GEM/cochrane-simplification huggingface dataset:
Abstract: One new study has been identified and included in this update. In total, 13 studies involving 4122 participants were included in this review update. Years of publication ranged from 1971 to 2011. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio (OR) 0.43, 95% confidence interval (CI) 0.32 to 0.59; P < 0.00001) and total mortality (OR 0.57, 95% CI 0.42 to 0.78; P = 0.0004). Aspirin and dipyridamole reduced these events similarly. The risk of major bleeding was increased when antiplatelet agents were added to oral anticoagulants (OR 1.58, 95% CI 1.14 to 2.18; P = 0.006). For major bleeding, there was no evidence of heterogeneity between aspirin and dipyridamole and in the comparison of trials performed before and after 1990, around the time when anticoagulation standardisation with the international normalised ratio was being implemented. A lower daily dose of aspirin (< 100 mg) may be associated with a lower major bleeding risk than higher doses. Adding antiplatelet therapy, either dipyridamole or low-dose aspirin, to oral anticoagulation decreases the risk of systemic embolism or death among patients with prosthetic heart valves. The risk of major bleeding is increased with antiplatelet therapy. These results apply to patients with mechanical prosthetic valves or those with biological valves and indicators of high risk such as atrial fibrillation or prior thromboembolic events. The effectiveness and safety of low-dose aspirin (100 mg daily) appears to be similar to higher-dose aspirin and dipyridamole. In general, the quality of the included trials tended to be low, possibly reflecting the era when the majority of the trials were conducted (1970s and 1980s when trial methodology was less advanced).

Plain-language summary: This updated review of 13 trials found that oral anticoagulation and antiplatelet drugs were more effective than anticoagulation alone. The addition of antiplatelet drugs to anticoagulants increases the risk of bleeding by about 50%. Low-dose aspirin (less than 100 mg daily) may be associated with the lowest risk of bleeding. However, in general the quality of the included trials tended to be low, possibly reflecting the era when the majority of the trials were conducted (1970s and 1980s when trial methodology was less advanced).
Abstract: Two trials with a total of 298 participants met the inclusion criteria. Both compared timed voiding plus additional intervention with usual care. In one of these timed voiding was combined with continence products, placement of a bedside commode for each participant, education to staff on transfer techniques, feedback and encouragement to staff, praise to participants for "successful responses" and administration of oxybutynin in small doses. The mean percentage who were incontinent when checked daily was 20% in the intervention group compared with 80% in the control group. No further between group analysis was possible from the data reported. The other trial combined timed voiding with a medical assessment and individualised medical management that was based on clinical data. Reduction in the number of participants with daytime and night-time incontinence was greater in the intervention group but this difference was statistically significant only for night-time wetting. There was no difference in the volume of urine lost as determined by pad weighing. The methodological quality of these trials was not high based on the quality appraisal criteria of the Cochrane Incontinence Group. In particular, there was a lack of clarity regarding levels of blinding. It was not possible to combine data from trials. In both trials, the fixed schedule of toileting was combined with other interventions. The extent to which the results reflect the contribution of timed voiding is unknown because the trials' design did not allow assessment of the effects of the fixed schedule of toileting separately from other components of the interventions. The data were too few and of insufficient quality to provide empirical support for or against the intervention of timed voiding.

Plain-language summary: This review examined the use of a fixed interval of voiding for the management of urinary incontinence in adults. This approach to urinary incontinence is thought to be common in aged care homes for people who require assistance from other people for toileting and continence care. The reviewers found two trials that had evaluated timed voiding. They included 298 elderly women who were living in aged care homes and had reduced cognition and impaired mobility. Reductions in the number of incontinence episodes were reported in each trial. The reviewers found insufficient data for these findings to be combined. Hence, at this point in time, there is not enough evidence on the effects of timed voiding for the management of urinary incontinence.
Abstract: 123 reports from 30 studies (4102 patients) were included. At six months graft loss was significantly reduced in tacrolimus-treated recipients (RR 0.56, 95% CI 0.36 to 0.86), and this effect was persistent up to three years. Meta-regression showed that this benefit diminished as higher trough levels of tacrolimus were targeted (P = 0.04), after allowing for differences in cyclosporin formulation (P = 0.97) and cyclosporin target trough level (P = 0.38). At one year, tacrolimus patients suffered less acute rejection (RR 0.69, 95% CI 0.60 to 0.79), and less steroid-resistant rejection (RR 0.49, 95% CI 0.37 to 0.64), but more insulin-requiring diabetes mellitus (RR 1.86, 1.11 to 3.09), tremor, headache, diarrhoea, dyspepsia and vomiting. Cyclosporin-treated recipients experienced significantly more constipation and cosmetic side-effects. We demonstrated no differences in infection or malignancy. Tacrolimus is superior to cyclosporin in improving graft survival and preventing acute rejection after kidney transplantation, but increases post-transplant diabetes, neurological and gastrointestinal side effects. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid 12 suffering acute rejection, two losing their graft but cause an extra five to become insulin-requiring diabetics.

