GEM/cochrane-simplification huggingface dataset:
Abstract: Two studies were included in the review. In the one study in HIV infected women, the IUD was compared with depot progestogen or the oral contraceptive, according to the women's choice. As the majority of women chose depot progestogen, we have included this study in the review, within a mixed hormonal contraception sub-group. Overall, the copper IUD was more effective than depot progestogens/hormonal contraception at preventing pregnancy (risk ratio (RR) 0.47; 95% confidence interval (CI) 0.26 to 0.85). HIV disease progression was reduced in the IUD group (RR 0.66; 95% CI 0.46 to 0.96). There was no significant difference in pelvic inflammatory disease rates between the two groups. Discontinuation of the allocated method was less frequent with the IUD in one study, and less frequent with hormonal contraception in the other study (in which women were allowed to switch between various hormonal methods). In the populations studied, the IUD was more effective than hormonal contraception with respect to pregnancy prevention. High quality research is urgently needed to compare the effects, if any, of these two commonly used contraception methods on HIV acquisition/seroconversion and HIV/AIDS disease progression.

Plain-language summary: We reviewed studies that compared these two highly effective methods and found the IUD to be better at preventing pregnancy than depot medroxyprogesterone acetate (DMPA). Relevant to HIV positive women are the results of one small trial that found that women using the IUD for contraception where less likely to experience a worsening of their HIV disease than those using hormonal contraception. A large, high quality study is urgently needed to shed light on these findings.
Abstract: We found 15 trials from 10 countries; the total number of participants was 2702. Nonsteroidal anti-inflammatory drugs (naproxen, suprofen, mefenamic acid, ibuprofen, indomethacin, flufenamic acid, alclofenac, and diclofenac) were effective in reducing menstrual blood loss associated with IUD use. This held true for women with and without complaints of heavy bleeding. Similarly, these drugs were effective in reducing pain associated with IUD use. In contrast, prophylactic use of nonsteroidal anti-inflammatory drugs had mixed results; studies with ibuprofen found no effect on pain after insertion on IUD discontinuation. No important differences emerged in the one trial comparing the effect of different NSAIDs on bleeding. Nonsteroidal anti-inflammatory drugs reduce bleeding and pain associated with IUD use. NSAIDs should be considered first-line therapy; if NSAIDs are ineffective, tranexamic acid may be considered as second-line therapy. Prophylactic ibuprofen administration with the first six menses after insertion appears unwarranted.

Plain-language summary: We searched for and summarized all the randomized controlled trials that looked at using these drugs to treat bleeding or pain related to an IUD. We also included trials that studied the use of these drugs to prevent these problems. We found 15 trials from 10 countries, with more than 2700 women studied. These drugs reduced both bleeding and pain with intrauterine device use. Whether one drug is better than another was not clear. Similarly, the best dosing was not clear. Preventive treatment with these drugs around the time of IUD insertion had mixed results. No serious problems were reported, but stomach upset and sleepiness can occur with this class of drugs. Because of their safety, low cost, and wide availability, these drugs are appropriate treatment for women who have troublesome bleeding or pain with IUD use.
Abstract: We included 41 fully published studies (2768 patients). Mortality was similar in the N-acetylcysteine group and the placebo group (RR 1.06, 95% CI 0.79 to 1.42; I2 = 0%). Neither did N-acetylcysteine show any significant effect on length of stay, duration of mechanical ventilation or incidence of new organ failure. Early application of N-acetylcysteine to prevent the development of an oxidato-inflammatory response did not affect the outcome, nor did late application that is after 24 hours of developing symptoms. Late application was associated with cardiovascular instability. Overall, this meta-analysis puts doubt on the safety and utility of intravenous N-acetylcysteine as an adjuvant therapy in SIRS and sepsis. At best, N-acetylcysteine is ineffective in reducing mortality and complications in this patient population. At worst, it can be harmful, especially when administered later than 24 hours after the onset of symptoms, by causing cardiovascular depression. Unless future RCTs provide evidence of treatment effect, clinicians should not routinely use intravenous N-acetylcysteine in SIRS or sepsis and academics should not promote its use.

