GEM/cochrane-simplification huggingface dataset:
Abstract: Twenty RCTs met the inclusion criteria. Concomitant therapy varied from none to any other bronchodilator plus corticosteroid (oral and inhaled). The following outcomes were significantly different when compared to placebo. Forced expiratory volume in one second (FEV1) improved with treatment: Weighted Mean Difference (WMD) 100 ml; 95% Confidence Interval (CI) 40 to 160 ml. Similarly for forced vital capacity (FVC): WMD 210 ml 95%CI 100 to 320. Two studies reported an improvement in maximum oxygen consumption (VO2 max); WMD 195 ml/min, 95%CI 113 to 278. At rest, arterial oxygen tension at rest (PaO2) and arterial carbon dioxide tension at rest (PaCO2) both improved with treatment (WMD 3.2 mm Hg; 95%CI 1.2 to 5.1, and WMD -2.4 mm Hg; 95%CI -3.5 to -1.2, respectively). Walking distance tests did not improve (four studies, Standardised Mean Difference 0.30, 95%CI -0.01 to 0.62), neither did Visual Analogue Score for breathlessness in two small studies (WMD 3.6, 95%CI -4.6 to 11.8). The Relative Risk (RR) of nausea was greater with theophylline (RR 7.7; 95%CI 1.5 to 39.9). However, patients' preference for theophylline was greater than that for placebo (RR 2.27; 95%CI 1.26 to 4.11). Very few participants withdrew from these studies for any reason. Theophylline has a modest effect on FEV1 and FVC and slightly improves arterial blood gas tensions in moderate to severe COPD. These benefits were seen in participants receiving a variety of different concomitant therapies. Improvement in exercise performance depended on the method of testing. There was a very low dropout rate in the studies that could be included in this review, which suggests that recruited participants may have been known by the investigators to be theophylline tolerant . This may limit the generalisability of these studies.

Plain-language summary: This systematic review shows that orally administered theophylline improves lung function and levels of oxygen and carbon dioxide in the blood. However, there is limited data on its effect on symptoms, exercise capacity or quality of life. Despite being associated with increased side effects, particularly nausea, participants preferred theophylline over placebo.
Abstract: We included one RCT that compared nebulised recombinant human deoxyribonuclease (rhDNase) with placebo in 40 children with airway malacia and a respiratory tract infection. We assessed it to be a RCT with overall low risk of bias. Data analysed in this review showed that there was no significant difference between groups for the primary outcome of proportion cough-free at two weeks (odds ratio (OR) 1.38; 95% confidence interval (CI) 0.37 to 5.14). However, the mean change in night time cough diary scores significantly favoured the placebo group (mean difference (MD) 1.00; 95% CI 0.17 to 1.83, P = 0.02). The mean change in daytime cough diary scores from baseline was also better in the placebo group compared to those on nebulised rhDNase, but the difference between groups was not statistically significant (MD 0.70; 95% CI -0.19 to 1.59). Other outcomes (dyspnoea, and difficulty in expectorating sputum scores, and lung function tests at two weeks also favoured placebo over nebulised rhDNase but did not reach levels of significance. There is currently an absence of evidence to support any of the therapies currently utilised for management of intrinsic tracheomalacia. It remains inconclusive whether the use of nebulised rhDNase in children with airway malacia and a respiratory tract infection worsens recovery. It is unlikely that any RCT on surgically based management will ever be available for children with severe life-threatening illness associated with tracheomalacia. For those with less severe disease, RCTs on interventions such as antibiotics and chest physiotherapy are clearly needed. Outcomes of these RCTs should include measurements of the trachea and physiological outcomes in addition to clinical outcomes.

