GEM/cochrane-simplification huggingface dataset:
Abstract: Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance. With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84). No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended.

Plain-language summary: In the current review, data were found and analysed from 7 trials involving 404 patients randomly allocated to receive antibiotics or placebo. Although death occurred less after antibiotics (8.4%) than placebo (14.4%), as did infected pancreatic necrosis (19.7% versus 24.4%) and other infections (23.7% versus 36%), the differences were not statistically significant and so genuine benefit cannot be confirmed. There were no major problems with antibiotic resistance, and fungal infections were similar (3.9% versus 5%). The quality of studies was variable and only two were ‘blinded’, whereby investigators and patients were unaware of which treatment patients received. Many different regimens were used, and of the two main types of antibiotics used, a beta-lactam appeared to work better. Only one type of antibiotic (imipenem) was considered on its own, showing a significant decrease in infection of the pancreatic necrosis. Although we cannot confirm benefit from the use of prophylactic antibiotics in this condition, consistent trends towards a beneficial effect nevertheless remain. Further, better designed studies, ideally with beta-lactam antibiotics, are required.
Abstract: Searches identified 23 trials; nine trials (255 participants) are included, of these seven trials are more than 10 years old. Three trials of nebulized thiol derivatives were identified (one compared 20% N-acetylcysteine to 2% N-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. Six trials of oral thiol derivatives were identified. Three trials compared N-acetylcysteine to placebo; one compared N-acetylcysteine, ambroxol and placebo; one compared carbocysteine to ambroxol; and one compared low and high-dose N-acetylcysteine. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.

Plain-language summary: Six included trials assessed the effects of oral thiol derivatives.Three of these trials compared oral N-acetylcysteine to placebo; one compared oral N-acetylcysteine, oral ambroxol and placebo; and one compared oral carbocysteine and oral ambroxol (no placebo). None of the trials showed an overall significant benefit in any of the outcome measures of this review. Oral thiol derivatives were generally well-tolerated with no major adverse effects. In summary, the trials included in the review did not provide any evidence that nebulized or oral thiol derivatives were either beneficial or harmful to people with cystic fibrosis. Further research investigating the effects of thiol derivatives in people with cystic fibrosis is required before their use can be recommended.
Abstract: Eight trials involving around 1100 people were included but data were only available for 1036 women in seven trials, of whom 526 received urodynamics. There was some evidence of risk of bias. The four deaths and 12 dropouts in the control arm of one trial were unexplained. There was significant evidence that the tests did change clinical decision making. Women in the urodynamic arms of three trials were more likely to have their management changed (proportion with change in management compared with the control arm 17% versus 3%, risk ratio (RR) 5.07, 95% CI 1.87 to 13.74), although there was statistical heterogeneity. There was evidence from two trials that women treated after urodynamic investigations were more likely to receive drugs (RR 2.09, 95% CI 1.32 to 3.31). On the other hand, in five trials women undergoing treatment following urodynamic investigation were not more likely to undergo surgery (RR 0.99, 95% CI 0.88 to 1.12). There was no statistically significant difference however in the number of women with urinary incontinence if they received treatment guided by urodynamics (37%) compared with those whose treatment was based on history and clinical findings alone (36%) (for example, RR for the number with incontinence after the first year 1.02, 95% CI 0.86 to 1.21). It was calculated that the number of women needed to treat was 100 women (95% CI 86 to 114 women) undergoing urodynamics to prevent one extra individual being incontinent at one year. One trial reported adverse effects and no significant difference was found (RR 1.10, 95% CI 0.81 to 1.50). While urodynamic tests did change clinical decision making, there was some evidence that this did not result in better outcomes in terms of a difference in urinary incontinence rates after treatment. There was no evidence about their use in men, children, or people with neurological diseases. Larger definitive trials are needed in which people are randomly allocated to management according to urodynamic findings or to management based on history and clinical examination to determine if performance of urodynamics results in higher continence rates after treatment.

Plain-language summary: Eight trials were found, which included around 1100 people, although information was only available for 1036 women. There was not enough evidence to determine whether the urodynamic tests led to better outcomes. There was some evidence that urodynamic testing increased the number of people given drugs but not the number of people undergoing surgery. This did not result in any difference in the number of people who leaked urine, and it was not known whether they had a better quality of life. More research is needed in which people are randomised to having treatment decisions based on either their symptoms and examination alone or after taking into account the extra information provided by urodynamic tests.
Abstract: We found 14 relevant studies, mostly of short duration, poorly reported and conducted in the 1970s (total n=794 participants). Nine of these compared oral formulations of both compounds, and five compared intramuscular formulations. Haloperidol was associated with significantly fewer people leaving the studies early (13 RCTs, n=476, RR 0.26 CI 0.08 to 0.82). The efficacy outcome 'no significant improvement' tended to favour haloperidol, but this difference was not statistically significant (9 RCTs, n=400, RR 0.81 CI 0.64 to 1.04). Movement disorders were more frequent in the haloperidol groups ('at least one extrapyramidal side effect': 6 RCTs, n=37, RR 2.2 CI 1.1 to 4.4, NNH 5 CI 3 to 33), while chlorpromazine was associated with more frequent hypotension (5 RCTs, n=175, RR 0.31 CI 0.11 to 0.88, NNH 7 CI 4 to 25). Similar trends were found when studies comparing intramuscular formulations and studies comparing oral formulations were analysed separately. Given that haloperidol and chlorpromazine are global standard antipsychotic treatments for schizophrenia, it is surprising that less than 800 people have been randomised to a comparison and that incomplete reporting still makes it difficult for anyone to draw clear conclusions on the comparative effects of these drugs. However, it seems that haloperidol causes more movement disorders than chlorpromazine, while chlorpromazine is significantly more likely to lead to hypotonia. We are surprised to have to say that we feel further, large, well designed, conducted and reported studies are required.

