GEM/cochrane-simplification huggingface dataset:
Abstract: Nine trials in which a total of 754 very preterm or very low birth weight infants participated were eligible for inclusion. Few participants were extremely preterm (< 28 weeks) or extremely low birth weight (< 1000 grams) or growth restricted. These trials did not provide any evidence that early trophic feeding affected feed tolerance or growth rates. Meta-analysis did not detect a statistically significant effect on the incidence of necrotising enterocolitis: typical risk ratio 1.07 (95% confidence interval 0.67 to 1.70); risk difference 0.01 (-0.03 to 0.05). The available trial data do not provide evidence of important beneficial or harmful effects of early trophic feeding for very preterm or very low birth weight infants. The applicability of these findings to extremely preterm, extremely low birth weight or growth restricted infants is limited. Further randomised controlled trials would be needed to determine how trophic feeding compared with enteral fasting affects important outcomes in this population.

Plain-language summary: Analysis of nine trials does not suggest that this practice increases the risk of a severe bowel disorder called 'necrotising enterocolitis'. Further trials could provide more robust evidence to inform this key area of care.
Abstract: Seven trials with a total of 2144 participants were included. Four studies (1959 participants) addressed subjective change in severity of rhinorrhoea. All studies were consistent in reporting statistically significant changes in favour of IB. Nasal congestion was reported in four studies and was found to have no significant change between the two groups. Two studies found a positive response in the IB group for the global assessment of overall improvement. Side effects were more frequent in the IB group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly encountered side effects included nasal dryness, blood tinged mucus and epistaxis. The overall risk of bias in the included studies was moderate. For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well tolerated and self limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms.

Plain-language summary: We identified seven trials that included 2144 participants. There were more side effects with IB, such as dryness of the nose, mucus with streaks of blood and bleeding from the nose. Limitations in this review included two studies with missing participants and four studies with unclear blinding of the participants, personnel or outcome assessors. These limitations resulted in the majority of studies having an unclear risk of bias, which raises the concern of overestimation of the overall effect of IB. We concluded from this review that IB may be effective in improving the runny nose with some side effects that are well tolerated. There is a need for more high-quality studies to determine the effectiveness of IB in relieving common cold symptoms.
Abstract: Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus 60 mg codeine, 3.9 (2.9 to 4.5) for 600 to 650 mg paracetamol plus 60 mg codeine, and 6.9 (4.8 to 12) for 300 mg paracetamol plus 30 mg codeine. Time to use of rescue medication was over four hours with paracetamol plus codeine and two hours with placebo. The NNT to prevent remedication was 5.6 (4.0 to 9.0) for 600 mg paracetamol plus 60 mg codeine over four to six hours. Adverse events increased of mainly mild to moderate severity with paracetamol plus codeine than placebo. Fourteen studies, with 926 participants, were included in the comparison of paracetamol plus codeine with the same dose of paracetamol alone. Addition of codeine increased proportion of participants achieving at least 50% pain relief over four-to-six hours by 10 to 15%, increased time to use of rescue medication by about one hour, and reduced proportion of participants needing rescue medication by about 15% (NNT to prevent remedication 6.9 (4.2 to 19). Adverse events were mainly mild to moderate in severity and incidence did not differ between groups. This update confirms previous findings that combining paracetamol with codeine provided clinically useful levels of pain relief in about 50% of patients with moderate to severe postoperative pain, compared with under 20% with placebo. New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone. At higher doses, more participants experienced adequate pain relief, but the amount of information available for the 1000 mg paracetamol plus 60 mg codeine dose was small, and based on limited information.