Plain-language summary: We wanted to find out which out of these possible treatments was most effective. We found only one randomised controlled trial (RCT) that assessed nebulised recombinant human deoxyribonuclease (rhDNase) which helps in breaking down the mucous and has been shown to be useful in aiding airway clearance in cystic fibrosis compared to placebo (no active treatment) in children with both tracheomalacia and a concurrent respiratory infection. This trial showed no evidence of benefit in terms of the number of children who were cough-free two weeks after treatment. Also, there was less coughing reported, both during the day and at night, in the group who did not receive the intervention - however these differences were not statistically significant. With the lack of evidence, the routine use of any therapies for intrinsic tracheomalacia cannot be recommended given the cost of nebulised rhDNase and the likely harmful effect. The decision to subject a child to any surgical or medical based therapies will have to be made on an individual basis, with careful consideration of the risk-benefit ratio for each individual situation. It is unlikely that any RCT on surgically based management will ever be available for children with severe life-threatening illness associated with tracheomalacia. For those with less severe disease, RCTs on interventions such as antibiotics and chest physiotherapy are needed.
Abstract: We included 36 trials involving 6914 people. There was variation in the antibiotics used, patient characteristics and risk of RTIs and mortality in the control groups. In trials comparing a combination of topical and systemic antibiotics, there was a significant reduction in both RTIs (number of studies = 16, odds ratio (OR) 0.28, 95% confidence interval (CI) 0.20 to 0.38) and total mortality (number of studies = 17, OR 0.75, 95% CI 0.65 to 0.87) in the treated group. In trials comparing topical antimicrobials alone (or comparing topical plus systemic versus systemic alone) there was a significant reduction in RTIs (number of studies = 17, OR 0.44, 95% CI 0.31 to 0.63) but not in total mortality (number of studies = 19, OR 0.97, 95% CI 0.82 to 1.16) in the treated group. A combination of topical and systemic prophylactic antibiotics reduces RTIs and overall mortality in adult patients receiving intensive care. Treatment based on the use of topical prophylaxis alone reduces respiratory infections but not mortality. The risk of resistance occurring as a negative consequence of antibiotic use was appropriately explored only in one trial which did not show any such effect.

Plain-language summary: This review includes 36 studies involving 6914 patients treated in ICUs to investigate whether the administration of antibiotics prevents the development of infections. Antibiotics were administered in two different ways. In some studies antibiotics were applied both directly to the oropharynx via a nasogastric tube (topical) and intravenously (systemic). In other studies they were applied only topically. Our results show that when patients received the combination of topical plus systemic antibiotics there were less infections and deaths. When patients received only topical treatment there were less infections but the number of deaths was not changed. Although this treatment seems to work it is not widely used in clinical practice because there is concern about the possible development of antibiotic resistance (that is, bacteria become unresponsive to drugs).
Abstract: Five cluster-randomised controlled studies met the inclusion criteria. All of them investigated educational approaches. Two studies offered consultation in addition and two other studies offered guidance for nursing staff in addition. Four studies examined nursing home residents and one study residents in group dwelling units. No studies in community settings were included. Three studies included only one or two nursing homes per study condition. Overall, methodological quality of studies was low. The studies revealed inconsistent results. One study in the nursing home setting documented an increase of PR use in both groups after eight months, while the other three studies found reduced use of PR in the intervention groups after seven and 12 months of follow up respectively. The single study examining residents in group dwelling units found no change in PR use in the intervention group after six months whereas PR use increased significantly in the control group. There is insufficient evidence supporting the effectiveness of educational interventions targeting nursing staff for preventing or reducing the use of physical restraints in geriatric long-term care.

Plain-language summary: We reviewed whether interventions aimed at preventing and reducing the use of PR in geriatric long-term care settings are effective. We identified five small-sized randomised controlled studies suitable for inclusion. All studies examined educational interventions targeted at nursing staff. Four studies investigated residents in nursing homes and one in group dwelling units. The methodological quality of all studies was limited. Results of the studies were inconsistent. One study with higher methodological quality showed no reduction in PR use. Three other studies with lower methodological quality found their intervention to be effective. Thus, current evidence on interventions for the reduction or prevention of PR use in long-term geriatric care does not support a clear conclusion. Ongoing and unpublished research might alter the results of the review.
Abstract: The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects. In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.

