GEM/cochrane-simplification huggingface dataset:
Abstract: This review includes a total of ten trials involving 544 acute asthma patients. Seven studies involved adults and three studies dealt solely with children. Three were assessed as high quality (Jadad score > 3). Pulmonary function tests were recorded during heliox administration (15 to 60 min). Pooling of the eight trials contributing data to this review showed no significant group differences (standardised mean differences -0.28; 95% confidence interval (CI) -0.56 to 0.01). There was significant heterogeneity among the studies. Heliox use did improve pulmonary function only in the subgroup of patients with the most severe baseline pulmonary function impairment; however, this conclusion is based on a small number of studies. There were no significant differences between groups when adults versus children, and high versus low heliox dose studies were compared. Finally, at the end of treatment, participants treated with heliox showed no significant different risk of admission to hospital (RR 0.83 (95%CI 0.66 to 1.08, P = 0.17, I2 = 0%). The existing evidence does not provide support for the administration of helium-oxygen mixtures to all ED patients with acute asthma. At this time, heliox treatment does not have a role to play in the initial treatment of patients with acute asthma. Nevertheless, new evidence suggests certain beneficial effects in patients with more severe obstruction. Since these conclusions are based upon between-group comparisons and small studies, they should be interpreted with caution.

Plain-language summary: This review examines the evidence from ten randomised controlled trials involving 544 patients which compared heliox to oxygen or air, when used in conjunction with the other standard acute treatments. The reviewers conclude that the evidence does not support routine use of heliox in patients with acute asthma.
Abstract: We identified no new studies with available results for this update. The earlier review included 20 studies (7238 participants) in valid comparisons, but because we used different outcomes for some headache studies, the number of participants in the analyses of the effects of caffeine is now 4262 when previously it was 5243. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement, although many of those treating postoperative pain were small. Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum over four to six hours) with the addition of caffeine, giving a NNT of about 14 (high quality evidence). Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication. We know of the existence of around 25 additional studies with almost 12,500 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; the bulk of the unobtainable data are reported to have similar results as this review. The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.

Plain-language summary: This review examined whether caffeine improves the pain-relieving effects of such medicines. We searched for studies up to August 2014 and included twenty studies (7238 participants) examining several pain conditions, including headache, post-dental pain, postoperative pain following childbirth, and menstrual period pain. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement. Many of those in post-dental and postoperative pain were small, and small studies can overestimate benefits. A dose of caffeine equivalent to a mug of coffee added to a standard dose of common analgesics such as paracetamol or ibuprofen provided better pain relief. Analgesic plus caffeine increased the number of people who had a good level of pain relief by 5% to 10% compared with analgesic alone (high quality evidence). No serious adverse events were reported that were related to either the analgesic or caffeine in these studies (low quality evidence). It is unlikely that adding caffeine to an analgesic will be harmful if the recommended dose is not exceeded.
Abstract: We included nine trials in the review (eight randomised controlled studies and one controlled trial) with a total of 453,965 subjects. In one large study that included both smokers and non-smokers comparing annual chest x-ray screening with usual care there was no reduction in lung cancer mortality (RR 0.99, 95% CI 0.91 to 1.07). In a meta-analysis of studies comparing different frequencies of chest x-ray screening, frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, 95% CI 1.00 to 1.23); however several of the trials included in this meta-analysis had potential methodological weaknesses. We observed a non-statistically significant trend to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, 95% CI 0.74 to 1.03). There was one large methodologically rigorous trial in high-risk smokers and ex-smokers (those aged 55 to 74 years with ≥ 30 pack-years of smoking and who quit ≤ 15 years prior to entry if ex-smokers) comparing annual low-dose CT screening with annual chest x-ray screening; in this study the relative risk of death from lung cancer was significantly reduced in the low-dose CT group (RR 0.80, 95% CI 0.70 to 0.92). The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Annual low-dose CT screening is associated with a reduction in lung cancer mortality in high-risk smokers but further data are required on the cost effectiveness of screening and the relative harms and benefits of screening across a range of different risk groups and settings.