Plain-language summary: This review assessed data from twenty-six studies comparing paracetamol plus codeine with placebo, and fourteen studies comparing paracetamol plus codeine with the same dose of paracetamol alone. The combination provided effective pain relief for about 40% of participants experiencing moderate to severe pain after an operation with 600 to 650 mg paracetamol plus 60 mg codeine, the dose most commonly used in these studies, and about 50% of participants with 800 to 1000 mg paracetamol plus 60 mg codeine, the dose most commonly used in clinical practice. The addition of codeine provided effective pain relief to about 10% more participants than the same dose of paracetamol alone. These single dose studies did not associate paracetamol plus codeine with any serious side effects.
Abstract: Twenty studies (986 participants; 966 MS participants and 20 healthy controls) fulfilled the inclusion criteria. The mean age of the participants was 44.6 years, mean length of education was 12.3 years and 70% of the participants were women. Most of the participants had a relapsing-remitting course of disease. The mean Expanded Disability Status Scale score was 3.2 and the mean duration of disease was 14.0 years. On the basis of these studies, we found low-level evidence that neuropsychological rehabilitation reduces cognitive symptoms in MS. Cognitive training was found to improve memory span (standardised mean difference (SMD) 0.54, 95% confidence interval (CI) 0.20 to 0.88, P = 0.002) and working memory (SMD 0.33, 95% CI 0.09 to 0.57, P = 0.006). Cognitive training combined with other neuropsychological rehabilitation methods was found to improve attention (SMD 0.15, 95% CI 0.01 to 0.28, P = 0.03), immediate verbal memory (SMD 0.31, 95% CI 0.08 to 0.54, P = 0.008) and delayed memory (SMD 0.22, 95% CI 0.02 to 0.42, P = 0.03). There was no evidence of an effect of neuropsychological rehabilitation on emotional functions. The overall quality, as well as the comparability of the included studies, was relatively low due to methodological limitations and heterogeneity of interventions and outcome measures. Although most of the pooled results in the meta-analyses yielded no significant findings, 18 of the 20 studies showed some evidence of positive effects when the studies were individually analysed. This review found low-level evidence for positive effects of neuropsychological rehabilitation in MS. The interventions and outcome measures included in the review were heterogeneous, which limited the comparability of the studies. New trials may therefore change the strength and direction of the evidence.

Plain-language summary: Twenty relevant studies comprising a total of 986 participants (966 MS participants and 20 healthy controls) were identified and included in this review. Low-level evidence was found that neuropsychological rehabilitation reduces cognitive symptoms in MS. However, when analysed individually, 18 out of the 20 studies showed positive effects. Cognitive training was found to improve memory span and working memory. Cognitive training combined with other neuropsychological rehabilitation methods was found to improve attention, immediate verbal memory and delayed memory. It is worth noting that the small numbers of patients in the studies and some methodological weaknesses reduce the level of the evidence. To further strengthen the evidence well-designed, high-quality studies are needed.
Abstract: Five randomised or quasi-randomised double-blind trials fulfilled the selection criteria, but were not sufficiently comparable to undertake a meta-analysis. The drugs studied were verapamil (8 participants), diltiazem (56 participants), nifedipine (105 participants) and flunarizine (27 participants). There were limitations in the description of blinding and randomisation, and definition of outcome measures. One trial, using verapamil, showed a difference between groups in muscle force measured by ergometry, but also revealed cardiac side effects. The numbers of people included in the trials were low, and so the studies may not have included enough people for sufficient power to detect small differences in muscle force or function between placebo and control groups. In addition, calcium antagonists were in an early stage of development and some of the second generation drugs that have a better side effect profile, such as amlodipine, have not been studied. There is no evidence to show a significant beneficial effect of calcium antagonists on muscle function in DMD.

Plain-language summary: This is an updated review. In the original review original eight studies were identified and five were high enough quality to be included. In this update no new trials were identified and so five were still included in the review. These studies were of different types of calcium channel blocking drugs and measured a variety of outcomes such as muscle strength, scales of muscle function, biochemical changes in muscle and electrocardiographic findings. Only one study showed a beneficial effect, which was an increase in muscle strength, but in this study the drug used was also associated with cardiac side effects. Adverse effects noted were mostly known side effects of calcium channel blockers.  Limitations of the review were that a meta-analysis could not be done as the trials used different calcium channel blockers and measured different outcomes, and all but one of the trials included a low number of patients. In conclusion, the review did not find calcium antagonists to have a useful effect.
Abstract: Six RCTs with 456 participants and variable treatment and follow-up periods were included. From the limited data, the live birth rate per couple randomly assigned (27% vs 0%; Peto odds ratio (OR) 9.31, 95% confidence interval (CI) 1.17 to 73.75, one study, 30 participants, very low-quality evidence) and the spontaneous pregnancy rate per couple randomly assigned (16% vs 7%; Peto OR 4.94, 95% CI 2.13 to 11.44, five studies, 412 participants, I2 = 0%, moderate-quality evidence) were significantly higher in men receiving gonadotrophin treatment than in men receiving placebo or no treatment. No significant difference between groups was noted when intracytoplasmic sperm injection (ICSI) or intrauterine insemination (IUI) was performed. None of the included studies reported miscarriage rates, and adverse events data were sparse. Encouraging preliminary data suggest a beneficial effect on live birth and pregnancy of gonadotrophin treatment for men with idiopathic male factor subfertility, but because the numbers of trials and participants are small, evidence is insufficient to allow final conclusions. Large multi-centre trials with adequate numbers of participants are needed.