Plain-language summary: Overall the mental health and general functioning of people taking chlorpromazine or haloperidol improved. Compared to nowadays fewer people in both arms of the trial left the study early but those taking chlorpromazine were statistically more likely to do so. This was also the case when the oral medications were analysed on their own, but not in the case of the injected form. There was a suggestion that people may leave the study because of either adverse events or because the treatment did not work well. Haloperidol had statistically more movement side effects while chlorpromazine was statistically more likely to cause low blood pressure (hypotension). Although these trials show both haloperidol and chlorpromazine to be effective drugs for schizophrenia, a lot of data were not able to be used because some measures were not reported. Therefore the area would benefit from a new trial with a large number of people and lasting at least a year. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).
Abstract: Twenty one trials involving 7243 participants were included. Equal daily doses of ciclesonide and beclomethasone (BDP) or budesonide (BUD) gave similar results for peak expiratory flow rates (PEF), although forced vital capacity (FVC) was higher with ciclesonide. Data on forced expired volume in one second (FEV1) were inconsistent. Withdrawal data and symptoms were similar between treatments. Compared with the same dose of fluticasone (FP), data on lung function parameters (FEV1, FVC and PEF) did not differ significantly. Paediatric quality of life score favoured ciclesonide. Candidiasis was less frequent with ciclesonide, although other side-effect outcomes did not give significant differences in favour of either treatment. When lower doses of ciclesonide were compared to BDP or BUD, the difference in FEV1 did not reach significance but we cannot exclude a significant effect in favour of BDP/BUD. Other lung function outcomes did not give significant differences between treatments. Paediatric quality of life scores did not differ between treatments. Adverse events occurred with similar frequency between ciclesonide and BDP/BUD. Comparison with FP at half the nominal dose was undertaken in three studies, which indicated that FEV1 was not significantly different, but was not equivalent between the treatments (per protocol: -0.05 L 95% confidence intervals -0.11 to 0.01). The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Plain-language summary: This findings of this review of 21 trials (7243 participants) do not allow certainty about the relative efficacy of ciclesonide compared to older inhaled corticosteroids, especially at higher doses. The results of the review to date do not indicate whether ciclesonide provides a significantly more useful safety profile that other inhaled corticosteroids at similar equivalent doses. However, the finding of lower oral candidiasis in patients treated with ciclesonide compared to fluticasone may be important for those patients who experience oral thrush with their current ICS. In addition, further studies in children are required to obtain data on the side-effect profile of ciclesonide in this population.
Abstract: Administration of dexamethasone prior to extubation significantly reduced the need for reintubation of the trachea. This result applies to both the high-risk group and to the total population of infants enrolled. However, the incidence of extubation failure was zero in the trial that attempted to exclude infants at high risk of airway edema. The side effects of higher blood sugar levels and glycosuria were found in the two trials where these were sought. Implications for practice  Dexamethasone reduces the need for endotracheal reintubation of neonates after a period of IPPV. In view of the lack of effect in low-risk infants and the documented and potential side effects, it appears reasonable to restrict its use to infants at increased risk for airway edema and obstruction, such as those who have received repeated or prolonged intubations. Implications for research  Issues of dosage and applicability to the extremely low birthweight population could be addressed in future trials. Outcomes such as chronic lung disease, duration of assisted ventilation and length of hospital stay as well as long-term neurodevelopment should also be examined.

Plain-language summary: This review found that giving dexamethasone (a corticosteroid drug) around the time of extubation can help prevent swelling in the baby's throat that might require reinsertion of the tube. However, the review found that there are adverse effects of dexamethasone. The benefits only outweigh the risks for babies at high risk of complication (such as those who have received several, or prolonged, intubations).
Abstract: We included 12 new RCTs for this update, giving a total of 39 RCTs (6013 participants). These additional 12 RCTs have not changed the original conclusions about the clinical efficacy of minocycline. The identified RCTs were generally small and poor quality. Meta-analysis was rarely possible because of the lack of data and different outcome measures and trial durations. Although minocycline was shown to be an effective treatment for moderate to moderately-severe acne vulgaris, there was no evidence that it is better than any of the other commonly-used acne treatments. One company-sponsored RCT found minocycline to be less effective than combination treatment with topical erythromycin and zinc. No trials have been conducted using minocycline in those participants whose acne is resistant to other therapies. Also, there is no evidence to guide what dose should be used. The adverse effects studies must be interpreted with caution. The evidence suggests that minocycline is associated with more severe adverse effects than doxycycline. Minocycline, but not other tetracyclines, is associated with lupus erythematosus, but the risk is small: 8.8 cases per 100,000 person-years. The risk of autoimmune reactions increases with duration of use. The evidence does not support the conclusion that the more expensive extended-release preparation is safer than standard minocycline preparations. Minocycline is an effective treatment for moderate to moderately-severe inflammatory acne vulgaris, but there is still no evidence that it is superior to other commonly-used therapies. This review found no reliable evidence to justify the reinstatement of its first-line use, even though the price-differential is less than it was 10 years ago. Concerns remain about its safety compared to other tetracyclines.

