GEM/cochrane-simplification huggingface dataset:
Abstract: Two randomised controlled trials contributed to this literature, enrolling 586 participants, and found no critical difference between TDF and AZT in regards to serious adverse events or virologic response. The trials did find higher rates of adherence and immunologic response in TDF-containing regimens compared with those containing AZT. The quality of the literature to support this conclusion is moderate to high. Drug resistance was more common for TDF than AZT, but the quality of this literature is low, with only one study reporting this outcome. It should be noted that the two studies compared two different drugs in addition to TDF and AZT; one had lamivudine (3TC) and nevirapine (NVP) and the other had emtricitabine (FTC) and efavirenz (EFV). We conclude that for the critical outcomes of virologic response and serious adverse events initial ART regimens containing TDF are equivalent to those containing AZT. However, TDF is superior to AZT in terms of immunologic response and adherence and more frequent emergence of resistance. How much the other drugs in the regimens contributed to these findings is unclear, and true head-to-head trials are still warranted. The role of each drug in initial ART will likely be driven by their specific toxicities.

Plain-language summary: The purpose of this review was to assess which of these two medications was the best for initial treatment for people living with HIV, and through our search we identified two randomised controlled trials. We did not find any critical difference between the two medications in regards to serious adverse events or virologic response, but did find that TDF is superior to AZT in terms of immunologic response and adherence and more frequent emergence of resistance. However, these two studies are not directly comparable because they used two related different drugs in addition to TDF and AZT. Future studies and recommendations should focus on specific toxicities and tolerability when comparing these two medications.
Abstract: We included 16 randomised trials. The number of deaths was 254 in the tacrolimus group (1899 patients) and 302 in the cyclosporin group (1914 patients). At one year, mortality (RR 0.85, 95% CI 0.73 to 0.99) and graft loss (RR 0.73, 95% CI 0.61 to 0.86) were significantly reduced in tacrolimus-treated recipients. Tacrolimus reduced the number of recipients with acute rejection (RR 0.81, 95% CI 0.75 to 0.88), and steroid-resistant rejection (RR 0.54, 95% CI 0.47 to 0.74) in the first year. Differences were not seen with respect to lymphoproliferative disorder or de-novo dialysis rates, but more de-novo insulin-requiring diabetes mellitus (RR 1.38, 95% CI 1.01 to 1.86) occurred in the tacrolimus group. More patients were withdrawn from cyclosporin therapy than from tacrolimus (RR 0.57, 95% CI 0.49 to 0.66). Tacrolimus is superior to cyclosporin in improving survival (patient and graft) and preventing acute rejection after liver transplantation, but it increases the risk of post-transplant diabetes. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid acute rejection and steroid-resistant rejection in nine and seven patients, respectively, and graft loss and death in five and two patients, respectively, but four additional patients would develop diabetes after liver transplantation.

Plain-language summary: This is a review of the clinical trials that compared patients initially prescribed one of the two anti-rejection drugs after liver transplantation. Sixteen trials (3813 participants) were included. The review shows that tacrolimus is marginally better than cyclosporin at preventing patient death and graft loss. Tacrolimus is substantially better than cyclosporin at preventing rejection. No differences were seen between the drugs with respect to adverse events (renal failure, lymphoproliferative disorder) except for diabetes mellitus, which was more common with tacrolimus. After liver transplantation more patients stayed on tacrolimus than on cyclosporin. Tacrolimus is more beneficial than cyclosporine and should be considered the treatment of choice after liver transplantation. This review does not evaluate the benefit or harm of switching from one anti-rejection drug to another.
Abstract: We included 59 studies with a total of 13,342 participants. Compared to no treatment control MI showed a significant effect on substance use which was strongest at post-intervention SMD 0.79, (95% CI 0.48 to 1.09) and weaker at short SMD 0.17 (95% CI 0.09 to 0.26], and medium follow-up SMD 0.15 (95% CI 0.04 to 0.25]). For long follow-up, the effect was not significant SMD 0.06 (95% CI-0.16 to 0.28). There were no significant differences between MI and treatment as usual for either follow-up post-intervention, short and medium follow up. MI did better than assessment and feedback for medium follow-up SMD 0.38 (95% CI 0.10 to 0.66). For short follow-up, there was no significant effect . For other active intervention there were no significant effects for either follow-up. There was not enough data to conclude about effects of MI on the secondary outcomes. MI can reduce the extent of substance abuse compared to no intervention. The evidence is mostly of low quality, so further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Plain-language summary: We searched for studies that had included people with alcohol or drug problems and that had divided them by chance into MI or a control group that either received nothing or some other treatment. We included only studies that had checked video or sound recordings of the therapies in order to be certain that what was given really was MI. The results in this review are based on 59 studies. The results show that people who have received MI have reduced their use of substances more than people who have not received any treatment. However, it seems that other active treatments, treatment as usual and being assessed and receiving feedback can be as effective as motivational interviewing. There was not enough data to conclude about the effects of MI on retention in treatment, readiness to change, or repeat convictions.The quality of the research forces us to be careful about our conclusions, and new research may change them.
Abstract: Two studies met the inclusion criteria. No study looked at our main outcome: dog bite rates. The included studies were randomised controlled trials conducted in kindergarten and primary schools. Their methodology was of moderate quality. One study showed that the intervention group showed less 'inappropriate behaviour' when observed in the presence of a dog after a 30-minute educational intervention. Another study showed an increase in knowledge and in caution after an information programme. There is no direct evidence that educational programmes can reduce dog bite rates in children and adolescents. Educating children who are less than 10 years old in school settings could improve their knowledge, attitude and behaviour towards dogs. Educating children and adolescents in settings other than schools should also be evaluated. There is a need for high quality studies that measure dog bite rates as an outcome. To date, evidence does not suggest that educating children and adolescents is effective as a unique public health strategy to reduce dog bite injuries and their consequences.