Plain-language summary: N-acetylcysteine is an antioxidant with strong anti-inflammatory effects that is used in treating endotoxaemia and overdoses of acetaminophen. This Cochrane review of 41 randomized controlled trials with 2768 critically ill adult patients found no evidence to support the theory that N-acetylcysteine might reduce the risk of death in adults with SIRS or sepsis. Intravenous N-acetylcysteine did not affect the length of stay in the intensive care unit, duration of mechanical ventilation, duration of support for the cardiovascular system or incidence of new organ failure. There is currently insufficient evidence to support the use of N-acetylcysteine in SIRS or sepsis. We also found that when N-acetylcysteine was administered more than 24 hours after the development of clinical signs of SIRS or sepsis it may even be harmful, by causing cardiovascular depression. Twenty of the trials used N-acetylcysteine in patients around the time of surgery, including cardiac, vascular and major abdominal surgery, and liver transplantation. Eight studies evaluated N-acetylcysteine in patients with severe sepsis or septic shock associated with the medical conditions acute respiratory distress syndrome (ARDS), multiple organ failure, liver failure, malaria or burns. The dosing of N-acetylcysteine, timing and duration of treatment, from a single intravenous dose to infusions up to seven days, varied. Twenty papers had a low risk of bias.
Abstract: We included four trials (552 participants) that compared biphasic and monophasic waveform defibrillation in people with OHCA. Based on the assessment of five quality domains, we identified two trials that were at high risk of bias, one trial at unclear risk of bias and one trial at low risk of bias. The risk ratio (RR) for failure to achieve ROSC after biphasic compared to monophasic waveform defibrillation was 0.86 (95% CI 0.62 to 1.20; four trials, 552 participants). The RR for failure to defibrillate on the first shock following biphasic defibrillation compared to monophasic was 0.84 (95% CI 0.70 to 1.01; three trials, 450 participants); and 0.81 (95% CI 0.61 to 1.09; two trials, 317 participants) for one to three stacked shocks. The RR for failure to achieve ROSC after the first shock was 0.92 (95% CI 0.81 to 1.04; two trials, 285 participants). Biphasic waveforms did not reduce the risk of death before hospital admission (RR 1.05, 95% CI 0.90 to 1.23; three trials, 383 participants) or before hospital discharge (RR 1.05, 95% CI 0.78 to 1.42; four trials, 550 participants). There was no statistically significant heterogeneity in any of the pooled analyses. None of the included trials reported adverse events. It is uncertain whether biphasic defibrillators have an important effect on defibrillation success in people with OHCA. Further large studies are needed to provide adequate statistical power.

Plain-language summary: We searched the literature up to 10 September 2014 and tried to find all available research (published and unpublished) that compared these two types of defibrillators. We only included trials with a high-quality study design to avoid the possibility of inaccurate results. Four trials (552 participants) met the inclusion criteria of our review. Several included trials were potentially at risk of misleading results due to features of their study design. When we combined these trial results, we found that using the newer biphasic waveform defibrillators may be associated with lower failure rates of restarting a person's heart, but these results were imprecise. There was no difference in the number of people who were alive on arrival at the hospital or who were discharged from the hospital alive. No included trials reported on side effects or operator safety. We are uncertain as to whether biphasic defibrillators have an important effect on being able to restart a person's heart because the results were imprecise.
Abstract: Seven studies with 428 participants were included in this review; only two of these had published usable results. Individual patient data were obtained from one trial (Ballard 2002) and additional analyses performed. The additional analyses conducted using individual patient data from Ballard 2002 revealed a statistically significant treatment effect in favour of the aromatherapy intervention on measures of agitation (n = 71, MD -11.1, 95% CI -19.9 to -2.2) and behavioural symptoms (n = 71, MD -15.8, 95% CI -24.4 to -7.2). Burns 2011, however, found no difference in agitation (n = 63, MD 0.00, 95% CI -1.36 to 1.36), behavioural symptoms (n = 63, MD 2.80, 95% CI -5.84 to 11.44), activities of daily living (n = 63, MD -0.50, 95% CI -1.79 to 0.79) and quality of life (n = 63, MD 19.00, 95% CI -23.12 to 61.12). Burns 2011 and Fu 2013 found no difference in adverse effects (n = 124, RR 0.97, 95% CI 0.15 to 6.46) when aromatherapy was compared to placebo. The benefits of aromatherapy for people with dementia are equivocal from the seven trials included in this review. It is important to note there were several methodological difficulties with the included studies. More well-designed, large-scale randomised controlled trials are needed before clear conclusions can be drawn regarding the effectiveness of aromatherapy for dementia. Additionally, several issues need to be addressed, such as whether different aromatherapy interventions are comparable and the possibility that outcomes may vary for different types of dementia.

