GEM/cochrane-simplification huggingface dataset:
Abstract: 53 trials were included, most of which were cluster-randomised. The reporting quality of trials was poor, only 3.8% of them reporting adequate method of randomisation and program allocation concealment. Incomplete data was adequately addressed in 23% of the trials. Due to extensive heterogeneity across interventions, populations, and outcomes, the results were summarized only qualitatively. Six of the 11 trials evaluating alcohol-specific interventions showed some evidence of effectiveness compared to a standard curriculum. In 14 of the 39 trials evaluating generic interventions, the program interventions demonstrated significantly greater reductions in alcohol use either through a main or subgroup effect. Gender, baseline alcohol use, and ethnicity modified the effects of interventions. Results from the remaining 3 trials with interventions targeting cannabis, alcohol, and/or tobacco were inconsistent. This review identified studies that showed no effects of preventive interventions, as well as studies that demonstrated statistically significant effects. There was no easily discernible pattern in characteristics that would distinguish trials with positive results from those with no effects. Most commonly observed positive effects across programs were for drunkenness and binge drinking. Current evidence suggests that certain generic psychosocial and developmental prevention programs can be effective and could be considered as policy and practice options. These include the Life Skills Training Program, the Unplugged program, and the Good Behaviour Game. A stronger focus of future research on intervention program content and delivery context is warranted.

Plain-language summary: We conducted a Cochrane systematic review of 53 well-designed experimental studies that examined the effectiveness of school-based universal programs for the prevention of alcohol misuse in young people. The studies were divided into two major groups based on the nature of the prevention program: 1) programs targeting specifically prevention or reduction of alcohol misuse and 2) generic programs with wider focus for prevention (e.g., other drug use/abuse, antisocial behavior). In the review we found studies that showed no effects of the preventive program, as well as studies that demonstrated statistically significant effects. There was no easily discernible pattern in program characteristics that would distinguish studies with positive results from those with no effects. Most commonly observed positive effects across programs were for drunkenness and binge drinking. In conclusion, current evidence suggests that certain generic psychosocial and developmental prevention programs can be effective and could be considered as policy and practice options. These include the Life Skills Training Program, the Unplugged program, and the Good Behaviour Game.
Abstract: Sixteen trials met the inclusion criteria, involving 1643 children of whom 865 received a simple behavioural intervention. Within each comparison, outcomes were mostly addressed by single trials, precluding meta-analysis. The only exception was bladder training versus enuresis alarm therapy which included two studies and demonstrated that alarm therapy was superior to bladder training. In single small trials, rewards, lifting and waking and bladder training were each associated with significantly fewer wet nights, higher full response rates and lower relapse rates compared to controls. Simple behavioural interventions appeared to be less effective when compared with other known effective interventions (such as enuresis alarm therapy and drug therapies with imipramine and amitriptyline). However, the effect was not sustained at follow-up after completion of treatment for the drug therapies. Based on one small trial, cognitive therapy also appeared to be more effective than rewards. When one simple behavioural therapy was compared with another, there did not appear to be one therapy that was more effective than another. Simple behavioural methods may be superior to no active treatment but appear to be inferior to enuresis alarm therapy and some drug therapy (such as imipramine and amitriptyline). Simple behavioural therapies could be tried as first line treatment before considering enuresis alarm therapy or drug therapy, which may be more demanding and have adverse effects, although evidence supporting their efficacy is lacking.

Plain-language summary: The review found 16 trials which involved 1643 children. Most simple behavioural treatments were only studied in single small trials which makes the evidence less reliable. Simple treatments such as rewarding dry nights (e.g. with star charts), lifting and waking and bladder training appeared to be more effective than no treatment but they are not as effective when compared with other treatments known to work, such as enuresis alarm therapy and drug therapy. There does not appear to be one simple behavioural therapy that is more effective than another. On the other hand, simple treatments do not have any side effects or safety concerns. Therefore, simple methods could be tried as first line therapy before considering alarms or drugs for this common childhood condition.
Abstract: Nineteen studies (907 participants) met the inclusion criteria for this review. We included 13 studies (770 participants) in meta-analyses (417 traumatic brain injury, 304 stroke, 49 other acquired brain injury) reducing to 660 participants once non-included intervention groups were removed from three and four group studies. We were unable to obtain data from the remaining six studies. Three studies (134 participants) compared cognitive rehabilitation with sensorimotor therapy. None reported our primary outcome; data from one study was available relating to secondary outcomes including concept formation and ADL. Six studies (333 participants) compared cognitive rehabilitation with no treatment or placebo. None reported our primary outcome; data from four studies demonstrated no statistically significant effect of cognitive rehabilitation on secondary outcomes. Ten studies (448 participants) compared two different cognitive rehabilitation approaches. Two studies (82 participants) reported the primary outcome; no statistically significant effect was found. Data from eight studies demonstrated no statistically significant effect on the secondary outcomes. We explored the effect of restorative interventions (10 studies, 468 participants) and compensative interventions (four studies, 128 participants) and found no statistically significant effect compared with other interventions. We identified insufficient high-quality evidence to reach any generalised conclusions about the effect of cognitive rehabilitation on executive function, or other secondary outcome measures. Further high-quality research comparing cognitive rehabilitation with no intervention, placebo or sensorimotor interventions is recommended.

