GEM/cochrane-simplification huggingface dataset:
Abstract: Twelve trials including 754 participants met our inclusion criteria. Trials were from eight to 26 weeks in duration. We judged all trials to be at moderate or high risk of bias in at least some domains. Reporting of some risk of bias domains was poor. Our analyses comparing aerobic exercise to any active intervention showed no evidence of benefit from aerobic exercise in any cognitive domain. This was also true of our analyses comparing aerobic exercise to no intervention. Analysing only the subgroup of trials in which cardiorespiratory fitness improved in the aerobic exercise group showed that this improvement did not coincide with improvements in any cognitive domains assessed. Our subgroup analyses of aerobic exercise versus flexibility or balance interventions also showed no benefit of aerobic exercise in any cognitive domain. Dropout rates did not differ between aerobic exercise and control groups. No trial reported on adverse effects. Overall none of our analyses showed a cognitive benefit from aerobic exercise even when the intervention was shown to lead to improved cardiorespiratory fitness. We found no evidence in the available data from RCTs that aerobic physical activities, including those which successfully improve cardiorespiratory fitness, have any cognitive benefit in cognitively healthy older adults. Larger studies examining possible moderators are needed to confirm whether or not aerobic training improves cognition.

Plain-language summary: In this Cochrane Review, 12 trials including 754 participants met our inclusion criteria. Eight of the 12 trials reported that the aerobic exercise interventions resulted in increased fitness of the trained group. However, when we combined results across the trials, we did not find any significant benefits of aerobic exercise or increased fitness on any aspect of cognition. Many included trials had problems with their methods or reporting which reduced our confidence in the findings. We did not find evidence that aerobic exercise or increased fitness improves cognitive function in older people. However, it remains possible that it may be helpful for particular subgroups of people, or that more intense exercise programmes could be beneficial. Therefore further research in this area is necessary.
Abstract: For the first publication of this review, two RCTs involving 260 children with measles which compared vitamin A with placebo met the inclusion criteria. Neither study reported blindness or other ocular morbidities as end points. One trial of moderate quality suggested evidence of a significant increase in serum retinol levels in the vitamin A group one week after two doses of vitamin A (MD 9.45 µg/dL, 95% CI 2.19 to 16.71; 17 participants, moderate-quality evidence), but not six weeks after three doses of vitamin A (MD 2.56 µg/dL, 95% CI -5.28 to 10.40; 39 participants, moderate-quality evidence). There was no significant difference in weight gain six weeks (MD 0.39 kg, -0.04 to 0.82; 48 participants, moderate-quality evidence) and six months (MD 0.52 kg, 95% CI -0.08 to 1.12; 36 participants, moderate-quality evidence) after three doses of vitamin A. The second trial found no significant difference in serum retinol levels two weeks after a single dose of vitamin A (MD 2.67 µg/dL, 95% CI -0.29 to 5.63; 155 participants, moderate-quality evidence). Percentage of undernutrition between the two groups did not differ significantly at one week (RR 0.93, 95% CI 0.56 to 1.54, 145 participants) and two weeks (RR 0.82, 95% CI 0.52 to 1.29, 147 participants) after a single dose of vitamin A. No adverse event was reported in either study. We did not find any new RCTS for this second update. We did not find any trials assessing whether or not vitamin A supplementation in children with measles prevents blindness, as neither study reported blindness or other ocular morbidities as end points.

Plain-language summary: We included two randomised controlled trials of moderate quality, including 260 children with measles, comparing children given vitamin A with children not given vitamin A. The evidence is current to December 2015. Two doses of vitamin A given on two consecutive days to hospitalised children with measles led to an increase in the blood concentration of vitamin A after one week. However, there is a limitation in that neither of the two included studies reported blindness or other eye problems in children infected with measles. Also, no side effects of the treatment were reported in the included studies. We do not have sufficient evidence to demonstrate the benefit or otherwise of vitamin A in the prevention of blindness in children infected with measles. The quality of the evidence and methodology of both studies was moderate. The sample size of the included studies was relatively small, which could affect the accuracy of the results.
Abstract: Twenty randomized trials were identified of which thirteen were included in the quantitative analysis with data from 1022 subjects. Although all agents were better than placebo, parenteral high dose methotrexate (not included), sulfasalazine, azathioprine and etretinate were the agents that achieved statistical significance in a global index of disease activity (although it should be noted that only one component variable was available for azathioprine and only one trial was available for etretinate suggesting some caution is necessary in interpreting these results). Analysis of response in individual disease activity markers was more variable with considerable differences between different medications and responses. In all trials the placebo group improved over baseline (pooled improvement 0.39 DI units, 95% CI 0.26-0.54). There was insufficient data to examine toxicity. Parenteral high dose methotrexate and sulfasalazine are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition.