Plain-language summary: This review compared tacrolimus and cyclosporin used as primary immunosuppression for kidney transplant recipients. Thirty studies (4102 patients) were included. Tacrolimus was shown to be superior to cyclosporin in improving graft survival and preventing acute rejection after kidney transplantation, but increases post-transplant diabetes, neurological and gastrointestinal side effects. There was insufficient information to assess the cost of tacrolimus versus cyclosporin, and there was a general failure to consider global quality of life (QOL) for transplant recipients which may inform our understanding of patient preference and compliance.
Abstract: We identified 45 trials, of which eight trials (356 participants) comparing a single anti-pseudomonal agent to a combination of the same antibiotic and one other, were included. There was a wide variation in the individual antibiotics used in each trial. In total, the trials included seven comparisons of a beta-lactam antibiotic (penicillin-related or third generation cephalosporin) with a beta-lactam-aminoglycoside combination and three comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination. These two groups of trials were analysed as separate subgroups. There was considerable heterogeneity amongst these trials, leading to difficulties in performing the review and interpreting the results. The meta-analysis did not demonstrate any significant differences between monotherapy and combination therapy, in terms of lung function; symptom scores; adverse effects; and bacteriological outcome measures. These results should be interpreted cautiously. Six of the included trials were published between 1977 and 1988; these were single-centre trials with flaws in the randomisation process and small sample size. Overall, the methodological quality was poor. The results of this review are inconclusive. The review raises important methodological issues. There is a need for an RCT which needs to be well-designed in terms of adequate randomisation allocation, blinding, power and long-term follow up. Results need to be standardised to a consistent method of reporting, in order to validate the pooling of results from multiple trials.

Plain-language summary: We included eight trials with a total of 356 people. Six of these were published before 1988, were each based in a single centre and used a range of different drugs. These factors made it difficult to combine and analyse the results. We did not find any differences between the two therapies for lung function, symptom scores, side effects or bacteriological outcome measures. We conclude that there is not enough evidence to compare the different therapies. More research is needed, particularly looking at side effects of treatment. Six of the included trials were quite old (published between 1977 and 1988). They did not include many people and had flaws in the way the people taking part were put into the different treatment groups. Overall, the quality of the trials' design was poor.
Abstract: We included three randomised trials with 170 participants. Ninety participants were randomised to the Chinese herbal medicines groups and 80 to the comparator groups with numbers ranging from 50 to 60 participants per trial. The duration of treatment varied from four to six weeks. All the included trials were conducted in China and published in Chinese. Overall, the risk of bias of included trials was unclear. There were no outcome data in any of the trials on death from any cause, cardiovascular or cerebrovascular events, health-related quality of life, or costs. Three different herbal medicines, including Zhusuan Huoxue decoction, Huoxue Huayu Tongluo decoction, and Chushi Huayu decoction were evaluated. All three trials investigating Chinese herbal medicines treatment alone (two studies) or in combination with gemfibrozil (one study) reported results on serum triglyceride (TG) in favour of the herbal treatment. We did not perform a meta-analysis due to significant clinical heterogeneity between the studies. No relevant differences in adverse effects occurred and no serious adverse events were noted. The present systematic review suggests that Chinese herbal medicines may have positive effects on hypertriglyceridaemia. The trials did not report serious adverse effects following Chinese herbal medicines treatment. However, based on an unclear risk of bias in included studies and lack of patient-important long-term outcomes, no definite conclusion could be reached.