Plain-language summary: We found 19 relevant studies involving 907 people. We were able to combine the results of 13 of these studies including 660 participants (395 traumatic brain injury, 234 stroke, 31 other acquired brain injury). Only two of the studies (82 people) reported the outcome in which we were most interested (a general measure of executive function). We found no evidence that cognitive rehabilitation interventions were helpful for people with executive dysfunction for any other outcomes. We recommend that more research is carried out to determine whether cognitive rehabilitation can improve executive function after stroke and brain injury.
Abstract: Six studies met the inclusion criteria but were limited by small sample sizes, various treatment regimes used and outcomes assessed. The studies were overall of unclear quality. Data could only be pooled for the outcomes of treatment failure and hospitalisation. Other data could not be combined due to divergent outcome measurements. Meta-analysis revealed that children who received anticholinergics alone were significantly more likely to have treatment failure compared to those who received beta2-agonists from four trials on 171 children (odds ratio (OR) 2.27; 95% CI 1.08 to 4.75). Also, treatment failure on anticholinergics alone was more likely than when anticholinergics were combined with beta2-agonists from four trials on 173 children (OR 2.65; 95% CI 1.2 to 5.88). Data on clinical scores/symptoms that were measured on different scales were conflicting. Individual trials reported that lung function was superior in the combination group when compared with anticholinergic agents used alone. The use of anticholinergics was not found to be associated with significant side effects. In children over the age of two years with acute asthma exacerbations, inhaled anticholinergics as single agent bronchodilators were less efficacious than beta2-agonists. Inhaled anticholinergics were also less efficacious than inhaled anticholinergics combined with beta2-agonists. Inhaled anticholinergic drugs alone are not appropriate for use as a single agent in children with acute asthma exacerbations.

Plain-language summary: We found six small trials of unclear quality answering these two questions. We found data from four trials on 171 children comparing anticholinergics with beta2-agonists. Children on anticholinergics alone were significantly more likely to experience treatment failure than those on beta2-agonists (odds ratio (OR) 2.27; 95% CI 1.08 to 4.75). We also found data from four trials on 173 children comparing children on anticholinergics alone with children on anticholinergics plus beta2-agonists. In this case, treatment failure was more likely in children taking anticholinergics only than if they were combined with beta2-agonists (OR 2.65; 95% CI 1.2 to 5.88). We were only able to combine data for treatment failure and hospitalisation. In summary, we found that inhaled anticholinergics used on their own are less effective than inhaled beta2-agonists used alone or in combination with anticholinergics. Inhaled anticholinergics seem safe, with no significant side effects apparent.
Abstract: One trial, which included 112 infants, met the inclusion criteria for this review. Term newborn infants on mechanical ventilation with the need for continuous analgesia and sedation with fentanyl and midazolam were eligible for enrollment during the first 96 hours of ventilation. Study authors administered clonidine 1 μg/kg/h or placebo on day 4 after intubation. We found no differences between the two groups in all-cause death during hospitalization (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.12 to 3.98). The quality of the evidence supporting these findings is low owing to imprecision of the estimates (one study; few events). The median (interquartile range) duration of mechanical ventilation was 7.1 days (5.7 to 9.1 days) in the clonidine group and 5.8 days (4.9 to 7.9 days) in the placebo group, respectively (P = 0.070). Among secondary outcomes, we found no differences in terms of duration of stay in the intensive care unit. Sedation scale values (COMFORT) and analgesia scores (Hartwig) during the first 72 hours of infusion of study medication were lower in the clonidine group than in the placebo group. At present, evidence is insufficient to show the efficacy and safety of clonidine for sedation and analgesia in term and preterm newborn infants receiving mechanical ventilation.