Plain-language summary: The objective was to assess the benefits of the treatment [sulfasalazine, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, methotrexate] for psoriatic arthritis and to assess the side effects. Parenteral methotrexate and sulfasalazine resulted in important benefit in over half the patients for psoriatic arthritis in these studies. There was insufficient data to evaluate other therapies and to examine toxicity. Further multicentre trials are required to establish the efficacy of azathioprine, oral methotrexate, etretinate, and colchicine.
Abstract: Seven studies were found to be suitable for inclusion from 33 identified as relevant. None of the trials provided adequate evidence to support the use of hydroxyurea owing to small sample size, large numbers of post-randomisation exclusions and questionable rules for censoring, particularly a failure to include treatment-related deaths in the survival analysis. Details of statistical analysis were limited and often confusing, and we felt meta-analysis would lead to unreliable and invalid conclusions. Most studies appeared to be double blind placebo-controlled studies but none give details of power calculations or reasons for stopping recruitment. Only two studies had more than 50 patients. Patients were excluded from analysis in most trials for treatment-related reasons; in one, less than half those recruited were used in the analysis, the remainder having been excluded because of tumour progression or treatment-related conditions e.g. septicaemia, worsening renal/hepatic function. In another trial five out of 20 in the hydroxyurea group died of treatment-related complications but the five-year survival group was presented as 94%. We found no evidence to support the use of hydroxyurea in addition to radiotherapy in the routine treatment of cervix cancer.

Plain-language summary: The orally-administered cytotoxic, hydroxyurea, may be given alongside radiotherapy for treating cervix cancer. Eight trials comparing concomitant hydroxyurea and radiotherapy with radiotherapy alone were assessed. They were not of sufficient quality to be able to pool the data. Although several trials reported an improvement in survival for patients receiving hydroxyurea, this conclusion was unreliable owing to methodological problems associated with trials including small sample size, a large number of patients excluded from analysis and questionable methods of analysis such as exclusion of treatment related deaths.
Abstract: Nine RCTs of mixed duration (3 days-52 weeks), recruiting 1175 participants were included (NYHA functional classes II-IV). Intravenous prostacyclin versus usual care (four studies) : There were significant improvements in exercise capacity of around 90 metres, cardiopulmonary haemodynamics and NYHA functional class over 3 days-12 weeks. Effects were consistent in primary and secondary pulmonary hypertension. Oral prostacyclin versus placebo (two studies) : Short-term data (3-6 months) indicated that there was a significant improvement in exercise capacity, but data from one study of 52 weeks reported no significant difference at 12 months. No significant differences were observed for any other outcome. Subcutaneous treprostinil versus placebo (two studies, 8-12 weeks):  One large study reported a significant median improvement in exercise capacity of around 16 metres. Cardiopulmonary haemodynamics and symptom scores favoured treprostinil. Infusion site pain and withdrawals due to adverse events were more frequent with treprostinil. Inhaled prostacyclin versus placebo (one study, 12 weeks):  There was a significant increase in exercise capacity of approximately 36 metres. Treatment led to better symptom scores and functional class status than with placebo. Subgroup analyses reported by individual studies showed a better exercise capacity in participants with PPH, than those participants with PH secondary to other diseases. Side effects and adverse events were common in the studies. There is evidence that intravenous prostacyclin in addition to conventional therapy at tolerable doses optimised by titration, can confer some short-term benefits (up to 12 weeks of treatment) in exercise capacity, NYHA functional class and cardiopulmonary haemodynamics. There is also some evidence that patients with more severe disease based upon NYHA functional class showed a greater response to treatment.

Plain-language summary: Prostacyclin may benefit patients with pulmonary hypertension (raised blood pressure in the lungs) in the short term but studies longer in duration are required. Pulmonary hypertension occurs when blood is pumped through arteries in the lungs at an increased pressure. The condition can lead to heart failure and death. Once the diagnosis is made, life expectancy ranges from a few months to a few years. Most current treatments apart from lung transplantation do not improve survival. Over an 8-12 week period prostacyclin improved exercise capacity and some measures of blood flow when given intravenously or via injection to patients with pulmonary hypertension. However, with intravenous administration there can be serious side effects as the drug has to be given continuously via a pump into a catheter placed into a central vein. It is not clear how long the drug continues to confer benefit without serious side effects. Prostacyclin can also be given by mouth, under the skin or through an inhaler. These forms of administration may be safer than intravenous prostacyclin and there is evidence that these may be effective in the short term.
Abstract: Three trials with a total of 245 participants were included in this review. The three trials directly compared the use of normal saline and heparin, however, between studies, all used different protocols for the standard and experimental arms with different concentrations of heparin and different frequency of flushes reported. In addition, not all studies reported on all outcomes. The quality of the evidence ranged from low to very low because there was no blinding, heterogeneity and inconsistency between studies was high and the confidence intervals were wide. CVC occlusion was assessed in all three trials (243 participants). We were able to pool the results of two trials for the outcomes of CVC occlusion and CVC-associated blood stream infection. The estimated rate ratio for CVC occlusion per 1000 catheter days between the normal saline and heparin group was 0.75 (95% CI 0.10 to 5.51, two studies, 229 participants, very low quality evidence). The estimated rate ratio for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37, two studies, 231 participants; low quality evidence). The duration of catheter placement was reported to be similar between the two study arms, in one study (203 participants). The review found that there was not enough evidence to determine the effects of intermittent flushing of heparin versus normal saline to prevent occlusion in long term central venous catheters in infants and children. Ultimately, if this evidence were available, the development of evidenced-based clinical practice guidelines and consistency of practice would be facilitated.

