids (drugs like codeine), adverse events happened to the same proportion of people with painkillers and placebo. With aspirin 1000 mg, opioids, or fixed dose combinations containing opioids, people typically experienced significantly more adverse events than with placebo. A combination of ibuprofen and paracetamol resulted in significantly fewer adverse events than placebo. Serious adverse events were rare, occurring a rate of about 1 in 3200 people. The results are not unexpected for single dose studies, which are likely to be different from the situation when analgesics are taken over the medium or longer term.

10.1002/14651858.CD011407.pub2

cochrane-simplification-train-2396

cochrane-simplification-train-2396

Nineteen trials providing outcome data for 1597 young to middle-aged adults were included. Many trials were at high risk of bias reflecting inadequate methods of randomization, lack of blinding and incomplete assessment of outcome. Pooled data for primary outcomes, reported in a minority of trials, showed no statistically significant differences between the two graft choices for functional assessment (single leg hop test), return to activity, Tegner and Lysholm scores, and subjective measures of outcome. There were also no differences found between the two interventions for re-rupture or International Knee Documentation Committee scores. There were inadequate long-term results, such as to assess the development of osteoarthritis. All tests (instrumental, Lachman, pivot shift) for static stability consistently showed that PT reconstruction resulted in a more statically stable knee compared with HT reconstruction. Conversely, patients experienced more anterior knee problems, especially with kneeling, after PT reconstruction. PT reconstructions resulted in a statistically significant loss of extension range of motion and a trend towards loss of knee extension strength. HT reconstructions demonstrated a trend towards loss of flexion range of motion and a statistically significant loss of knee flexion strength. The clinical importance of the above range of motion losses is unclear. There is insufficient evidence to draw conclusions on differences between the two grafts for long-term functional outcome. While PT reconstructions are more likely to result in statically stable knees, they are also associated with more anterior knee problems.

This review included 19 studies reporting the outcomes of ACL reconstruction with patellar tendon versus hamstring tendon grafts in a total of 1597 young to middle-aged adults. Many trials used flawed methods that might have affected their results. The limited data available for functional outcomes including patient-rated assessment did not show whether one graft was better than the other. Similarly, there were no differences found between the two types of graft for re-rupture or in the results of an internationally used knee score. All tests for knee stability favoured patellar tendon grafts. Conversely, people had more anterior knee pain and discomfort with kneeling after patellar tendon reconstruction. After patellar tendon reconstruction, more people had some loss in their ability to straighten out their leg at the knee. In contrast, more people had some loss in their ability to bend their leg at the knee after hamstring tendon reconstruction. It is not clear how important these losses in range of motion of the knee were to the patients themselves. The review concluded that the current evidence was insufficient to recommend which of the two types of graft was better for ACL reconstruction.

10.1002/14651858.CD005960.pub2

cochrane-simplification-train-2397

cochrane-simplification-train-2397

Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette’s syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum. We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette’s syndrome.

The review authors summarised information from one clinical trial that compared botulinum toxin to a placebo, to treat tics in adults with Tourette’s syndrome. We found one small study. The study was limited by the number of participants (N = 18), who mainly had mild tics. We are very uncertain about the effects of botulinum toxin injections on reducing tic frequency and severity, and measures of overall well-being. Some participants experienced harms, which included weakness, restlessness, and neck discomfort following the injection. We do not know from the study whether participants who received the injection developed resistance to the botulinum injections, which would make them less effective over time. The evidence is current to 25 October 2017.

10.1002/14651858.CD012285.pub2

cochrane-simplification-train-2398

cochrane-simplification-train-2398

One new included study as well as further participants to a study already included was added to this update involving a further 39 participants. There were a total of three studies included involving 162 participants for this update. For this review two RCTs were included investigating secondary lymphoedema in 60 women after breast cancer surgery and 20 men and women after head and neck cancer surgery. One ongoing trial with preliminary results of 82 participants was also identified studying radiotherapy induced diarrhoea as a secondary outcome. All studies had considerable drawbacks with regards to quality and reporting. One study on secondary lymphoedema reported a decreased number of recurrent erysipela infections in the selenium supplementation group compared to placebo. The second study reported a decreased facial swelling in the selenium group in a two-week period following surgical tumour resection. However, results must be interpreted with caution and cannot be generalised to other populations. The ongoing trial on radiotherapy associated diarrhoea preliminarily reported a lower incidence of diarrhoea in participants receiving selenium supplementation concomitant to pelvic radiation, however, no data were presented. We must await publication of final results to discuss these findings in detail. No RCTs were found studying the effect of selenium supplementation on other therapy-associated toxicities or quality of life/performance status in cancer patients. There is insufficient evidence at present that selenium supplementation alleviates the side effects of tumour specific chemotherapy or radiotherapy treatments or that it improves the after-effects of surgery, or improves quality-of-life in cancer patients or reduces secondary lymphoedema. To date, research findings do not provide a basis for any recommendation in favour or against selenium supplementation in cancer patients. Potential hazards of supplementing a trace mineral should be kept in mind. Since the last version of this review, the one new additional study has not provided information to change the conclusions of the original review.

This systematic review looked at studies providing selenium supplements to cancer patients and found no clear evidence that selenium supplements improve side effects of cancer therapy. No adverse effects were reported in the studies, but evidence of overdosing, all be it unintentional and selenium intoxication has occurred in several selenium users. More research is needed to find out which doses of selenium supplements can be reasonably used by cancer patients and whether selenium supplements can affect the side effects of cancer therapy.

10.1002/14651858.CD005037.pub2

cochrane-simplification-train-2399

cochrane-simplification-train-2399

Seven studies including 494 participants formed the evidence base for this review. Drug treatments assessed in studies in the review included cholinergic agents, alpha-blockers, sedatives and prostaglandin on their own or in combinations. No statistically significant associations were reported between successful treatment or any other outcome and cholinergic agents, alpha-blockers and sedatives as monotherapies. A statistically significant association between intravesically administered prostaglandin and successful voiding was detected, Risk Ratio 3.07 (95% CI 1.22 to 7.72). A statistically significant association was detected between cholinergic agents combined with sedative and an improved likelihood of spontaneous voiding compared with placebo, Risk Ratio 1.39 (95% CI 1.07 to 1.82). Significant heterogeneity was identified between the two studies in this analysis, however. Whilst it may appear that cholinergic agents and intravesically administered prostaglandin offer most promise in the treatment of post-operative urinary retention, the evidence is weak. There is a need for further research into pharmacological alternatives to catheterisation in the treatment of this common surgical complication.

This review looked for studies that had considered the effectiveness of drugs used to help patients to empty their bladder after surgery. Few studies were found. There is some evidence that introducing an agent called prostaglandin into the bladder can help patients to regain the ability to empty their bladders. There is weaker evidence that drugs called cholinergics, combined with a sedative, can also help. There is a need for more research in this area.

10.1002/14651858.CD008023.pub2