Plain-language summary: In summary, there is no evidence to support the first-line use of minocycline in the treatment of acne. All of the trials showed that, on average, people treated with minocycline experienced an improvement in their acne. However, no study conclusively showed any important clinical difference between minocycline or other commonly-used therapies. The analysis found that minocycline may act more quickly than oxytetracycline or tetracycline, but there is no overall difference in the end. There is no evidence that it is more effective in acne that is resistant to other therapies, or that the effects last longer. Although it is often claimed that the more expensive once-daily slow-release preparation is a more attractive option to teenagers with acne, the evidence in this review does not show it to be any better or safer compared to other oral antibiotics that have to be taken more frequently. Despite a thorough search for evidence, it is still not known which of the tetracyclines are the safest to take overall as they are all associated with side-effects. The only conclusion that we could make was that people treated with minocycline for acne are at a significantly greater risk of developing an autoimmune (lupus-like) syndrome than those given tetracycline or no treatment.
Abstract: We included 15 trials with 6515 patients. The median follow up was six years. Tumour sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (UICC 2002). There was a significant survival benefit with altered fractionation radiotherapy, corresponding to an absolute benefit of 3.4% at five years (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.97; P = 0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at five years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at five years, P = 0.02). There was a benefit in locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at five years; P < 0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (under 50 year old) (HR 0.78, 95% CI 0.65 to 0.94), 0.95 (95% CI 0.83 to 1.09) for 51 to 60 year olds, 0.92 (95% CI 0.81 to 1.06) for 61 to 70 year olds, and 1.08 (95% CI 0.89 to 1.30) for those over 70 years old; test for trends P = 0.007). Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress.

Plain-language summary: This Cochrane Review is an individual patient data based meta-analysis and the aim was to assess whether this type of radiotherapy could improve survival. We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck cancers and grouped trials into three pre-specified categories: hyperfractionated, accelerated without total dose reduction and accelerated with total dose reduction. The results of this meta-analysis suggest that altered fractionation radiotherapy improves survival in patients with head and neck cancer. Comparison of the different types of altered fractionation radiotherapy suggests that hyperfractionation provides the greatest benefit. Individual patient data meta-analysis is a long process and this review included all eligible trials which had completed recruiting patients by 1998. A major update of the analysis, including data from more recent trials, is currently underway.
Abstract: Five primary studies that collectively researched a total of 725 women living with HIV were analysed. When compared to standard care or minimal HIV support intervention, meta-analysis showed that behavioral interventions had no effect on increasing condom use among HIV-positive women. This finding was consistent at 3 (OR= 0.72; 95% CI 0.43-1.20; p=0.21), 6 (OR= 0.96; 95% CI 0.66-1.40; p=0.83) and 12-months follow-up meetings (OR= 0.75; 95% CI 0.51-1.11; p=0.15). Only one study presented adequate data to analyze the relationship between behavioral interventions and STI incidence. Studies included in this analysis demonstrated low risk of bias based on the risk of bias criteria. However, sample size was considered inadequate across all studies. Meta-analysis shows that behavioral interventions have little effect on increasing condom use among HIV-positive women. However, these findings should be used with caution since results were based on a few small trials that were targeted specifically towards HIV-positive women. To decrease sexual transmission of HIV among this population, we recommend interventions that combine condom promotion, family planning provision and counselling, and efforts to reduce viral loads among HIV-positive women and their partners (e.g., HAART treatment provision). New research is needed to address the needs of HIV-positive women, including an assessment of the impact of interventions that combine safer sexual behavior and harm reduction approaches.

Plain-language summary: This systematic review of randomized controlled trials assessed the effects of behavioral interventions on promoting condom use among women living with HIV, a population at higher risk to other sexually transmitted infections (STIs). Based on five eligible studies, we found that behavioral interventions promoting consistent condom use in HIV-positive women did not have a significant impact on outcomes, when compared to standard care or minimal HIV-related support. However, these findings should be used with caution since they are based on a few small trials that were targeted specifically towards HIV-positive women. New research is needed to assess the potential personal and public health gains that could arise from a combination of interventions that promote safe sexual behavior and adopt a harm reduction approach, particularly in developing countries, where HIV infection rates among women remain high.