Plain-language summary: We found six trials with 1758 participants. Of these, five studies looked at on-demand deprescribing and one trial looked at abruptly stopping PPIs. Participants were aged 48 to 57 years, except for one trial (average age of 73 years). The majority of participants had moderate heart burn and acid reflux with milder forms of esophagitis (inflammation of the food pipe that may lead to damage). We found that deprescribing methods led to worse symptoms control while considerably reducing pill use. Deprescribing PPIs may lead to side effects such as inflammation of the esophagus. Very few data were available to make a conclusion regarding long-term benefits and harms of PPI reduction or discontinuation. Overall, the quality of evidence for this review ranged from very low to moderate. Trials were inconsistent with how they reported symptom control. There were also limitations in how the studies were conducted (e.g. participants and investigators may have known which medicine they received), which lowered the quality of evidence. Other contributing factors included small sample sizes for most trials and inconsistent results between studies.
Abstract: The search identified five studies on oral immunoglobulin for the prevention of NEC of which three met the inclusion criteria. In this review of the three eligible trials (including 2095 neonates), the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC (typical risk ratio (RR) 0.84, 95% confidence interval (CI) 0.57 to 1.25; typical risk difference (RD) -0.01, 95% CI -0.03 to 0.01; 3 studies, 1840 infants), suspected NEC (RR 0.84, 95% CI 0.49 to 1.46; RD -0.01, 95% CI -0.02 to 0.01; 1 study, 1529 infants), need for surgery (typical RR 0.21, 95% CI 0.02 to 1.75; typical RD -0.03, 95% CI -0.06 to 0.00; 2 studies, 311 infants) or death from NEC (typical RR 1.10, 95% CI 0.47 to 2.59; typical RD 0.00, 95% CI -0.01 to 0.01; 3 studies, 1840 infants). Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomized controlled trials of oral IgA alone for the prevention of NEC.

Plain-language summary: We searched the medical literature through January 2016 and found three randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) (with 2095 newborn infants). Treatment was started either in the first 24 hours following birth (two small studies) or following commencement of oral feeding (enteral) (one large well-controlled study). In this large study, infants generally received breast milk, whereas they received formula milk in the other two studies. Giving immunoglobulin (IgG alone or IgG plus IgA combination) did not reduce the incidence of NEC, need for surgery related to NEC or death from NEC, either during or after the study period. Immunoglobulins could possibly cause breakdown of red blood cells (called haemolysis) (red blood cells are common cells in the blood that delivery oxygen to organs), but no clinically important haemolysis was apparent. There were no other reported side effects. There was low-very low evidence for all the major outcomes. The major factor that affected the quality of evidence was the lack of precision in the result estimates, as the calculated plausible range of the effects (the 95% confidence intervals) were wide.
Abstract: Twenty-three trials involving 2467 people were included. Comparing methadone versus any other pharmacological treatment, we observed no clinical difference between the two treatments in terms of completion of treatment, 16 studies 1381 participants, risk ratio (RR) 1.08 (95% confidence interval (CI) 0.97 to 1.21); number of participants abstinent at follow-up, three studies, 386 participants RR 0.98 (95% CI 0.70 to 1.37); degree of discomfort for withdrawal symptoms and adverse events, although it was impossible to pool data for the last two outcomes. These results were confirmed also when we considered the single comparisons: methadone with: adrenergic agonists (11 studies), other opioid agonists (eight studies), anxiolytic (two studies), paiduyangsheng (one study). Comparing methadone with placebo (two studies) more severe withdrawal and more drop-outs were found in the placebo group.   The results indicate that the medications used in the included studies are similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted. Data from literature are hardly comparable; programs vary widely with regard to the assessment of outcome measures, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long- acting opioids, can reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use.

Plain-language summary: For a tapered dose treatment to reduce withdrawal symptoms, illicit opioids are replaced by methadone or another agent using decreasing doses up to 30 days under medical supervision. The review authors searched the medical literature and identified 23 controlled trials involving 2467 adult opioid users in various countries. Trial participants were randomised to receive methadone or another pharmacological treatment. The other treatments were adrenergic agonists such as lofexidine, partial opioid agonists such as buprenorphine, opioid agonists such as LAAM (levo-α-acetyl-methadol) and the anxiolytics chlordiazepoxide and buspirone. In the two studies that compared methadone with placebo, withdrawal symptoms were more severe and more people dropped out in the placebo group. The studies included in this review confirmed that slow tapering with temporary substitution of long- acting opioids, could reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use. The medications used in the included studies were similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted. The programs varied widely with regard to the assessment of outcome measures. Seventeen of the included trials were conducted in inpatient settings.
Abstract: Nine studies (eight randomised controlled trials) involving 1109 participants met the inclusion criteria for the review. Antagonist-induced withdrawal is more intense but less prolonged than withdrawal managed with reducing doses of methadone, and doses of naltrexone sufficient for blockade of opioid effects can be established significantly more quickly with antagonist-induced withdrawal than withdrawal managed with clonidine and symptomatic medications. The level of sedation does not affect the intensity and duration of withdrawal, although the duration of anaesthesia may influence withdrawal severity. There is a significantly greater risk of adverse events with heavy, compared to light, sedation (RR 3.21, 95% CI 1.13 to 9.12, P = 0.03) and probably with this approach compared to other forms of detoxification. Heavy sedation compared to light sedation does not confer additional benefits in terms of less severe withdrawal or increased rates of commencement on naltrexone maintenance treatment. Given that the adverse events are potentially life-threatening, the value of antagonist-induced withdrawal under heavy sedation or anaesthesia is not supported. The high cost of anaesthesia-based approaches, both in monetary terms and use of scarce intensive care resources, suggest that this form of treatment should not be pursued.