Plain-language summary: This review included randomised controlled trials, (clinical studies where people were randomly assigned into one of two or more treatment groups), that compared the use of saline and heparin to prevent blockage, and other complications related to long term catheters. The evidence is current to April 2015. Two review authors independently reviewed the studies. Three studies with a total of 245 participants were included in the review. The three trials directly compared the use of saline and heparin, however, between studies, all were very different in the way they compared saline and heparin, with different concentrations of heparin and different frequency of flushes reported. We were able to combine the results of two studies; the analysis showed imprecise results for the blocking of catheters and blood stream infections between normal saline and heparin. One study reported the duration of catheter placement to be similar between the two study arms. The overall quality of the evidence ranged from low to very low. There was high risk of bias for blinding, there were differences between the studies methods and interventions, inconsistent results between the studies, and not all studies reported all outcomes of interest. We found there was not enough evidence to determine which solution, heparin or saline, is more effective for reducing complications. Further research is required and is likely to have an important impact in this area.
Abstract: In total, we identified 1298 publications through the search strategy. We included 28 publications reporting on 24 studies. COC users were at increased risk of myocardial infarction or ischemic stroke compared with non-users: relative risk (RR) 1.6 (95% CI 1.3-1.9).These RRs were similar for myocardial infarction (1.6, 95% CI 1.2 to 2.1) and ischemic stroke (1.7, 95% CI 1.5 to 1.9). The risks did not vary clearly according to the generation of progestagen or according to progestagen type. When we stratified preparations according to estrogen dose, the risk of myocardial infarction or ischemic stroke seemed to increase with higher doses of estrogen. This meta-analysis showed that the risk of myocardial infarction or ischemic stroke was 1.6-fold increased in women using COCs . The risk was highest for pills with > 50 microgram estrogen. When combined with the results of studies on the risk of venous thrombosis in COC users, it seems that the COC pill containing levonorgestrel and 30 µg of estrogen is the safest oral form of combined oral hormonal contraception.

Plain-language summary: In total, 28 articles on 24 unique studies met the inclusion criteria. Our results showed that the overall risk of arterial thrombosis was was 1.6-fold increased in women using oral contraceptive pills compared with women who did not use oral contraceptive pills. The risk did not vary clearly according to progestagen type. However, we found that the risk of arterial thrombosis seemed to be twice as high in women taking pills with higher doses of estrogen. Also, the risk of other side effects of oral contraceptive pills (such as a blood clot in a vein-venous thrombosis) should be considered before any type of oral contraceptive pill is prescribed. It is likely that the COC pill containing levonorgestrel and 30 µg of estrogen is the safest oral form of combined oral hormonal contraception. The overall quality of evidence in this review was moderate. Most studies (22 out of 28) correctly confirmed that patients had been diagnosed with arterial thrombosis. However, only four studies also checked that the type of pill a patient had been using was reported correctly. In addition, only half of the studies ensured that the correct comparisons were made between patients with and patients without arterial thrombosis. Also of importance is the fact that the analysis on progestagen type was based on few studies only.
Abstract: We found three relevant small, short trials (total n=126). Clinical Global Impression data were equivocal (n=27, 1 RCT, WMD -0.43 CI -0.9 to 0.1). Average total PANSS scores were not significantly different between the DHEA plus antipsychotic group and those given antipsychotic drugs and placebo (n=82, 2 RCTs, WMD -4.16 CI -13.8 to 5.5). PANSS positive scores were equivocal (n=55, 1 RCT, WMD -1.00 CI -3.8 to 1.8). For negative symptoms binary SANS scale data favoured the DHEA plus antipsychotic group (n=30, 1 RCT, RR 0.23 CI 0.1 to 0.6, NNT 2 CI 2 to 3) but PANSS negative scores were not significantly different between comparison groups (n=55, 1 RCT, WMD -2.30 CI -6.4 to 1.8). About 17% of people left both groups early (n=64, 2 RCTs, RR 0.80 CI 0.3 to 2.4). St Hans Rating Scale data for extrapyramidal symptoms favoured the DHEA plus antipsychotic group (n=30, 1 RCT, WMD -5.00 CI -8.8 to -1.2) but akathisia ratings were equivocal (n=34, 1 RCT, RR 2.67 CI 0.3 to 23.1). Ratings of parkinsonian movement disorder differed within the same trial depending of the outcome scale used. Quality of life seemed unaffected by use of DHEA (n=55, 1 RCT, WMD 6.20 CI -1.4 to 13.8). Results are inconclusive with most outcomes being either non-significant or producing contradictory findings. Currently, adjunctive DHEA should remain an experimental treatment for people with schizophrenia.