Plain-language summary: Two studies were included in this review. Both were of moderate methodological quality and evaluated the effectiveness of educating children on preventing dog bite injuries. Both studies involved a 30-minute lesson. One study additionally compared the effect of educating the children's parents through a leaflet. One study videotaped the way children behaved when exposed to an unknown dog, and their behaviour was observed. The main outcome reported in both studies was a change in behaviour. It is unclear from this review whether educating children can reduce dog bite injuries as dog bite rates were not reported as an outcome in either of the included studies. The effect of educating children and adolescents in settings other than schools has not been evaluated. There is a general lack of evidence about the impact of education to prevent dog bites in children and adolescents, therefore further studies that look at dog bite rates after an intervention are recommended. Education of children and adolescents should not be the only public health strategy to reduce dog bites and their dramatic consequences.
Abstract: We included five completed trials, involving 4197 participants; all tested transdermal glyceryl trinitrate (GTN), an NO donor. The assessed risk of bias was low across the included studies; one study was double-blind, one open-label and three were single-blind. All included studies had blinded outcome assessment. Overall, GTN did not improve the primary outcome of death or dependency at the end of trial (modified Rankin Scale (mRS) > 2, OR 0.97, 95% CI 0.86 to 1.10, 4195 participants, high-quality evidence). GTN did not improve secondary outcomes, including death (OR 0.78, 95% CI 0.40 to 1.50) and quality of life (MD -0.01, 95% CI -0.17 to 0.15) at the end of trial overall (high-quality evidence). Systolic/diastolic blood pressure (BP) was lower in people treated with GTN (MD -7.2 mmHg (95% CI -8.6 to -5.9) and MD -3.3 (95% CI -4.2 to -2.5) respectively) and heart rate was higher (MD 2.0 beats per minute (95% CI 1.1 to 2.9)). Headache was more common in those randomised to GTN (OR 2.37, 95% CI 1.55 to 3.62). We did not find any trials assessing other nitrates, L-arginine, or NOS-I. There is currently insufficient evidence to recommend the use of NO donors, L-arginine or NOS-I in acute stroke, and only one drug (GTN) has been assessed. In people with acute stroke, GTN reduces blood pressure, increases heart rate and headache, but does not alter clinical outcome (all based on high-quality evidence).