Plain-language summary: Trials were made of early detection methods such as the testing of sputum, x-ray and computed tomography (CT) scanning of the chest to see whether they made a difference to the number of people who were treated by surgery and the number of people who died as a result of the disease. This review examined the evidence from nine trials (with a total of 453,965 participants) and found that early screening with chest X-ray or sputum testing does not reduce the number of people who die from lung cancer. Screening with low-dose chest CT was found in one large trial to reduce the number of people who die from lung cancer but this trial only included very high-risk smokers and ex-smokers. CT screening however is associated with a high number of false positive results and there are also some people who have lung cancer detected and treated but in whom this cancer may not have progressed to cause death in their lifetime, even in the absence of treatment (referred to as overdiagnosis). More research is needed about the relative harms and benefits of CT screening in individuals at lower risk for lung cancer.
Abstract: We identified seven studies enrolling 767 patients and with 830 catheter insertions. Three of seven studies described the method of random sequence generation, none described allocation concealment, and blinding of participants and personnel was not possible. Real-time ultrasound guidance was found to significantly reduce the risk of catheter placement failure on the first attempt (5 studies, 595 catheters): RR 0.40, 95% CI 0.30 to 0.52), significantly reduce the risk of arterial puncture (6 studies, 535 catheters: RR 0.13, 95% CI 0.04 to 0.37) and haematomas (4 studies, 323 catheters: RR 0.22, 95% CI 0.06 to 0.81) when compared to the landmark method. The time taken for successful cannulation was significantly lower with the use of real-time ultrasound guidance (1 study, 73 catheters: MD -1.40 min, 95% CI -2.17 to -0.63) and there were less attempts/catheter insertion (1 study, 110 catheters: -0.35, 95% CI -0.54 to -0.16). Use of real-time 2-D Doppler ultrasound guidance has significant benefits with respect to the number of catheters successfully inserted on the first attempt, reduction in the risk of arterial puncture and haematomas and the time taken for successful vein puncture.

Plain-language summary: We identified seven studies, enrolling 767 patients that compared haemodialysis catheter insertion using the traditional 'blind' landmark method and insertion using ultrasound imaging. The use of ultrasound imaging was found to be associated with significantly less risk of arterial puncture and haematomas and less time to insert the catheter as well as a higher success rate for inserting the catheter on the first attempt.
Abstract: From 17 studies, only two met our inclusion criteria. Together they had 280 participants aged between 18 and 45 years. One hundred and fifteen yielded analysable results. Both studies measured symptom severity using subjective scales. Differing in design, participants, dose of progesterone and how delivered, the studies could not be combined in meta-analysis. Adverse events which may or may not have been side effects of the treatment were described as mild. Both trials had defects. They intended to exclude women whose symptoms continued after their periods. When data from ineligible women were excluded from analysis in one trial, the other women were found to have benefited more from progesterone than placebo. The smaller study found no statistically significant difference between oral progesterone, vaginally absorbed progesterone and placebo, but reported outcomes incompletely. The trials did not show that progesterone is an effective treatment for PMS nor that it is not. Neither trial distinguished a subgroup of women who benefited, nor examined claimed success with high doses.

Plain-language summary: This review found some evidence for relief with progesterone but trials differed in route of administration, dose, duration of treatment and selection of women taking part. Outcomes also differed. The studies had flaws in methods or in handling outcome data or both. Adverse effects which may or may not have been the result of the treatment were generally mild. Further research would be needed to test claims for the effectiveness of higher doses of progesterone. They are neither refuted nor borne out as yet. Using each woman's own symptoms to select participants and to judge treatment effects would be more accurate than checklists of largely irrelevant symptoms. Knowing how many women had fewer days with symptoms, fewer or milder symptoms, or the converse, would be more valuable than the calculations based on subjective data for groups of women.
Abstract: Many of the trials were from low-income countries; they were generally small and frequently methodologically poor. They covered a very wide range of differing drugs, doses and routes of administration, making it difficult to pool data. Oral iron in pregnancy showed a reduction in the incidence of anaemia (risk ratio 0.38, 95% confidence interval 0.26 to 0.55, one trial, 125 women) and better haematological indices than placebo (two trials). It was not possible to assess the effects of treatment by severity of anaemia. A trend was found between dose and reported adverse effects. Most trials reported no clinically relevant outcomes nor adverse effects. Although the intramuscular and intravenous routes produced better haematological indices in women than the oral route, no clinical outcomes were assessed and there were insufficient data on adverse effects, for example, on venous thrombosis and severe allergic reactions. Daily low-dose iron supplements may be effective at treating anaemia in pregnancy with less gastrointestinal side effects compared with higher doses. Despite the high incidence and burden of disease associated with this condition, there is a paucity of good quality trials assessing clinical maternal and neonatal effects of iron administration in women with anaemia. Daily oral iron treatment improves haematological indices but causes frequent gastrointestinal adverse effects. Parenteral (intramuscular and intravenous) iron enhances haematological response, compared with oral iron, but there are concerns about possible important adverse effects (for intravenous treatment venous thrombosis and allergic reactions and for intramuscular treatment important pain, discolouration and allergic reactions). Large, good quality trials, assessing clinical outcomes (including adverse effects) as well as the effects of treatment by severity of anaemia are required.