Plain-language summary: We reviewed the effects of dehydroepiandrosterone (DHEA)/testosterone as an adjunctive therapy to standard antipsychotic drugs for people with schizophrenia and found three relevant small, short studies. All trials compared antipsychotic drugs plus DHEA with antipsychotic drugs and placebo. Results are inconclusive, with most outcomes being either non-significant or contradictory and a much larger, conclusive study should be undertaken. Currently however, people with schizophrenia should only agree to take this experimental treatment within the context of a well designed experimental study. We found nothing in these studies to suggest that it should be used in routine care.
Abstract: Two randomized controlled trials enrolling a total of 268 patients satisfied the inclusion criteria. The risk of bias for Drewry 1994 was unclear as this study was presented as an abstract, while Bennett 2003 was rated as at low risk. Pooling of data was not possible. In one study there was no evidence of improved effectiveness with the addition of a non-steroidal anti-inflammatory drug (tenoxicam) to routine recompression therapy (at six weeks: relative risk (RR) 1.04, 95% confidence interval (CI) 0.90 to 1.20, P = 0.58) but there was a reduction in the number of compressions required when tenoxicam was added from three to two (P = 0.01, 95% CI 0 to 1). In the other study, the odds of multiple recompressions were lower with a helium and oxygen (heliox) table compared to an oxygen treatment table (RR 0.56, 95% CI 0.31 to 1.00, P = 0.05). Recompression therapy is standard for the treatment of DCI, but there is no randomized controlled trial evidence for its use. Both the addition of a non-steroidal anti-inflammatory drug (NSAID) and the use of heliox may reduce the number of recompressions required, but neither improve the odds of recovery. The application of either of these strategies may be justified. The modest number of patients studied demands a cautious interpretation. Benefits may be largely economic and an economic analysis should be undertaken. There is a case for large randomized trials of high methodological rigour in order to define any benefit from the use of different breathing gases and pressure profiles during recompression therapy.

Plain-language summary: This review found only two randomized trials enrolling a total of 268 patients. One trial compared standard oxygen recompression to helium and oxygen recompression, while the other compared oxygen recompression alone to recompression and an adjunctive non-steroidal anti-inflammatory drug (NSAID). Both trials suggested that these additional interventions may shorten the course of recompression required. For example, the use of an NSAID reduced the median number of recompression sessions required from three to two. We conclude that there is little evidence for using one recompression strategy over another in the treatment of decompression illness and that the addition of an anti-inflammatory drug may shorten the course of recompression required. More research is needed.
Abstract: We included one trial with 226 participants: A Randomized trial of Unruptured Brain Arteriovenous Malformations (ARUBA), comparing intervention versus conservative management for unruptured brain AVMs (that had never bled). The quality of evidence was moderate because we found just one trial that was at low risk of bias other than a high risk of performance bias due to participants and treating physicians not being blinded to allocated treatment. Data on functional outcome and death at a follow-up of 12 months were provided for 218 (96%) of the participants in ARUBA. In this randomized controlled trial (RCT), intervention compared to conservative management increased death or dependency (modified Rankin Scale score ≥ 2, risk ratio (RR) 2.53, 95% confidence interval (CI) 1.28 to 4.98; 1 trial, 226 participants; moderate-quality evidence) and the proportion of participants with symptomatic intracranial haemorrhage (RR 6.75, 95% CI 2.07 to 21.96; 1 trial, 226 participants; moderate-quality evidence), but there was no difference in the frequency of epileptic seizures (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 226 participants; moderate-quality evidence). Three RCTs are ongoing. We found moderate-quality evidence from one RCT including adults with unruptured brain AVMs that conservative management was superior to intervention with respect to functional outcome and symptomatic intracranial haemorrhage over one year after randomization. More RCTs will help to confirm or refute these findings.

Plain-language summary: We found one published randomized controlled trial, including 226 adults. We found moderate-quality evidence of harm (stroke due to bleeding in the brain, and death or dependency) over one year of follow-up from interventional treatments compared to conservative management for adults who had a brain AVM that had never bled. The long-term risks are unknown. Overall, the quality of the evidence was moderate because there was just one trial and it did not use blinding. More information will become available from the three trials that are ongoing.