Plain-language summary: The review of trials shows that this sort of withdrawal treatment is quicker than withdrawal managed with reducing doses of methadone or clonidine plus symptomatic medications. The intensity of withdrawal experienced with anaesthesia-based approaches is similar to that experienced with approaches using only minimal sedation, but there is a significantly increased risk of serious adverse events with anaesthesia-assisted approaches. The lack of additional benefit, and increased risk of harm, suggest that this form of treatment should not be pursued.
Abstract: We included fourteen studies. Duration ranged from very short (10 days) studies of the intramuscular preparation, to trials lasting over three months. For measures of global assessment, available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics we found no evidence of a difference in effectiveness (doctors' 4 RCTs n=150, RR 1.13, CI 0.69 to 1.86; nurses 4RCTs n=146, RR 1.23, CI 0.82 to 1.86). Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). The strength of the evidence relating to this compound is limited, owing to small sample size, poor study design, limited outcomes and incomplete reporting. Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). Data from this review suggest, at present, there is no evidence to suggest that it may have an atypical profile.

Plain-language summary: We included fourteen randomised controlled trials. When compared to other typical antipsychotics molindone shows no difference in effectiveness and is no more or less likely than typical drugs to cause movement disorders, it does however cause significantly more weight loss. At present there is no evidence to suggest that it may have an atypical profile.
Abstract: Fifty-five primary studies with 16,154 participants met the inclusion criteria. Long-term use of ICS (more than six months) did not consistently reduce the rate of decline in forced expiratory volume in one second (FEV1) in COPD patients (generic inverse variance analysis: mean difference (MD) 5.80 mL/year with ICS over placebo, 95% confidence interval (CI) -0.28 to 11.88, 2333 participants; pooled means analysis: 6.88 mL/year, 95% CI 1.80 to 11.96, 4823 participants), although one major trial demonstrated a statistically significant difference. There was no statistically significant effect on mortality in COPD patients (odds ratio (OR) 0.98, 95% CI 0.83 to 1.16, 8390 participants). Long-term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: MD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14, 2586 participants; pooled means analysis: MD -0.19 exacerbations per patient per year, 95% CI -0.30 to -0.08, 2253 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (MD -1.22 units/year, 95% CI -1.83 to -0.60, 2507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.65, 95% CI 2.03 to 3.46, 5586 participants) and hoarseness. In the long-term studies, the rate of pneumonia was increased in the ICS group compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.56, 95% CI 1.30 to 1.86, 6235 participants). The long-term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over three years. Patients and clinicians should balance the potential benefits of inhaled steroids in COPD (reduced rate of exacerbations, reduced rate of decline in quality of life and possibly reduced rate of decline in FEV1) against the potential side effects (oropharyngeal candidiasis and hoarseness, and risk of pneumonia).

Plain-language summary: Pooling of the data from the 55 trials with 16,154 people showed that there was no consistent long-term benefit in the rate of decline in breathing capacity. Death rates were unchanged. Inhaled steroids were beneficial in slowing down the rate of decline in quality of life and reducing the frequency of exacerbations. Inhaled steroids increased the risk of side effects including thrush (candida) infection in the mouth and hoarseness, and the rate of pneumonia. In deciding whether to use this treatment, consumers and health professionals should weigh up the benefits (reduced rate of exacerbations, reduced decline in quality of life and possible reduction in the rate of decline of breathing capacity) against the side effects (mouth thrush, hoarseness and increased risk of developing pneumonia).