Plain-language summary: This review is up-to-date as of September 2016. We included five trials involving 4197 people; all trials assessed glyceryl trinitrate, a drug that is given as a skin patch and which releases nitric oxide. One study was international, whilst the remainder were studies performed at single centres. Not all trials contributed data to all outcomes. We used both unpublished and published information, where available. We did not find any trials assessing other nitrate drugs, L-arginine, or nitric oxide synthase inhibitors. Overall, glyceryl trinitrate did not improve the rate of death or dependency compared with those who did not receive glyceryl trinitrate after acute stroke. Glyceryl trinitrate did not improve other outcomes including death and quality of life. Glyceryl trinitrate lowers blood pressure, and increases heart rate and headache in people with acute stroke. The key results are based on high-quality evidence. There is currently insufficient evidence to recommend the use of drugs affecting nitric oxide production in acute stroke. Overall, glyceryl trinitrate is inexpensive, lowers blood pressure, increases heart rate and headache, but does not change clinical outcomes in people who have suffered a stroke.
Abstract: Two cohort studies and four case control studies met the inclusion criteria for the primary prevention review. The two cohort studies found no effect of exposure to calcium channel blockers on the risk of developing PD. Three case control studies looked at the effects of exposure to calcium channel blockers and beta blockers on the risk of developing PD but the assessment periods of exposure were markedly different prior to PD onset, and different subclasses of drugs were examined, so results were not comparable. A protective effect of centrally acting calcium channel blockers was found in one study. Two trials and one ongoing trial met the inclusion criteria for the secondary prevention review. Each completed trial examined a different class of anti-hypertensive drug. The ongoing trial is examining the effects of the calcium channel blocker isradipine on motor symptoms and disease progression. It follows an earlier tolerability study. The results are due in the year 2012. Adverse effects were noted in all included trials and included intolerability to the drugs and worsening PD symptoms. There is currently a lack of evidence for the use of antihypertensive drugs for either the primary or secondary prevention of PD. More observational studies are required to identify potential drugs to go forward for safety and tolerability studies in people with early PD. The results of the ongoing trial will help inform further research.

Plain-language summary: Epidemiological or observational studies were used to see if taking a blood pressure lowering drug reduces the risk of developing PD in the general population. Only six studies were found. Three studies of the same design looked at the same classes of blood pressure lowering drugs but used different methods so the results could not be combined. Clinical trials were used to see if taking a blood pressure lowering drug when you already have PD reduces symptoms or slows disease progression. Only two completed trials were found, all reporting the effects of different classes of drugs. One trial of a drug belonging to the group called calcium channel blockers is still underway and the results, which are due in 2012, will help inform further studies. Very little information was found for either primary or secondary prevention. More studies are needed to look at different blood pressure lowering drugs and their effects on the risk of developing PD. From these studies, particular potential drugs will be identified to go forward for clinical trials in patients who have PD, to see if they improve symptoms or slow down the disease. It is important that we have more information about the side effects for people with PD who are taking these drugs and that any benefits far outweigh any harms.
Abstract: A total of 15 studies of good methodological quality met the inclusion criteria by randomly assigning 7814 participants with predominantly poorly reversible, severe COPD. Data were most plentiful for the FPS combination. Exacerbation rates were significantly reduced with combination therapies (rate ratio 0.87, 95% CI 0.80 to 0.94, 6 studies, N = 5601) compared with ICS alone. The mean exacerbation rate in the control (ICS) arms of the six included studies was 1.21 exacerbations per participant per year (range 0.88 to 1.60), and we would expect this to be reduced to a rate of 1.05 (95% CI 0.97 to 1.14) among those given combination therapy. Mortality was also lower with the combination (odds ratio (OR) 0.78, 95% CI 0.64 to 0.94, 12 studies, N = 7518) than with ICS alone, but this was heavily weighted by a three-year study of FPS. When this study was removed, no significant mortality difference was noted. The reduction in exacerbations did not translate into significantly reduced rates of hospitalisation due to COPD exacerbation (OR 0.93, 95% CI 0.80 to 1.07, 10 studies, N = 7060). Lung function data favoured combination treatment in the FPS, BDF and MF/F trials, but the improvement was small. Small improvements in health-related quality of life were measured on the St George's Respiratory Questionnaire (SGRQ) with FPS or BDF compared with ICS, but this was well below the minimum clinically important difference. Adverse event profiles were similar between the two treatments arms, and rates of pneumonia when it was diagnosed by chest x-ray (CXR) were lower than those reported in earlier trials. Combination ICS and LABA offer some clinical benefits in COPD compared with ICS alone, especially for reduction in exacerbations. This review does not support the use of ICS alone when LABAs are available. Adverse events were not significantly different between treatments. Further long-term assessments using practical outcomes of current and new 24-hour LABAs will help determine their efficacy and safety. For robust comparisons as to their relative effects, long-term head-to-head comparisons are needed.