Plain-language summary: In this review, we identified 23 trials involving 3198 pregnant women. Many of the trials were in low-income countries and many treatment variations were studied. Oral iron reduced the incidence of anaemia but is known to sometimes cause constipation and nausea. Although the intramuscular and intravenous routes produced better levels of red cells and iron stores than the oral route, no clinical outcomes (such as pre-eclampsia, preterm births, postpartum haemorrhage) were assessed and there were insufficient data on adverse effects. Intravenous treatment can cause venous thrombosis (blockages in the veins) and intramuscular treatment causes important pain and discolouration at the injection site. It was unclear if women and babies were healthier when women were given iron for mild or moderate anaemia during pregnancy. There were no studies on using blood transfusions. Overall, there was insufficient evidence to say when or how anaemia in pregnancy needs to or should be treated.
Abstract: Four trials (three RCTs and one quasi-RCT) involving 355 children were included. Children using symptom-based WAPs had lower risk of exacerbations which required an acute care visit (N = 5; RR 0.73; 95% CI 0.55 to 0.99). The number needed to treat to prevent one acute care visit was 9 (95% CI 5 to 138). Symptom monitoring was preferred over peak flow monitoring by children (N = 2; RR 1.21; 95% CI 1.00 to 1.46), but parents showed no preference (N = 2; RR 0.96; 95% CI 0.18 to 2.11). Children assigned to peak flow-based action plans reduced by 1/2 day the number of symptomatic days per week (N = 2; mean difference: 0.45 days/week; 95% CI 0.04 to 0.26). There were no significant group differences in the rate of exacerbation requiring oral steroids or admission, school absenteeism, lung function, symptom score, quality of life, and withdrawals. The evidence suggests that symptom-based WAP are superior to peak flow WAP for preventing acute care visits although there is insufficient data to firmly conclude whether the observed superiority is conferred by greater adherence to the monitoring strategy, earlier identification of onset of deteriorations, higher threshold for presentation to acute care settings, or the specific treatment recommendations.

Plain-language summary: Four clinical trials with 355 children were identified which compared the effect of symptom-based versus to peak flow written action plans when all other co-interventions were similar. Children assigned to a symptom-based plan less frequently required an acute care visit for asthma compared to those who received a peak flow based plan. Most other outcomes were similar with the exception of more children intending to continue using the symptom-based compared to the peak-flow based written action plan.
Abstract: We included 68 studies in which aspirin was used at doses from 300 mg to 1200 mg, but the vast majority of participants received either 600/650 mg (2409 participants, 64 studies) or 990/1000 mg (380 participants, eight studies). There was only one new study. Studies were overwhelmingly of adequate or good methodological quality. NNTs for at least 50% pain relief over four to six hours were 4.2 (3.9 to 4.8), 3.8 (3.0 to 5.1), and 2.7 (2.0 to 3.8) for 600/650 mg, 900/1000 mg, and 1200 mg respectively, compared with placebo. Type of pain model had no significant impact on the results. Lower doses were not significantly different from placebo. These results do not differ from those of the earlier review. Fewer participants required rescue medication with aspirin than with placebo over four to eight hours postdose, but by 12 hours there was no difference. The number of participants experiencing adverse events was not significantly different from placebo for 600/650 mg aspirin, but for 900/1000 mg the number needed to treat to harm was 7.5 (4.8 to 17). The most commonly reported events were dizziness, drowsiness, gastric irritation, nausea, and vomiting, nearly all of which were of mild to moderate severity. Aspirin is an effective analgesic for acute pain of moderate to severe intensity. High doses are more effective, but are associated with increased adverse events, including drowsiness and gastric irritation. The pain relief achieved with aspirin was very similar milligram for milligram to that seen with paracetamol. There was no change to the conclusions in this update.