Plain-language summary: Of the seven randomised controlled trials that we found, only two trials including 186 people had useable data. The analysis of these two small trials showed inconsistent effects of aromatherapy on measures of agitation, behavioural symptoms and quality of life. More large-scale randomised controlled trials are needed before firm conclusions can be reached about the effectiveness of aromatherapy for dementia.
Abstract: We identified one new randomized clinical trial in this update which includes six randomized clinical trials involving 6781 participants in total, five randomized clinical trials in adult (N = 6307) and one randomized clinical trial in paediatric (N = 474) participants. All trials had high risk of bias and were sponsored by the pharmaceutical industry. APC compared with placebo did not significantly affect all-cause mortality at day 28 compared with placebo (856/3643 (23.49%) versus 837/3549 (23.58%); RR 1.00, 95% confidence interval (CI) 0.88 to 1.14; I2 = 49%). APC did not significantly affect in-hospital mortality (393/1767 (22.2%) versus 379/1710 (22.1%); RR 1.01, 95% CI 0.87 to 1.16; I2 = 20%). APC was associated with an increased risk of serious bleeding (113/3424 (3.3%) versus 74/3343 (2.2%); RR 1.45, 95% CI 1.08 to 1.94; I2 = 0%). APC did not significantly affect serious adverse events (463/3334 (13.9%) versus 439/3302 (13.2%); RR 1.04, 95% CI 0.92 to 1.18; I2 = 0%). Trial sequential analyses showed that more trials do not seem to be needed for reliable conclusions regarding these outcomes. This updated review found no evidence suggesting that APC should be used for treating patients with severe sepsis or septic shock. APC seems to be associated with a higher risk of bleeding. The drug company behind APC, Eli Lilly, has announced the discontinuation of all ongoing clinical trials using this drug for treating patients with severe sepsis or septic shock. APC should not be used for sepsis or septic shock outside randomized clinical trials.

Plain-language summary: On 25th October 2011, the European Medicines Agency issued a press release on the worldwide withdrawal of Xigris® (human recombinant activated protein C) from the market by Eli Lilly due to lack of beneficial effect on 28-day mortality in the PROWESS-SHOCK trial. Furthermore, Eli Lily has announced the discontinuation of all ongoing clinical trials. APC should not be used for sepsis or septic shock outside randomized clinical trials. Current evidence does not support the use of human recombinant activated protein C in adults or children with severe sepsis or septic shock; moreover, there is an increased risk of bleeding associated with its use.
Abstract: This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal. Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non-steroidal anti-inflammatory drugs, with the benefit of longer duration of action.

Plain-language summary: This review update assessed evidence from 2641 participants in 20 randomised, double blind, placebo-controlled clinical trials of oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Oral oxycodone 10 mg plus paracetamol 650 mg provided effective analgesia. About half of those treated experienced at least half pain relief over 4 to 6 hours, and the effects lasting up to 10 hours. Higher doses gave more effect. Associated adverse events (predominantly nausea, vomiting, dizziness and somnolence) were more frequent with oxycodone or oxycodone plus paracetamol than with placebo, but studies of this type are of limited use for studying adverse effects. Limited information about oxycodone on its own suggests that it provided analgesia at doses greater than 5 mg, and that addition of paracetamol made it more effective.
Abstract: We included 15 trials, involving 1438 participants. The 2 trials (71 participants) comparing terbinafine and griseofulvin produced a pooled risk ratio (RR) of 2.26 (95% confidence interval (CI) 1.49 to 3.44) in favour of terbinafine's ability to cure infection. No significant difference was detected between terbinafine and itraconazole, fluconazole and itraconazole, fluconazole and ketoconazole, or between griseofulvin and ketoconazole, although the trials were generally small. Two trials showed that terbinafine and itraconazole were effective compared with placebo: terbinafine (31 participants, RR 24.54, 95% CI 1.57 to 384.32) and itraconazole (72 participants, RR 6.67, 95% CI 2.17 to 20.48). All drugs reported adverse effects, with gastrointestinal effects most commonly reported. Ten of the trials were published over 15 years ago, and this is reflected by the poor reporting of information from which to make a clear 'Risk of bias' assessment. Only one trial was at low risk of bias overall. The majority of the remaining trials were judged as 'unclear' risk of bias because of the lack of clear statements with respect to methods of generating the randomisation sequence and allocation concealment. More trials achieved blinding of participants and personnel than blinding of the outcome assessors, which was again poorly reported. The evidence suggests that terbinafine is more effective than griseofulvin, and terbinafine and itraconazole are more effective than no treatment. In order to produce more reliable data, a rigorous evaluation of different drug therapies needs to be undertaken with larger sample sizes to ensure they are large enough to show any real difference when two treatments are being compared. It is also important to continue to follow up and collect data, preferably for six months after the end of the intervention period, to establish whether or not the infection recurred.