Plain-language summary: To evaluate the effects of various herbal formulations (including single herbs, Chinese proprietary medicines, and mixtures of different herbs) for treating hypertriglyceridaemia, we examined all available randomised controlled trials of Chinese herbal medicines. We identified three studies lasting from four to six weeks and recruiting 170 participants with hypertriglyceridaemia. There were no data on death from any cause, cardiovascular or cerebrovascular events (such as heart attacks or strokes), health-related quality of life, or costs. We found that Chinese herbal medicines used alone or in combination with lipid-lowering drugs or 'life style' changes may have positive effects on reducing the blood levels of triglycerides. No relevant differences in adverse effects occurred and no serious adverse events were noted. On the basis of the current evidence, no definite conclusion is possible especially because of the unclear risk of bias in the included studies and lack of reporting on patient-important long-term outcomes.
Abstract: We found no studies that satisfied the inclusion criteria. Based on this review, we are unable to make any new recommendations on the use of adrenaline for the treatment of anaphylaxis. Although there is a need for randomized, double-blind, placebo-controlled clinical trials of high methodological quality in order to define the true extent of benefits from the administration of adrenaline in anaphylaxis, such trials are unlikely to be performed in individuals with anaphylaxis. Indeed, they might be unethical because prompt treatment with adrenaline is deemed to be critically important for survival in anaphylaxis. Also, such studies would be difficult to conduct because anaphylactic episodes usually occur without warning, often in a non-medical setting, and differ in severity both among individuals and from one episode to another in the same individual. Consequently, obtaining baseline measurements and frequent timed measurements might be difficult, or impossible, to obtain. In the absence of appropriate trials, we recommend, albeit on the basis of less than optimal evidence, that adrenaline administration by intramuscular (i.m.) injection should still be regarded as first-line treatment for the management of anaphylaxis.

Plain-language summary: We therefore conducted a systematic review of the literature searching key databases for high quality published and unpublished material on the use of adrenaline for emergency treatment; in addition, we contacted experts in this area and the relevant pharmaceutical companies. Our searches retrieved no randomized controlled trials on this subject. We concluded that the use of adrenaline in anaphylaxis is based on tradition and on evidence from fatality series in which most individuals dying from anaphylaxis had not received prompt adrenaline treatment. Adrenaline appears to be life saving when injected promptly, however, there is no evidence from randomized controlled trials for or against the use of adrenaline in the emergency treatment of anaphylaxis. Given the infrequency of anaphylaxis, its unpredictability and the speed of onset of reactions, conducting such trials is fraught with ethical and methodological difficulties.
Abstract: Three randomised controlled trials were found comparing amantadine with placebo in the treatment of dyskinesia in patients with idiopathic Parkinson's disease. Three trials were excluded on the basis that they had no control group and a further three did not state whether they randomised the treatment that participants received. The included trials were double-blind cross-over studies involving a total of 53 patients. All three studies failed to present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. Two trials had no wash-out interval between the treatment periods. In view of the risk of a carry-over effect into the second arm, the results of these trials were not analysed. The final trial had a one week wash-out interval but only examined 11 participants. One study reported side-effects of amantadine in 8 of the 18 participants, including confusion and worsening of hallucinations. Another reported reversible edema of both feet in one of eleven participants. Due to lack of evidence it is impossible to determine whether amantadine is a safe and effective form of treatment for levodopa-induced dyskinesias in patients with Parkinson's disease.

Plain-language summary: This review found that there is not enough evidence from trials about the effects of amantadine for people with dyskinesia in Parkinson's disease. Adverse effects in trials so far have included confusion, worsening of hallucinations, the re-emergence of palpitations, nausea, dry mouth, swelling of feet and constipation.
Abstract: Nine studies representing 7960 women met our inclusion criteria, including seven randomised controlled trials and two controlled before and after studies that reported IUD uptake postintervention. We evaluated the quality of evidence as moderate to low. Three studies on contraceptive counselling and referrals by community workers showed an increase in uptake of the IUD among intervention groups (Peto OR 2.00; 95% CI 1.40 to 2.85). Two studies on antenatal contraceptive counselling also favoured the intervention groups (Peto OR 2.33; 95% CI 1.39 to 3.91). One study on postnatal couple contraceptive counselling also showed an increase in IUD uptake compared to control (Peto OR 5.73; 95% CI 3.59 to 9.15). The results of one study evaluating postnatal home visits and two studies on enhanced postabortion contraceptive counselling did not reach statistical significance. Community-based interventions and antenatal contraceptive counselling improved uptake of copper IUD contraception. Since the copper IUD is one of the most effective reversible contraceptive methods, primary care and family planning and practitioners could consider adopting these interventions. Although our review suggests these interventions are clinically effective, a cost-benefit analysis may be required to evaluate applicability.

