GEM/cochrane-simplification huggingface dataset:
Abstract: Three RCTs, involving 192 participants, met inclusion criteria for this review. No significant differences for overall survival (OS) were reported in any of the trials: in the first trial, 33 patients received whole brain radiation therapy and no significant difference was found between patients treated with topotecan and those not treated with topotecan. In a second trial, in which 120 patients were randomized to receive teniposide with or without brain radiation therapy, the authors reported that the median progression-free survival (brain-specific progression-free survival (PFS)) was 3.5 months in the combined modality arm and 3.2 in the teniposide alone arm. In a third trial, comparing sequential and concomitant chemoradiotherapy (teniposide plus cisplatin) in 39 participants, the survival difference between the two groups was not statistically significant. While the first trial reported no significant difference in PFS, the second RCT found a significant difference favoring combined therapy group. The second trial also found that patients receiving chemoradiotherapy (teniposide plus whole brain radiotherapy) had a higher complete response rate than those receiving only the topoisomerase inhibitor. Given the paucity of robust studies assessing the clinical effects of treatments, available evidence is insufficient to judge the effectiveness and safety of chemotherapy for the treatment of BM from SCLC. Published studies are insufficient to address the objectives of this review. According to the available evidence included in this review, chemotherapy does not improve specific brain PFS and OS in patients with SCLC. The combined treatment of teniposide and brain radiation therapy contributed to outcome in terms of increased complete remission and shorter time to progression (though not OS).

Plain-language summary: After an extensive review of medical literature we identified three trials assessing different treatment strategies for patients with BM from SCLC. Only one of the studies compared chemotherapy (topotecan) versus no chemotherapy, but in patients treated with whole brain radiotherapy. Another study randomized patients to receive teniposide with or without brain radiation therapy, and the third one, compared sequential and concomitant chemoradiotherapy (teniposide plus cisplatin). Studies show that people who received chemotherapy did not live longer or have a longer time before the BM grew again compared to those who were treated with brain radiation therapy alone. Hematological toxicities occurred more often in patients exposed to chemoradiotherapy in one study and in patients receiving sequential treatment in another study. A major limitation of this review was the low number of included studies and participants.
Abstract: Four RCTs that included 365 participants after one year of treatment were included. Only one trial reported final height in 61 treated women to be 148 cm and 141 cm in 43 untreated women (mean difference (MD) seven cm, 95% CI 6 to 8). Short-term growth velocity was greater in treated than untreated girls after one year (two trials, MD three cm per year, 95% CI 2 to 4) and after two years (one trial, MD two cm per year, 95% CI 1 to 2.3). Skeletal maturity was not accelerated by treatment with recombinant growth hormone (hGH). Adverse effects were minimally reported. Recombinant human growth hormone (hGH) doses between 0.3 to 0.375 mg/kg/wk increase short-term growth in girls with Turner syndrome by approximately three (two) cm in the first (second) year of treatment. Treatment in one trial increased final height by approximately six cm over an untreated control group. Despite this increase, the final height of treated women was still outside the normal range. Additional trials of the effects of hGH carried out with control groups until final height is achieved would allow better informed decisions about whether the benefits of hGH treatment outweigh the requirement of treatment over several years at considerable cost.

Plain-language summary: The review found some evidence that hGH does increase short-term growth in girls with TS and adult height (an increase of perhaps five centimeters or two inches). However, girls treated with hGH are still substantially shorter than other women as adults. Final height in 61 treated women was 148 cm and 141 cm in 43 untreated women.
Abstract: The search identified 25 studies for consideration but only 10 studies met the inclusion criteria. These included a total of 1015 participants. Generally the studies were poorly designed and underpowered, with low numbers of participants and short durations. Only two studies used our predetermined primary outcome measure (survival at 12 months treatment). However, sufficient data were available from four studies to allow meta-analysis.  In the individual studies, no significant effect was observed for vitamin E 500 mg twice daily; vitamin E 1 g five times daily; acetylcysteine 50 mg/kg daily by subcutaneous infusion; a combination of L-methionine 2 g, vitamin E 400 international units, and selenium (Alsemet) 0.03 mg three times daily; or coenzyme Q10 1800 mg/day and 2700 mg/day. No significant effect was observed on the primary outcome measure in a meta-analysis of all antioxidants combined. No significant differences were demonstrated in any of the secondary outcome measures. The antioxidants were generally well tolerated, without serious side effects. There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect but this was not supported in our analysis. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trials. The high tolerance and safety, and relatively low cost of vitamins C and E, explain the continuing use of these vitamins by physicians and people with amyotrophic lateral sclerosis. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Plain-language summary: In this updated review, we identified 10 studies involving a total of 1015 participants. We did not find any well-designed randomized controlled trial evidence to support the use of these medications. Trials of antioxidants identified in this review were generally of poor methodological quality and lacked statistical power. However, antioxidants are generally well tolerated without serious adverse effects.
Abstract: 73 outreach interventions were identified covering many specialties, countries and settings. Nine studies met the inclusion criteria. Most comparative studies came from urban non-disadvantaged populations in developed countries. Simple 'shifted outpatients' styles of specialist outreach were shown to improve access, but there was no evidence of impact on health outcomes. Specialist outreach as part of more complex multifaceted interventions involving collaboration with primary care, education or other services wasassociated with improved health outcomes, more efficient and guideline-consistent care, and less use of inpatient services. The additional costs of outreach may be balanced by improved health outcomes. This review supports the hypothesis that specialist outreach can improve access, outcomes and service use, especially when delivered as part of a multifaceted intervention. The benefits of simple outreach models in urban non-disadvantaged settings seem small. There is a need for good comparative studies of outreach in rural and disadvantaged settings where outreach may confer most benefit to access and health outcomes.