Plain-language summary: This review assessed both the pain-relieving effectiveness and the adverse effects of a single dose of aspirin in acute postoperative pain of moderate to severe intensity. We included 67 studies, with 3111 participants given aspirin in comparisons with 2632 given placebo. Most of the information was for a 600 mg or 650 mg dose. The results confirm that in patients with moderate to severe postoperative pain, about 40% of those treated with aspirin 600/650 mg will experience good levels of pain relief, compared with about 15% treated with placebo. This level of pain relief is comparable to that experienced with the same dose of paracetamol. In these single dose studies there was no significant difference between aspirin 600/650 mg and placebo for the number of participants experiencing adverse events, but at 900/1000 mg, twice as many did so, with dizziness, drowsiness, gastric irritation, nausea, and vomiting being the most common events reported.
Abstract: Twenty RCTs (mean trial duration 10 months) including 1,811 participants, with mean age 59.8 years and mean known duration of diabetes 9.6 years. Overall, study methodological quality was low. Twenty-eight comparisons in 20 RCTs were ordered according to clinical considerations. No studies assessed diabetes-related morbidity, mortality or total mortality. From 13 studies (21 comparisons), sufficient data were extracted to calculate pooled effects on glycaemic control. Insulin-OHA combination therapy had statistically significant benefits on glycaemic control over insulin monotherapy only when the latter was applied as a once-daily injection of NPH insulin. Conversely, twice-daily insulin monotherapy (NPH or mixed insulin) provided superior glycaemic control to insulin-OHA combination therapy regimens where insulin was administered as a single morning injection. In more conventional comparisons, regimens utilising OHAs with bedtime NPH insulin provided comparable glycaemic control to insulin monotherapy (administered as twice daily, or multiple daily injections). Overall, insulin-OHA combination therapy was associated with a 43% relative reduction in total daily insulin requirement compared to insulin monotherapy. Of the 14 studies (22 comparisons) reporting hypoglycaemia, 13 demonstrated no significant difference in the frequency of symptomatic or biochemical hypoglycaemia between insulin and combination therapy regimens. No significant differences in quality of life related issues were detected. Combination therapy with bedtime NPH insulin resulted in statistically significantly less weight gain compared to insulin monotherapy, provided metformin was used ± sulphonylurea. In all other comparisons no significant differences with respect to weight gain were detected. Bedtime NPH insulin combined with oral hypoglycaemic agents provides comparable glycaemic control to insulin monotherapy and is associated with less weight gain if metformin is used.

Plain-language summary: Simple application of a single daily insulin injection in addition to oral hypoglycaemic agents may facilitate the initiation of insulin therapy in type 2 diabetes mellitus.This review examined 20 trials including 1,811 participants which compared insulin monotherapy with insulin in combination with oral hypoglycaemic agents (OHA) in insulin-requiring patients with type 2 diabetes. The results suggest that a bedtime NPH insulin-oral hypoglycaemic agent combination therapy regimen provides comparable glycaemic control to insulin monotherapy. Due to lack of studies it remains unclear whether insulin-OHA combination regimens with metformin alone are superior to those with metformin plus a sulphonylurea. In most cases no significant differences in hypoglycaemic events were observed between insulin mono- and OHA combination therapy. No study assessed diabetes-related morbidity or mortality.
Abstract: Two published trials were identified that randomised a total of 119 people. In one study conducted in France, 20 people were randomly allocated to Gingko biloba extract EGb 761 80 mg twice daily or placebo. In the other study conducted in Germany, 99 people were randomly allocated to two different doses of Ginkgo biloba extract EGb 761 (240 mg per day and 60 mg per day). Treatment duration in both studies was six months. Both trials reported some positive effects of Ginkgo biloba on vision however their results could not be pooled. Adverse effects and quality of life for people with AMD were not reported. The question as to whether people with AMD should take Ginkgo biloba extract to prevent progression of the disease has not been answered by research to date. Two small trials have suggested possible benefit of Gingko biloba on vision and further trials are warranted. Ginkgo biloba is widely used in China, Germany, and France. Future trials should be larger, and last longer, in order to provide a more robust measure of the effect of Gingko biloba extract on AMD.

Plain-language summary: The author identified two small randomised controlled studies (with a total of 119 participants); one in France and one in Germany. One trial compared Gingko biloba to placebo and the other compared two different doses of the extract. Although both trials reported some positive effects of Ginkgo biloba on vision, the trials were small and of short duration. Adverse effects and quality of life were not assessed. The overall conclusion of this review is that current research has not answered the question as to whether Ginkgo biloba is of benefit to people with AMD. Future trials need to include a larger number of participants and be conducted over a longer time.