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

Plain-language summary: The review of studies including 15 trials and 1422 children found that there were some encouraging results in short term studies when nedocromil was compared on its own with placebo, particularly with regard to lung function tests. However, these results were not confirmed in one large, longer term study of four to six years duration, which did not show significant difference in the primary outcome of symptom free days. This study was conducted in children who had mild asthma. There may be a role for nedocromil in the management of moderate asthma, but it should be assessed in relation to inhaled steroids, whose efficacy is well-established. This particularly important in symptomatic asthma.
Abstract: Two studies (enrolling 118 participants) examined the association between intense hydration and ureteric colic outcomes. There was no significant difference in pain at six hours (1 study, 60 participants: RR 1.06, 95% CI 0.71 to 1.57), surgical stone removal (1 study, 60 participants: RR 1.20, 95% CI 0.41 to 3.51) or manipulation by cystoscopy (1 study, 60 participants: RR 0.67, 95% CI 0.21 to 2.13) when no fluids over six hours was compared to three litres IV fluids administered over a six hour period. There was no difference in stone clearance (1 study 43 participants: RR 1.38, 95% CI 0.50 to 3.84), hourly pain score or patients' narcotic requirements (P > 0.05 for all comparisons) when forced IV hydration of two litres over four hours was compared with minimal IV hydration at 20 mL/hour. One study did not provide any details which would have allowed us to assess any of the risk of bias items (selection, detection, performance, attrition or reporting bias). The second study did not report the method of randomisation or allocation (selection bias - unclear), they reported that the patients were blinded to therapy (low risk of bias), analgesics were administered according to predetermined pain score criteria (low risk), and assessment of stone passage was unlikely to have been biased by knowledge of group assignment (low risk). However the second study also reported a high percentage of participants excluded post randomisation (26%; high risk of bias). We were unable to assess or ascertain any of the other risk of bias items. We found no reliable evidence in the literature to support the use of diuretics and high volume fluid therapy for people with acute ureteric colic. However, given the potential positive therapeutic impact of fluids and diuretics to facilitate stone passage, the capacity of these interventions warrants further investigation to determine safety and efficacy profiles.

Plain-language summary: This review aimed to determine if increased fluids and diuretics or both could hasten the passage of stones and improve symptoms. Neither our initial review nor this subsequent update identified sufficient evidence to enable conclusions to be determined about the safety and effectiveness of increasing fluids or diuretics or both to treat people with acute ureteric colic. More and larger randomised controlled studies are required.
Abstract: Two ITS studies, conducted between 1972 and 1984, met our inclusion criteria for the primary objective, and one study contributed to the quantitative analysis. This study was conducted in India, reported the incidence of malaria in four separate sites, and covered a total population of 18,460 people. In the pooled analysis across sites, there was no step effect for the incidence of uncomplicated malaria (step rate ratio 1.00, 95% confidence interval (CI) 0.51 to 1.92). There was an effect on the slope: the number of cases was reduced by 15% per month (slope rate ratio 0.85, 95% CI 0.79 to 0.91). Using these ratios, we estimated the effect of 12 months of space spraying on malaria incidence to be a reduction from 6 cases to 1 case per month per 1000 population (95% CI 0 to 2 cases, very low-certainty evidence). The second study reported the impact of space spraying on malaria incidence and adult mosquito density in a population of 15,106 in Haiti, but it did not provide data from previous years. Thus, we could not estimate an effect of space spraying that was independent from temporal trends. For the review's secondary objective, we identified a further two studies in addition to the two ITS studies; both used a CBA design and were conducted between 1973 and 2000. The four studies used a range of delivery methods including handheld, vehicle-mounted, and aircraft-mounted spraying equipment. A variety of insecticides, doses, and spraying times were also used, with methods typically determined based on environmental factors and vector profiles. Evidence from one state in India conducted over 30 years ago suggests an effect of space spraying on the incidence of malaria, but the certainty of the evidence is very low. Reliable research in a variety of settings will help establish whether and when this intervention may be worthwhile.