Plain-language summary: This review examines the benefits and costs of outreach in a range of specialties and in a variety of settings. Simple 'shifted outpatients' styles of specialist outreach were shown to improve access, but there was no evidence of their impact on health outcomes. Outreach as part of more complex multifaceted interventions involving primary care collaborations, education and other services was associated with improved health outcomes, more efficient and guideline-consistent care, and less use of inpatient services. There is a need for better quality evidence evaluating specialist outreach in all settings, but especially in rural and disadvantaged populations.
Abstract: Six trials and 146 patients were included. The proportion improved was significantly better in the group on ketanserin with a Peto's odds ratio (OR) of 2.74 (95% CI 1.42, 5.11) (Cadranel 1986; Dormandy 1988; Kirch 1987; Lukac 1985; van de Wal 1987). When comparing ketanserin to placebo, the decrease in frequency of RP attacks favoured placebo and was statistically significant [WMD (fixed) 25.20 (95% CI 22.55,27.85)] (Kirch 1987). Side effects were significantly more common in the group using active treatment [Peto's OR 2.63 (95% CI 1.42, 4.88)] (Cadranel 1986; Kirch 1987; Lukac 1985; Ortonne 1989; van de Wal 1987). Duration of attacks significantly favoured the placebo group over the active treatment [WMD (fixed) 4.10 (95% CI 3.57, 4.63)] (Kirch 1987). Ketanserin may have some efficacy in the treatment of Raynaud's phenomenon secondary to scleroderma. Overall, ketanserin is not significantly different from placebo for the treatment of Raynaud's phenomenon except for some decrease in the duration of attacks and more subjects improved on ketanserin compared to placebo. However, there were more side effects, and the frequency of attacks actually favored placebo. It can be concluded that ketanserin treatment in Raynaud's phenomenon secondary to scleroderma is not clinically beneficial.

Plain-language summary: Six trials which investigated the effect of ketanserin on 146 patients with either primary Raynaud's phenomenon or Raynaud's phenomenon secondary to systemic sclerosis were included (Cadranel 1986; Dormandy 1988; Kirch 1987; Lukac 1985; Ortonne 1989; van de Wal 1987). Patients treated with ketanserin experienced a greater improvement in mean functional index scores and more patients improved than those treated with placebo, however they also experienced more side effects and an increase in the frequency and duration of attacks. This review assessed a limited number of studies and therefore the conclusions reached need to be investigated further.
Abstract: We included thirty trials, all conducted in high income countries, involving 4691 participants. Median sample size per group was 21. We examined the quality of each trial against eight standard criteria, and all trials were inadequate in relation to three or more of these standards. Trials evaluated contracts in addiction (10 trials), hypertension (4 trials), weight control (3 trials) and a variety of other areas (13 trials). Fifteen trials reported at least one outcome that showed statistically significant differences favouring the contracts group, six trials reported at least one outcome that showed differences favouring the control group and 26 trials reported at least one outcome without differences between groups. Effects on adherence were not detected when measured over longer periods. There is limited evidence that contracts can potentially contribute to improving adherence, but there is insufficient evidence from large, good quality studies to routinely recommend contracts for improving adherence to treatment or preventive health regimens.