Plain-language summary: We did computer searches for relevant studies and looked at the reference lists of study reports to identify more studies. We found nine studies of moderate to low quality. Three studies on contraceptive counselling and referrals by community workers showed an increase in use of the copper IUD. Two studies on antenatal contraceptive counselling and one study on postnatal couple counselling, with provision of an information leaflet before being discharged from the maternity ward, also showed an increase in use of the copper IUD. A study on postnatal home visits and two studies on enhanced postabortion contraceptive counselling did not show an increase in use of the copper IUD. More high-quality research is needed to look at the longer-term effectiveness of interventions to improve use of the copper IUD.
Abstract: We included only one RCT that involved 64 women. We judged this study as being at high risk of bias. Post-operative morbidity and mortality were not addressed, and secondary outcomes of patient cosmetic evaluations and psychosocial well-being post-reconstruction were inadequately reported. Based on limited data there was some, albeit unreliable, evidence that immediate reconstruction compared with delayed or no reconstruction, reduced psychiatric morbidity reported three months post-operatively. The current level of evidence for the effectiveness of immediate versus delayed reconstruction following surgery for breast cancer was based on a single RCT with methodological flaws and a high risk of bias, which does not allow confident decision-making about choice between these surgical options. Until high quality evidence is available, clinicians may wish to consider the recommendations of relevant guidelines and protocols. Although the limitations and ethical constraints of conducting RCTs in this field are recognised, adequately powered controlled trials with a focus on clinical and psychological outcomes are still required. Given the paucity of RCTs in this subject, in future versions of this review we will look at study designs other than RCTs specifically good quality cohort and case-control studies.

Plain-language summary: Several non-randomised studies have reported differences in the psychological benefits, aesthetics and complication rates based on the timing of reconstruction. This review sought to compare the effects of the timing of reconstruction on morbidity and mortality, patient satisfaction and psychosocial well-being. Only one eligible randomised controlled trial (RCT) was found, which involved 64 women. However, because a substantial number of participants in the study chose not to undergo delayed reconstruction, it was not possible to make a fair comparison of the mixed group with those participants who underwent immediate reconstruction. Methodological flaws and a high risk of bias also diminished the quality of evidence found in the RCT. Since we have only identified one RCT in this area, an updated version of this review will evaluate other study designs specifically good quality cohort and case-control studies. Further research should aim to provide reliable evidence for people to make informed decisions as to the best and most appropriate timing of breast reconstruction following surgery for breast cancer.
Abstract: The primary outcomes of this review were clinical features of CVI and its associated symptoms. No new included studies were identified for this update. One prospective cross-over trial was included in this review. It measured the effect of no compression followed by two phases with different gradients of compression stockings on symptoms in 19 female flight attendants who were required to stand, almost continuously, for long periods of time. The included study provided some evidence that compression stockings improved symptoms of leg fatigue in standing workers. However, the strength of the evidence in this review is weak as it is based on only one very small trial which was at high risk of bias. The included study did not address any of the secondary outcomes including quality of life or economic impact of the interventions. Nor did the study report the length of time that the population were required to stand at work. Furthermore, no trials were found which measured the effectiveness of other non-pharmacological interventions or strategies aimed at preventing CVI in standing workers. Due to the extremely limited number of trials, there is insufficient evidence to draw any conclusions about the effectiveness of non-pharmacological interventions for preventing CVI in standing workers. Further large-scale studies examining all possible non-pharmacological interventions and outcomes are required.

Plain-language summary: The trial finding suggested that compression stockings did reduce symptoms associated with CVI including aching of the legs, discomfort, fatigue, swelling and tiredness. However, this evidence was from a very small study. Due to the extremely limited number of trials available, we could not assess the effectiveness of other non-pharmacological interventions in the prevention of this condition. Nor could we ascertain if any intervention had an effect on quality of life or an economic impact such as reducing the number of days of sick leave or work disability. Further research that looks at a broad range of proposed interventions in a clearly defined standing worker population is required.