Plain-language summary: After searching for relevant trials up to 18 April 2018, we identified four studies conducted between 1972 and 2000. Across the four studies, a range of insecticide delivery methods were used, including handheld, vehicle-mounted, and aircraft-mounted spraying equipment. A variety of different insecticides, doses, and spraying times were also used to suit the local environment and the behaviour of the targeted mosquito species. In three studies, the evidence was considered to be unsuitable for reliably assessing the impact of space spraying on the number of cases of malaria. The remaining study, which took place in a single state in India and covered a combined population of 18,460 people, reported the number of malaria cases in the years preceding and following the introduction of space spraying. The evidence suggested that space spraying led to a decrease in the number of cases of malaria, but as the trial was conducted over 30 years ago and within one state in India, we cannot be certain that these findings are applicable in other areas where malaria occurs. Reliable research in a variety of settings will help to establish whether and when this intervention may be worthwhile.
Abstract: 165 trials were reviewed and eight were included; a total of 461 patients have been studied (229 with CBA; 232 with intermittent beta-agonists). Overall, admission to hospital was reduced with CBA compared to intermittent beta-agonists (RR: 0.68; 95% CI: 0.5 to 0.9); patients with severe airway obstruction at presentation appeared to benefit most from this intervention (RR: 0.64; 95% CI: 0.5 to 0.9). Patients receiving CBA demonstrated small but statistically significant improvements in pulmonary function tests when all studies were pooled. Patients receiving CBA had greater improvements in % predicted FEV-1 (SMD: 0.3; 95% CI: 0.03 to 0.5) and PEFR (SMD: 0.33; 95% CI: 0.1 to 0.5); this effect was observed by 2-3 hours. Continuous treatment was generally well tolerated, with no clinically important differences observed in pulse rate (WMD: -2.87; 95% CI: -6.0 to 0.3) or blood pressure (WMD: -1.75; 95% CI: -5.6 to 2.1) between the treatment groups. Tremor was equally common in both groups (OR: 0.81; 95% CI: 0.5 to 1.3) and potassium concentration was unchanged (WMD: 0.02; 95% CI: -0.2 to 0.2). Current evidence supports the use of CBA in patients with severe acute asthma who present to the emergency department to increase their pulmonary functions and reduce hospitalisation. Moreover, CBA treatment appears to be safe and well tolerated in patients who receive it.

Plain-language summary: This review has collected information from randomised controlled trials comparing continuous to intermittent nebulised delivery methods in acute asthma attacks. Overall, differences were found between the two methods, with continuous nebulisers producing a modest reduction in admissions compared to intermittent beta-agonist therapy. This finding was especially pronounced in severe acute asthma. Continuous nebuliser therapy may be more effective than intermittent nebulisers for delivering beta-agonist drugs to relieve airway spasm in selected asthma populations.
Abstract: We identified 83 publications and 29 were included, representing 15 data sets (475 participants). There was insufficient evidence to confirm or exclude any differences, between CCPT and other airway clearance techniques in terms of respiratory function measured by standard lung function tests. Studies undertaken during acute exacerbations demonstrated relatively large gains in respiratory function irrespective of airway clearance technique. Longer-term studies demonstrated smaller improvements or deterioration over time. Ten studies reported individual preferences for technique, with participants tending to favour self-administered techniques. Heterogeneity in the measurement of preference precluded these data from meta-analysis. This review was unable to demonstrate any advantage of CCPT over other airway clearance techniques in terms of respiratory function, but this may have reflected insufficient evidence rather than real equivalence between methods. There was a trend for participants to prefer self-administered airway clearance techniques. Limitations of this review included a paucity of well-designed, adequately-powered, long-term trials.

Plain-language summary: We looked for studies lasting over one week. We included fifteen studies in the review. These studies did not show any difference between chest physiotherapy and other therapies in terms of lung function. Studies of acute infections showed improved lung function irrespective of type of treatment. Longer-term studies showed smaller improvements or decline. In ten studies participants preferred techniques they administered on themselves. The review was limited by the lack of well-designed long-term trials. We did not find evidence that conventional chest physiotherapy techniques were any better than other treatments for lung function. We can not recommend any single treatment over another at this time.
Abstract: Four studies met all of the inclusion criteria (with a total of 40 participants). Three subclasses of anxiety medications were used including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and azapirones. Although two studies used SSRIs as the intervention (total of 21 participants), we were unable to meta-analyse the anxiety outcomes as one study had a standard deviation of zero for the control group. Included studies had relatively poor quality including small sample sizes and short follow-up periods. Due to the small number of included studies, we were unable to meta-analyse all the subclasses of medications. Due to the sub-optimal quality of the trials and statistically non-significant results, it is not possible to draw any conclusions for treatment. This review highlights the paucity of data in this area. As such, there is a need for scientifically rigorous research trials to evaluate the role of pharmacological interventions for anxiety disorders in patients with COPD, using a sample size large enough to demonstrate meaningful clinical significance.