Plain-language summary: We found 30 trials involving 4691 participants, examining several types of contracts. The main health problems targeted were substance addictions, hypertension and overweight. Many of the trials were of poor quality and involved small numbers of people. Most were conducted in the USA. In 15 of the trials there was at least one outcome showing statistically significant differences in favour of the contracts group (although some of the improvements in adherence did not remain when measured after a longer period). In six trials at least one outcome showed such differences in favour of the control group. In 26 trials there was at least one outcome for which there was no difference between the contract and control groups. There is not enough reliable evidence available to recommend the routine use of contracts in health services to improve patients' adherence to healthcare activities or other outcomes.
Abstract: We included 21 randomised trials (involving 2222 women) and the majority of them had unclear or high risk of bias. There were several different herbal preparations used within the included trials. The average treatment duration was three to six months. The primary outcome of uterine fibroid related symptoms was not reported in any of the included trials. The majority of the trials reported fibroid volume and size of the uterus. Compared with mifepristone, Tripterygium wilfordii extract was associated with a greater reduction in the fibroid volume (MD -23.03 cm3, 95% CI -28.39 to -17.67; 2 trials) and in uterine size (MD -51.25 cm3, 95% CI -77.70 to -24.80; 2 trials). There was no evidence of a significant difference between Nona Roguy herbal product and gonadotropin-releasing hormone (GnRH) agonist on the average fibroid volume or the uterine size. The combination of Guizhi Fuling formula and mifepristone was associated with a greater reduction in the fibroid volume (-1.72 [-2.42, -1.02] 7 trials) and in uterine size (MD -31.63 [95% CI -54.58, -8.68] 3 trials)) compared with mifepristone alone. Only 13/21 trials reported on adverse events and no serious adverse effects from herbal preparations were reported. Current evidence does not support or refute the use of herbal preparations for treatment of uterine fibroids due to insufficient studies with large sample sizes and of high quality. Further high quality trials evaluating clinically relevant outcomes are warranted.

Plain-language summary: Herbal preparations are commonly used alternatives to drug treatment, surgery, or both. This systematic review included 21 randomised clinical trials involving 2222 women with uterine fibroids. There is no evidence on the effectiveness of herbal preparations for symptom relief as no trials evaluated this properly. Compared with conventional medication, one herbal preparation, Tripterygium wilfordii, may have a more beneficial effect in reducing the volume of uterine fibroids. Another five herbal medicines appeared to be similar to conventional medication in reducing the volume of fibroids. The herbal medicine Guizhi Fuling formula showed a significantly greater effect in reducing the volume of the fibroids when combined with mifepristone versus mifepristone alone. However, these clinical trials were small in terms of the number of participants and the trial quality was low. Thirteen out of 21 included trials reported on adverse effects of herbal preparations and found some minor problems such as stomach discomfort, nausea, hot flushes, and poor appetite although no serious adverse effects were identified. The effect of herbal preparations for uterine fibroids is therefore not confirmed in this review and needs to be studied in large, good quality trials.
Abstract: Six trials met the inclusion criteria. We have not found any new studies since the initial review. In the trial comparing the desogestrel versus levonorgestrel progestin-only pill, desogestrel was not associated with a significantly lower risk of accidental pregnancy; the rate ratio was 0.27 (95% CI 0.06 to 1.19). However, the desogestrel progestin-only pill caused more bleeding problems, although this difference was not statistically significant. The trial comparing low-dose mifepristone versus a levonorgestrel progestin-only pill found similar pregnancy rates. In the trial comparing ethynodiol diacetate versus a combined oral contraceptive, irregular cycles occurred in all women assigned to the progestin-only pill (odds ratio 135.96; 95% CI 7.61 to 2421.02). In a trial comparing two progestin-only and two combined oral contraceptives, the progestin-only pill containing levonorgestrel 30 μg had higher efficacy than did the pill containing norethisterone 350 μg. An early trial found megestrol acetate inferior to other progestin-only pills in terms of efficacy. A study of the timing of pill initiation after birth found no important differences, but high losses to follow up undermined the trial. Evidence is insufficient to compare progestin-only pills to each other or to combined oral contraceptives.