Plain-language summary: There was a trend towards an increase in live birth and pregnancy rates during and within three months of gonadotrophin treatment. The quality of the evidence was very low. We did not find enough studies to allow final conclusions about the use of gonadotrophins in the treatment of men with idiopathic male factor subfertility. The quality of the evidence was very low. More studies on this subject are needed. The evidence is current to January 2013.
Abstract: One trial (46 participants) was eligible for inclusion. After randomization eight participants were withdrawn, mainly because they declined to participate in the trial. Data were analysed for 38 participants at the end of the trial. After a mean follow-up of three years, hip core decompression and physical therapy did not show clinical improvement when compared with physical therapy alone using the score from the original trial (an improvement of 18.1 points for those treated with intervention therapy versus an improvement of 15.7 points with control therapy). We are very uncertain whether there is any difference between groups regarding major complications (hip pain, risk ratio 0.95 (95% confidence interval 0.56 to 1.60; vaso-occlusive crises, risk ratio 1.14 (95% confidence interval 0.72 to 1.80; very low quality of evidence); and acute chest syndrome, risk ratio 1.06 (95% confidence interval 0.44 to 2.56; very low quality of evidence)). This trial did not report results on mortality or quality of life. We found no evidence that adding hip core decompression to physical therapy achieves clinical improvement in people with sickle cell disease with avascular necrosis of bone compared to physical therapy alone. However, we highlight that our conclusion is based on one trial with high attrition rates. Further randomized controlled trials are necessary to evaluate the role of hip-core depression for this clinical condition. Endpoints should focus on participants' subjective experience (e.g. quality of life and pain) as well as more objective 'time-to-event' measures (e.g. mortality, survival, hip longevity). The availability of participants to allow adequate trial power will be a key consideration for endpoint choice.

Plain-language summary: We found one eligible trial, published in 2006, which analysed data from 38 people from 32 different treatment centers from the USA. The trial compared a treatment of surgery and physical therapy with physical therapy on its own. This trial did not show that the addition of surgery to a physical therapy regimen could improve the outcome for people with sickle cell disease and avascular necrosis. After a mean follow-up of three years, the combination of surgery and physical therapies did not show clinical improvement when compared with physical therapy alone. Given that the results are imprecise, we are uncertain as to whether surgery and physical therapies in combination has an important effect on hip pain, vaso-occlusive crises and acute chest syndrome. Trial authors did not report information on mortality and quality of life. The limited number of participants included in the study led to imprecise results, therefore, the confidence in the results is very low.
Abstract: Only two eligible trials were included (593 patients), both of reasonable quality although one was unblinded. Both trials compared selegiline with a dopamine agonist, whilst one also compared selegiline with levodopa. MAO-B inhibitors were not associated with a significant increase or decrease in deaths compared with levodopa (odds ratio (OR) 0.96; 95% confidence interval (CI) 0.52 to 1.76) or dopamine agonists (OR 1.30; 95% CI 0.69 to 2.45). Those receiving MAO-B inhibitors were more likely to require add-on therapy during follow-up than those receiving levodopa (OR 12.02; 95% CI 6.78 to 21.31) or dopamine agonist (OR 2.00; 95% CI 1.05 to 3.81). There was a reduction in motor fluctuations with MAO-B inhibitors compared with levodopa (OR 0.55; 95% CI 0.32 to 0.94) but not dopamine agonists (OR 1.15; 95% CI 0.65 to 2.05). Withdrawals due to adverse events were less common with MAO-B inhibitors than with dopamine agonists (OR 0.11; 95% CI 0.01 to 0.99). MAO-B inhibitors are one option for the early treatment of PD although they have weaker symptomatic effects than levodopa and dopamine agonists. They may reduce the rate of motor fluctuations compared with initial levodopa therapy and may have fewer significant adverse effects than the older agonists but data are too few to provide reliable conclusions.