Plain-language summary: In medical literature searches completed to January 2017, we identified and included one trial with 112 newborns comparing clonidine with placebo. We did not identify funding by industry for the included trial. Clonidine did not reduce death, duration of mechanical ventilation, or duration of stay in the intensive care unit. Sedation and pain scale values were lower among newborns receiving clonidine. Owing to the small number of newborns included in the single included trial, we are uncertain as to whether clonidine is effective or safe in providing analgesia and sedation for mechanically ventilated neonates.
Abstract: 20 parallel-group trials were included. The reporting quality of trials was poor, only 25% and 5% of them reporting adequate method of randomisation and program allocation concealment, respectively. Incomplete data was adequately addressed in about half of the trials and this information was unclear for about 20% of the trials. Due to extensive heterogeneity across interventions, populations, and outcomes, the results were summarized only qualitatively. 12 of the 20 trials showed some evidence of effectiveness compared to a control or other intervention group, with persistence of effects ranging from 3 months to 3 years. Of the remaining 8 trials, one trial reported significant effects using one-tailed tests and 7 trials reported no significant effects of the multi-component interventions for reducing alcohol misuse. Assessment of the additional benefit of multiple versus single component interventions was possible in 7 trials with multiple arms. Only one of the 7 trials clearly showed a benefit of components delivered in more than one setting. There is some evidence that multi-component interventions for alcohol misuse prevention in young people can be effective. However, there is little evidence that interventions with multiple components are more effective than interventions with single components.

Plain-language summary: We conducted a Cochrane systematic review of 20 randomised controlled trials that examined the effectiveness of universal multi-component programs for the prevention of alcohol misuse in young people. Multi-component prevention programs are defined as those prevention efforts that deliver interventions in multiple settings, for example in both school and family settings, typically combining school curricula with a parenting intervention. A majority of the studies included in this review reported positive effects of multi-component programs for the prevention of alcohol misuse in young people, with effects persisting into the medium- and longer-term. But a notable proportion of trials reported no statistically significant effects. In seven studies we were able to assess the impact of single versus multiple components, and only 1 out of the 7 studies clearly showed a benefit of components delivered in more than one setting. In conclusion, there is some evidence that multi-component interventions for alcohol misuse prevention in young people can be effective. However, there is little evidence that interventions with multiple components are more effective than interventions with single components.
Abstract: Fifty-one published and unpublished trials (representing 55 group comparisons, 10,797 participants) met the inclusion criteria. In asthmatics with mild to moderate disease who were not on oral steroids, FP did not exhibit a dose-response effect in the lower dose comparisons in FEV1 (50mcg, 100mcg, 200mcg and 4-500mcg daily). There were no statistically significant differences between 4-500mcg and 800-1000mcg, and between 50-100 and 800-1000mcg of FP. When 200mcg was compared with 800-1000mcg daily FEV1 favoured the four/five fold increase. For PEF, a dose response was present with FP when low and moderate, and low and high doses of FP were compared. There was no evidence of a dose-response effect on symptoms or rescue beta-2 agonist use. The likelihood of hoarseness and oral candidiasis was significantly greater for the higher doses (800 to 1000 µg/day). People with oral steroid-dependent asthma treated with FP (2000 µg/day) were significantly more likely to reduce oral prednisolone than those on 1000 to 1500 µg/day (Peto odds Ratio 2.8, 95% CI 1.3 to 6.3). The highest dose also allowed a significant reduction in daily oral prednisolone dose compared to 1000 to 1500 µg/day (WMD 2.0 mg/day, 95% CI 0.1 to 4.0 mg/day). We have not found evidence of a pronounced dose response in FEV1 with increasing doses of fluticasone. The number of studies contributing to our primary outcomes was low. At dose ratios of 1:2, there are statistically significant differences in favour of the higher dose in morning peak flow across the low dose range. The clinical impact of these differences is open to interpretation. Patients with moderate disease achieve similar levels of asthma control on medium doses of fluticasone (400 to 500 µg/day) as they do on high doses (800 to 1000 µg/day). More work in severe asthma would help to confirm that doses of FP above 500 µg/day confer greater benefit in this subgroup than doses of around 200 µg/day. In oral corticosteroid-dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 µg/day.