Plain-language summary: This systematic review of four studies (total of 40 participants) found insufficient evidence of benefit for any of the three classes of medications included in this review. There is a considerable lack of evidence to address pharmacological interventions for anxiety disorders in patients with COPD. We recommend that new research be conducted to ascertain the best mode of treatment for anxiety within this population. This new research needs to be of good methodological design, investigate an adequate number of patients and have a meaningful length of follow-up.
Abstract: We identified three randomised controlled trials (RCTs) of rhIGF-I, involving 779 participants, for inclusion in the analysis. In a European trial (183 participants) the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08). In a North American trial (266 participants), the MD after nine months was -6.00 (95% CI -10.99 to -1.01). The combined analysis from both RCTs showed a MD after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. There was an increased risk of injection site reactions with rhIGF-I (risk ratio 1.26, 95% CI 1.04 to 1.54). . A second North American trial (330 participants) used a novel primary end point involving manual muscle strength testing. No differences were demonstrated between the treated and placebo groups in this study. All three trials were at high risk of bias. Meta-analysis revealed a significant difference in favour of rhIGF-I treatment; however, the quality of the evidence from the two included trials was low. A third study showed no difference between treatment and placebo. There is no evidence for increase in survival with IGF1. All three included trials were at high risk of bias.

Plain-language summary: Three randomised controlled trials (RCTs) involving 779 participants measured disease progression on special clinical rating scales of disease severity in ALS. The review authors collected data about adverse events from the included trials. The combined results from the two included studies that used the rating scale (AALSRS) showed a small significant benefit in favour of rhIGF-I. Significant flaws in the trial designs make the statistically significant benefits in some outcomes of questionable relevance. There was an increased risk of injection site reactions with rhIGF-I. A third study using a different outcome measure showed no difference between treatment and placebo. Taken together, the available RCTs do not provide information supporting the hypothesis that rhIGF-I is an effective disease modifying treatment for ALS. All three included studies showed a high risk of bias. These issues very seriously detracted from the ability of this review to fulfil its objectives.
Abstract: Eighteen trials were included, involving a total of 10,049 participants. Trials differed considerably in their inclusion criteria, outcomes measured, and type of lipid-lowering therapy used. Only one trial (PQRST) reported a detrimental effect of active treatment on blood lipid/lipoprotein levels. The pooled results from all eligible trials indicated that lipid-lowering therapy had no statistically significant effect on overall mortality (Odds Ratio (OR) 0.86; 95% Confidence Interval (CI) 0.49 to 1.50) or on total cardiovascular events (OR 0.8; 95% CI 0.59 to 1.09). However, subgroup analysis which excluded PQRST showed that lipid-lowering therapy significantly reduced the risk of total cardiovascular events (OR 0.74; CI 0.55 to 0.98). This was primarily due to a positive effect on total coronary events (OR 0.76; 95% CI 0.67 to 0.87). Greatest evidence of effectiveness came from the use of simvastatin in people with a blood cholesterol ≥ 3.5 mmol/litre (HPS). Pooling of the results from several small trials on a range of different lipid-lowering agents indicated an improvement in total walking distance (Mean Difference (MD) 152 m; 95% CI 32.11 to 271.88) and pain-free walking distance (WMD 89.76 m; 95% CI 30.05 to 149.47) but no significant impact on ankle brachial index (WMD 0.04; 95% CI -0.01 to 0.09). Lipid-lowering therapy is effective in reducing cardiovascular mortality and morbidity in people with PAD. It may also improve local symptoms. Until further evidence on the relative effectiveness of different lipid-lowering agents is available, use of a statin in people with PAD and a blood cholesterol level ≥ 3.5 mmol/litre is most indicated.

Plain-language summary: Eighteen randomised controlled trials were included in the review, involving a total of 10,049 participants (78% were men) from seven different countries. The trials compared lipid-lowering therapy with placebo or usual treatment for at least 90 days. They differed considerably in the inclusion criteria, outcomes measured, and type of lipid-lowering therapy used. Lipid-lowering therapies improved walking distance. The effect of lipid-lowering therapy on death from any cause in people with peripheral artery disease was inconclusive. Using drugs to lower blood lipids had a beneficial effect on the incidence of total cardiovascular events, due primarily to an overall reduction in coronary events (OR 0.8; 95% Confidence Interval 0.7 to 0.9). The only type of drug for which consistent, clear evidence of a beneficial effect on total cardiovascular events, total coronary events and stroke was available, was the statins. The greatest evidence was with simvastatin in people with a blood cholesterol level of at least 3.5 mmol/litre. The evidence on side effects was inconclusive in these trials.
Abstract: A total of 2306 references were found from our searches, 61 of which were identified as potential trials comparing surgery and sclerotherapy. However, only nine randomised trials, described in a total of 14 separate papers, fulfilled the inclusion criteria. Fifty trials were excluded and one trial is ongoing and is due for completion in 2004. The trials used a variety of outcome measures and classification systems which made direct comparison between trials difficult. However, the trend was for sclerotherapy to be evaluated as significantly better than surgery at one year; after one year (sclerotherapy resulted in worse outcomes) the benefits with sclerotherapy were less, and by three to five years surgery had better outcomes. The data on cost-effectiveness was not adequately reported. There was insufficient evidence to preferentially recommend the use of sclerotherapy or surgery. There needs to be more research that specifically examines both costs and outcomes for surgery and sclerotherapy.

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

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