Plain-language summary: We found six trials for the initial review. We have not found any more studies since then. Some studies are several decades old and not very relevant to pills available today. A newer pill containing the progestin desogestrel may work better to prevent pregnancy than an older pill with levonorgestrel. The newer pill caused more bleeding problems. Pills with levonorgestrel may be more effective than pills with other progestins that are no longer used. These studies are not adequate to tell how progestin-only pills compare to each other or to combined (two-hormone) pills. Larger studies with currently used pills are needed to answer these questions.
Abstract: We included 38 studies (15,903 participants) in this review, 18 of which were cluster-randomised trials (11,995 participants) and two were quasi-randomised trials (399 participants). We included 33 studies in the meta-analyses. We included eight studies (3405 participants) in the meta-analysis assessing episodes of relationship violence. There was substantial heterogeneity (I2 = 57%) for this outcome. The risk ratio was 0.77 (95% confidence interval (CI) 0.53 to 1.13). We included 22 studies (5256 participants) in the meta-analysis assessing attitudes towards relationship violence. The standardised mean difference (SMD) was 0.06 (95% CI -0.01 to 0.15). We included four studies (887 participants) in the meta-analysis assessing behaviour related to relationship violence; the SMD was -0.07 (95% CI -0.31 to 0.16). We included 10 studies (6206 participants) in the meta-analysis assessing knowledge related to relationship violence; the results showed an increase in knowledge in favour of the intervention (SMD 0.44, 95% CI 0.28 to 0.60) but there was substantial heterogeneity (I2 = 52%). We included seven studies (1369 participants) in the meta-analysis assessing skills related to relationship violence. The SMD was 0.03 (95% CI -0.11 to 0.17). None of the included studies assessed physical health, psychosocial health or adverse outcomes. Subgroup analyses showed no statistically significant differences by intervention setting or type of participants. The quality of evidence for all outcomes included in our meta-analysis was moderate due to an unclear risk of selection and detection bias and a high risk of performance bias in most studies. Studies included in this review showed no evidence of effectiveness of interventions on episodes of relationship violence or on attitudes, behaviours and skills related to relationship violence. We found a small increase in knowledge but there was evidence of substantial heterogeneity among studies. Further studies with longer-term follow-up are required, and study authors should use standardised and validated measurement instruments to maximise comparability of results.

Plain-language summary: This review looked at the results of 38 studies. The results showed no convincing evidence that the programmes decreased relationship violence, or that they improved participants' attitudes, behaviours and skills related to relationship violence. The results showed that participants' knowledge about relationships improved slightly following the programmes. These results should be interpreted with caution, as individual studies differed in the types of participants and interventions that they used and the ways in which changes were measured. None of the studies looked at the effect of the programmes on physical and mental health. Further studies, which follow participants for a longer period of time and which look at the relationship between attitudes, knowledge, behaviour, skills and the number of times relationship violence occurs, are required to improve our understanding of how well these programmes work.
Abstract: The one study included in this review is a small (n=30) randomised controlled trial lasting 24 weeks. It was followed-up by an open label study with a crossover design. No significant differences were found on any four validated outcomes including global functioning and three measures of cognitive abilities and behavioural problems. 6 out of 16 carers (37%) of participants on donepezil and 2 out of 15 (13%) on placebo reported improvement. No data were available for day to day skills, institutionalisation, reduction in carers' stress or economic outcomes. Half the intervention group and 20% of the placebo group reported adverse events; two participants left because of adverse events. To date there is only one small randomised controlled study on the effect of donepezil. This shows, at best, a modest, non statistically significant trend in favour of people with Down syndrome and Alzheimer's dementia who are able to tolerate donepezil (this drug is currently only dispensed in relatively large doses and is contraindicated for those with cardiac and respiratory problems).This study does not provide good evidence on which to base practice. Findings in an open-label follow up to this study suggest possible benefit in some individuals. Further, larger randomised controlled studies with longer-term follow up are required.

Plain-language summary: This review identified one randomised controlled trial of donepezil in people with Down syndrome. This shows, at best, a modest, non statistically significant trend in favour of people with Down syndrome and Alzheimer's dementia who are able to tolerate donepezil. The trial was of good quality, but small. It is important to note that people with Down syndrome may often have other conditions which mean that the drug is not suitable for all. Further research is needed.
Abstract: Updating the previous review through December 2009 identified 41 additional papers, for a grand total of 278 references. Two-hundred and fourty-two of them were excluded because they analyzed survival (n=27), were repetitive (n=29), letters/reviews (n=71) or had no data (n=115). Thirty-six studies on 12,127 patients remained included: 23 showed a detrimental effect of PBT; 22 used multivariable analyses, and 14 found an independent PBT effect. Pooled estimates of PBT effect on recurrence in randomised studies yielded an OR of 1.42 (95% CI, 1.20 to 1.67) against transfused patients. Stratified meta-analyses confirmed these findings also by site and stage of disease, regardless of timing, type, and in a dose-related fashion, although heterogeneity was detected. Data on surgical techniques was not available for further analysis. This updated meta-analysis confirms the previous findings and supports the association of PBT on the recurrence of curable colorectal cancers. However, since heterogeneity was detected and the effect of surgical technique could not be assessed, a causal relationship cannot still be claimed. Carefully restricted indications for PBT seems necessary.

Plain-language summary: This review include 36 studies, identified from 278 references retrieved until December 2009, and report a moderate association between colorectal cancer recurrence and perioperative transfusions, with an OR of 1.42 (95% CI, 1.20 to 1.67). Similar estimates are present in several subgroup meta-analyses, as well as in meta-analyses stratified for known risk factors. These findings support carefully restricted indications for perioperative blood transfusions in colorectal cancer patients operated for cure, and continue to await the results of studies addressing the role of surgeon-related risk factors on the need for transfusion and disease recurrence.