Plain-language summary: This review examined the effectiveness of FP when given at different doses for treating asthma in children and adults. High doses (800 to 1000 microgram per day) led to small improvements in measures of airway opening compared to low doses (50 to 100 microgram per day) in people with mild to moderate asthma. High dose FP did not lead to clear improvements in symptoms over the lower dose and increased the risk of a hoarse voice and fungal mouth infections. In people with severe asthma, very high doses FP (2000 microgram per day) appeared to allow more people on oral steroids to stop or reduce their dose of oral steroid tablets compared to lower doses of FP (1000 to 1500 microgram per day).
Abstract: We included 21 trials (19 adult, two paediatric) totaling 1676 participants (1628 adults, 48 children) in this updated review. Pooled data from 16 eligible trials reporting weaning duration indicated that automated closed loop systems reduced the geometric mean duration of weaning by 30% (95% confidence interval (CI) 13% to 45%), however heterogeneity was substantial (I2 = 87%, P < 0.00001). Reduced weaning duration was found with mixed or medical ICU populations (42%, 95% CI 10% to 63%) and Smartcare/PS™ (28%, 95% CI 7% to 49%) but not in surgical populations or using other systems. Automated closed loop systems reduced the duration of ventilation (10%, 95% CI 3% to 16%) and ICU LOS (8%, 95% CI 0% to 15%). There was no strong evidence of an effect on mortality rates, hospital LOS, reintubation rates, self-extubation and use of non-invasive ventilation following extubation. Prolonged mechanical ventilation > 21 days and tracheostomy were reduced in favour of automated systems (relative risk (RR) 0.51, 95% CI 0.27 to 0.95 and RR 0.67, 95% CI 0.50 to 0.90 respectively). Overall the quality of the evidence was high with the majority of trials rated as low risk. Automated closed loop systems may result in reduced duration of weaning, ventilation and ICU stay. Reductions are more likely to occur in mixed or medical ICU populations. Due to the lack of, or limited, evidence on automated systems other than Smartcare/PS™ and Adaptive Support Ventilation no conclusions can be drawn regarding their influence on these outcomes. Due to substantial heterogeneity in trials there is a need for an adequately powered, high quality, multi-centre randomized controlled trial in adults that excludes 'simple to wean' patients. There is a pressing need for further technological development and research in the paediatric population.

Plain-language summary: We identified 21 studies that provided information on a total of 1676 people including 1628 adults and 48 children. The evidence was current to 30th September 2013. Studies were conducted in people with medical reasons such as pneumonia and other infections for needing admission to ICU, people admitted following trauma, and people admitted after heart or other forms of surgery. As well, various commercially available computerized weaning systems were studied. We found that computerized weaning systems resulted in a reduced weaning duration as well as reduced overall time on the ventilator and stay in an ICU. The average time required for a person to be weaned off the ventilator was reduced by 30%. The overall time on the ventilator was reduced by 10% and the length of stay in ICU by 8%. Not all studies demonstrated these reductions. Studies conducted only in people admitted to ICU following surgery did not demonstrate reductions in weaning, overall time on a ventilator or ICU stay. Because of differences in the methods and results of some studies included in this review, further large scale research is warranted. There is also a need for more studies that examine the effect of computerized weaning systems in children.
Abstract: Thirteen studies on 1505 infants were included. Infants given opioids showed reduced premature infant pain profile (PIPP) scores compared to the control group (weighted mean difference -1.71; 95% confidence interval -3.18 to -0.24). Differences in execution and reporting of trials mean that this meta-analysis should be interpreted with caution. Heterogeneity was significantly high in all analyses of pain, even when lower quality studies were excluded and analysis limited to very preterm newborns. Meta-analyses of mortality, duration of mechanical ventilation, and long and short-term neurodevelopmental outcomes showed no statistically significant differences. Very preterm infants given morphine took significantly longer to reach full enteral feeding than those in control groups (weighted mean difference 2.10 days; 95% confidence interval 0.35 to 3.85). One study compared morphine with a sedative: the treatments showed similar pain scores, but morphine had fewer adverse effects. There is insufficient evidence to recommend routine use of opioids in mechanically ventilated newborns. Opioids should be used selectively, when indicated by clinical judgment and evaluation of pain indicators. If sedation is required, morphine is safer than midazolam. Further research is needed.

Plain-language summary: This review found no evidence for routine use of opioids for newborns on breathing machines. Although relief of pain was variable, opioids were no better or worse for babies (in terms of death, strokes, future development, duration of ventilation or hospital stay) than other drugs or placebo. Further research is needed.