Plain-language summary: Our review found 15 studies that compared a combination of ICS/LABA with ICS alone. We found that on the whole, combination inhalers reduced the frequency of flare-ups (not including hospitalisations) compared with ICS alone. The studies showed that on average, the number of exacerbations per participant was reduced, as was the probability of death, during treatment. Quality of life and lung function showed improvement with combination treatment compared with ICS, but no difference between them was noted in terms of adverse effects, or the likelihood of having no flare-ups at all. Future research should assess the efficacy of BDF and MF/F because most evidence gathered to date, including for mortality, has been drawn from FPS studies.
Abstract: Three trials were included, all of which evaluated doxycyline use. Trial quality suffered from a lack of intention-to-treat analysis and variability across trials in methodology and targeted outcomes. One trial assessed post-exposure prophylaxis in an indigenous population after a flood without apparent efficacy in reduction of clinical or laboratory identified Leptospira infection. Two trials assessed pre-exposure prophylaxis, one among deployed soldiers and another in an indigenous population. Despite an odds ratio of 0.05 (95% CI 0.01 to 0.36) for laboratory-identified infection among deployed soldiers on doxycyline in one of these two trials, pooled data showed no statistically significant reduction in Leptospira infection among participants (Odds ratio 0.28 (95% CI 0.01 to 7.48). Minor adverse events (predominantly nausea and vomiting) were more common among those on doxycycline with an odds ratio of 11 (95% CI 2.1 to 60). Regular use of weekly oral doxycycline 200 mg increases the odds for nausea and vomiting with unclear benefit in reducing Leptospira seroconversion or clinical consequences of infection.

Plain-language summary: This is a systematic review of clinical research testing whether taking the antibiotic can prevent infection from a water-borne bacteria called Leptospira. Data from different trials had conflicting results, and these trials targeted different kinds of people - travellers and people who live in at risk areas, encompassing soldiers, farmers, and students. Taken together, the data does not support the practice in all cases, though short term travellers with a potential for high risk exposure may be helped. People who took doxycycline were more likely to have stomach pain, nausea, and vomiting but the medication had to be stopped in only a few participants.
Abstract: Thirteen randomised clinical trials assessed milk thistle in 915 patients with alcoholic and/or hepatitis B or C virus liver diseases. The methodological quality was low: only 23% of the trials reported adequate allocation concealment and only 46% were considered adequately double-blinded. Milk thistle versus placebo or no intervention had no significant effect on mortality (RR 0.78, 95% CI 0.53 to 1.15), complications of liver disease (RR 0.95, 95% CI 0.83 to 1.09), or liver histology. Liver-related mortality was significantly reduced by milk thistle in all trials (RR 0.50, 95% CI 0.29 to 0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28 to 1.19). Milk thistle was not associated with a significantly increased risk of adverse events (RR 0.83, 95% CI 0.46 to 1.50). Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed.

Plain-language summary: Several trials have studied the effects of milk thistle for patients with liver diseases. This systematic review could not demonstrate significant effects of milk thistle on mortality or complications of liver diseases in patients with alcoholic and/or hepatitis B or C liver diseases combining all trials or high-quality trials. Low-quality trials suggested beneficial effects. High-quality randomised clinical trials on milk thistle versus placebo are needed.
Abstract: Only one RCT, providing very low-quality evidence, was identified and included. Thirteen patients received HBO therapy while another 13 did not. Two to six implants were placed in people with fully edentulous mandibles to be rehabilitated with bar-retained overdentures. One year after implant loading, four patients had died from each group. One patient, treated with HBO, developed an osteoradionecrosis and lost all implants so the prosthesis could not be provided. Five patients in the HBO group had at least one implant failure versus two in the control group. There were no statistically significant differences for prosthesis and implant failures, postoperative complications and patient satisfaction between the two groups. Despite the limited amount of clinical research available, it appears that HBO therapy in irradiated patients requiring dental implants may not offer any appreciable clinical benefits. There is a definite need for more RCTs to ascertain the effectiveness of HBO in irradiated patients requiring dental implants. These trials ought to be of a high quality and reported as recommended by the CONSORT statement (www.consort-statement.org/). Each clinical centre may have limited numbers of patients and it is likely that trials will need to be multicentred.

Plain-language summary: The evidence on which this review is based was up-to-date as of 1 July 2013. One small study carried out at a head and neck cancer clinic based at a university in the Netherlands was found. The study included 26 adults who had been treated for head and neck cancer either with radiotherapy or a combination of radiotherapy and surgery. All participants were missing all their teeth in the lower jaw and were experienced problems retaining a denture. The participants were split into two groups, 13 of them were treated with HBO and the other 13 were not. Only one small trial that was at high risk of bias compared treatment with HBO with treatment without HBO. The results failed to determine a benefit for HBO therapy in preventing failure of dental implants or other serious complications such as the death of bone in the jaw caused by radiotherapy treatment. More reliable studies are needed to provide the final answer to this question. The quality of evidence was very low as it was based on one small trial at high risk of bias.