Plain-language summary: We reviewed the trials that compared giving MAO-B inhibitors with other types of medication in people with early Parkinson's to see if there was good evidence that MAO-B inhibitors were the best treatment to offer. However, unfortunately we only identified two trials (593 patients) so there was only limited evidence. The results showed that MAO-B inhibitors were less good at improving the symptoms of Parkinson's than either levodopa or dopamine agonists but that they may reduce motor fluctuations compared with levodopa, though not compared with dopamine agonists. MAO-B inhibitors did, however, have fewer major side effects than some dopamine agonists.
Abstract: We included seven trials involving a total of 75 people with mild to moderate asthma. The studies were all of cross-over design. Six trials involving 55 people showed that in comparison with placebo, caffeine, even at a 'low dose' (less than 5 mg/kg body weight), appears to improve lung function for up to two hours after consumption. Forced expiratory volume in one second (FEV1) showed a small improvement up to two hours after caffeine ingestion (standardised mean difference 0.72; 95% confidence interval 0.25 to 1.20), which translates into a 5% mean difference in FEV1. However in two studies the mean differences in FEV1 were 12% and 18% after caffeine. Mid-expiratory flow rates also showed a small improvement with caffeine and this was sustained up to four hours. One trial involving 20 people examined the effect of drinking coffee versus a decaffeinated variety on the exhaled nitric oxide levels in patients with asthma and concluded that there was no significant effect on this outcome. Caffeine appears to improve airways function modestly, for up to four hours, in people with asthma. People may need to avoid caffeine for at least four hours prior to lung function testing, as caffeine ingestion could cause misinterpretation of the results. Drinking caffeinated coffee before taking exhaled nitric oxide measurements does not appear to affect the results of the test, but more studies are needed to confirm this.

Plain-language summary: This review carefully examines all the available high-quality clinical trials on caffeine in asthma. This review was conducted to discover if people should avoid consuming caffeine before taking lung function tests. This review found that even small amounts of caffeine can improve lung function for up to four hours. Therefore caffeine can affect the result of a lung function test (e.g. spirometry) and so caffeine should be avoided before taking a lung function test if possible, and previous caffeine consumption should be recorded. It is not known if taking caffeine leads to improvements in symptoms. It may be that in order to improve the symptoms of asthma, caffeine is needed in such large amounts that the drug's adverse effects would become a problem, so more research is needed. Another clinical trial looked at the effect of caffeine on exhaled nitric oxide levels and found that there is no significant effect, so it appears unlikely that patients would need to avoid caffeine before taking this type of test. However, this is the result of just a single study so more research is needed to clarify this.
Abstract: Three RCTs were identified, comprising a total of 847 participants. One trial compared silver-containing foam (Contreet®) with hydrocellular foam (Allevyn®) in patients with leg ulcers. The second trial compared a silver-containing alginate (Silvercel®) with an alginate alone (Algosteril®). The third trial compared a silver-containing foam dressing (Contreet®)) with best local practice in patients with chronic wounds. The data from these trials show that silver-containing foam dressings did not significantly increase complete ulcer healing as compared with standard foam dressings or best local practice after up to four weeks of follow-up, although a greater reduction of ulcer size was observed with the silver-containing foam. The use of antibiotics was assessed in two trials, but no significant differences were found. Data on pain, patient satisfaction, length of hospital stay, and costs were limited and showed no differences. Leakage occurred significantly less frequently in patients with leg ulcers and chronic wounds treated with a silver dressing than with a standard foam dressing or best local practice in one trial. Only three trials with a short follow-up duration were found. There is insufficient evidence to recommend the use of silver-containing dressings or topical agents for treatment of infected or contaminated chronic wounds.

Plain-language summary: Three studies looking at people with chronic wounds were included in the review and found that silver-containing foam dressings did not result in faster wound healing after up to four weeks of follow-up. One study did find that the overall size of the ulcer reduced more quickly when dressed with a silver-containing foam. There is no enough evidence to recommend the use of silver-containing dressings or topical agents for treating infected or contaminated chronic wounds.