Plain-language summary: Athlete's foot (tinea pedis) is a fungal infection of the feet that is easily spread and difficult to get rid of. This review compared different oral antifungal drugs (i.e. drugs taken by mouth), and it included 15 trials, involving 1438 participants. There are several different kinds of oral treatments, and the trials we found considered all the oral drugs used to treat athlete's foot. We found terbinafine and itraconazole to be more effective than placebo. And we found terbinafine to be more effective than griseofulvin. Griseofulvin is a treatment that was developed much earlier than the new treatments, such as terbinafine and itraconazole; these newer treatments tend to be most evaluated. Trials of other drugs were not large enough to show differences between them. All drugs had side-effects; gastrointestinal effects were the most common. In future clinical trials, larger numbers of participants are needed to test different treatments in order to produce more reliable data. Also, future research should consider the costs of the different treatment approaches.
Abstract: Two studies met the inclusion criteria but only one contributed data for the prespecified outcomes. Caffeinated instant coffee (568 women) was compared with decaffeinated instant coffee (629 women) and it was found that reducing the caffeine intake of regular coffee drinkers (3+ cups/day) during the second and third trimester by an average of 182 mg/day did not affect birthweight (g) (mean difference (MD) 20.00, 95% confidence interval (CI) -48.68 to 88.68; one study, 1197 participants; low quality evidence), preterm birth (risk ratio (RR) 0.81, 95% CI 0.48 to 1.37; one study, 1153 participants; low quality evidence) or small-for-gestational age (RR 0.97, 95% 0.57 to 1.64; one study, 1150 participants). Risk of bias was moderate in both studies. Two outcomes were assessed and assigned a quality rating using the GRADE methods. Evidence for these two outcomes (birthweight and preterm birth) was assessed as of low quality, with downgrading decisions due to the relatively small sample sizes and the wide confidence interval of the one included trial that contributed data. Neither of the studies reported on any of the other primary outcomes (low birthweight; first trimester fetal loss; perinatal mortality; fetal hypoxia; fetal tachycardia) or on any of the reviews neonatal or maternal outcomes. There is insufficient evidence to confirm or refute the effectiveness of caffeine avoidance on birthweight or other pregnancy outcomes. There is a need to conduct high-quality, double-blinded RCTs to determine whether caffeine has any effect on pregnancy outcome.

Plain-language summary: Two studies met the inclusion criteria but only one contributed data to the outcomes of interest. The study was based in Denmark. Women less than 20 weeks pregnant were randomly assigned to drinking caffeinated instant coffee (568 women after exclusions) or decaffeinated instant coffee (629 women). Drinking three cups of coffee a day in early pregnancy had no effect on birthweight, preterm births or growth restriction. Both included studies were randomised controlled trials. One randomly allocated pregnant women to either caffeinated or decaffeinated groups. It was unclear from the other whether allocation concealment was undertaken. Blinding of personnel and study participants was satisfactory in both studies while blinding of outcome assessor was not clearly stated. Attrition bias was also not clearly explained in one study. The results from the one trial that provided data for analysis showed that there was no evidence of an effect of caffeine avoidance on the outcomes birthweight, preterm birth or small-for-gestational age. Two outcomes were assessed and assigned a quality rating using the GRADE methods. Evidence for these two outcomes, namely birthweight and frequency of preterm birth, was assessed as of low quality, with downgrading decisions due in part to the relatively small sample sizes and the wide confidence interval of the one included trial that contributed data. There is insufficient evidence to confirm or refute the effectiveness of caffeine avoidance on birthweight or other pregnancy outcomes.
Abstract: Sixteen studies were included (n=3005). Four trials compared the effect of any type (mechanical and/or pharmacological) of prophylaxis versus no prophylaxis. Prophylaxis reduced the risk of DVT in people with trauma (RR 0.52; 95% CI 0.32 to 0.84). Mechanical prophylaxis reduced the risk of DVT (RR = 0.43; 95% CI 0.25 to 0.73). Pharmacological prophylaxis was more effective than mechanical methods at reducing the risk of DVT (RR 0.48; 95% CI 0.25 to 0.95). LMWH appeared to reduce the risk of DVT compared to UH (RR 0.68; 95% CI 0.50 to 0.94). People who received both mechanical and pharmacological prophylaxis had a lower risk of DVT (RR 0.34; 95% CI 0.19 to 0.60) We did not find evidence that thromboprophylaxis reduces mortality or PE in any of the comparisons assessed. However, we found some evidence that thromboprophylaxis prevents DVT. Although the strength of the evidence was not high, taking into account existing information from other related conditions such as surgery, we recommend the use of any DVT prophylactic method for people with severe trauma.

Plain-language summary: Sixteen studies involving 3,005 people are included in this review. We did not find strong evidence that either mechanical or pharmacological interventions reduce death or clots travelling to the lungs, but we found some evidence that they can prevent clots from forming in the legs.