[
    {
        "index": "cochrane-simplification-test-0",
        "sentence": "A total of 38 studies involving 7843 children were included. Following educational intervention delivered to children, their parents or both, there was a significantly reduced risk of subsequent emergency department visits (RR 0.73, 95% CI 0.65 to 0.81, N = 3008) and hospital admissions (RR 0.79, 95% CI 0.69 to 0.92, N = 4019) compared with control. There were also fewer unscheduled doctor visits (RR 0.68, 95% CI 0.57 to 0.81, N = 1009). Very few data were available for other outcomes (FEV1, PEF, rescue medication use, quality of life or symptoms) and there was no statistically significant difference between education and control. Asthma education aimed at children and their carers who present to the emergency department for acute exacerbations can result in lower risk of future emergency department presentation and hospital admission. There remains uncertainty as to the long-term effect of education on other markers of asthma morbidity such as quality of life, symptoms and lung function. It remains unclear as to what type, duration and intensity of educational packages are the most effective in reducing acute care utilisation.",
        "gold": "This review looked at studies which compared usual care for asthma to more intensive educational programmes and the results showed a statistically significant reduction in the treatment groups needing subsequent emergency department visits or hospital admissions. We were not able to determine the most effective type, duration or intensity of education that should be offered to children to offer the best asthma outcomes."
    },
    {
        "index": "cochrane-simplification-test-1",
        "sentence": "We included 130 studies with 8341 participants. Ketamine was given to 4588 participants and 3753 participants served as controls. Types of surgery included ear, nose or throat surgery, wisdom tooth extraction, thoracotomy, lumbar fusion surgery, microdiscectomy, hip joint replacement surgery, knee joint replacement surgery, anterior cruciate ligament repair, knee arthroscopy, mastectomy, haemorrhoidectomy, abdominal surgery, radical prostatectomy, thyroid surgery, elective caesarean section, and laparoscopic surgery. Racemic ketamine bolus doses were predominantly 0.25 mg to 1 mg, and infusions 2 to 5 \u00b5g/kg/minute; 10 studies used only S-ketamine and one only R-ketamine. Risk of bias was generally low or uncertain, except for study size; most had fewer than 50 participants per treatment arm, resulting in high heterogeneity, as expected, for most analyses. We did not stratify the main analysis by type of surgery or any other factor, such as dose or timing of ketamine administration, and used a non-stratified analysis. Perioperative intravenous ketamine reduced postoperative opioid consumption over 24 hours by 8 mg morphine equivalents (95% CI 6 to 9; 19% from 42 mg consumed by participants given placebo, moderate-quality evidence; 65 studies, 4004 participants). Over 48 hours, opioid consumption was 13 mg lower (95% CI 10 to 15; 19% from 67 mg with placebo, moderate-quality evidence; 37 studies, 2449 participants). Perioperative intravenous ketamine reduced pain at rest at 24 hours by 5/100 mm on a visual analogue scale (95% CI 4 to 7; 19% lower from 26/100 mm with placebo, high-quality evidence; 82 studies, 5004 participants), and at 48 hours by 5/100 mm (95% CI 3 to 7; 22% lower from 23/100 mm, high-quality evidence; 49 studies, 2962 participants). Pain during movement was reduced at 24 hours (6/100 mm, 14% lower from 42/100 mm, moderate-quality evidence; 29 studies, 1806 participants), and 48 hours (6/100 mm, 16% lower from 37 mm, low-quality evidence; 23 studies, 1353 participants). Results for primary outcomes were consistent when analysed by pain at rest or on movement, operation type, and timing of administration, or sensitivity to study size and pain intensity. No analysis by dose was possible. There was no difference when nitrous oxide was used. We downgraded the quality of the evidence once if numbers of participants were large but small-study effects were present, or twice if numbers were small and small-study effects likely but testing not possible. Ketamine increased the time for the first postoperative analgesic request by 54 minutes (95% CI 37 to 71 minutes), from a mean of 39 minutes with placebo (moderate-quality evidence; 31 studies, 1678 participants). Ketamine reduced the area of postoperative hyperalgesia by 7 cm\u00b2 (95% CI \u221211.9 to \u22122.2), compared with placebo (very low-quality evidence; 7 studies 333 participants). We downgraded the quality of evidence because of small-study effects or because the number of participants was below 400. CNS adverse events occurred in 52 studies, while 53 studies reported of absence of CNS adverse events. Overall, 187/3614 (5%) participants receiving ketamine and 122/2924 (4%) receiving control treatment experienced an adverse event (RR 1.2, 95% CI 0.95 to 1.4; high-quality evidence; 105 studies, 6538 participants). Ketamine reduced postoperative nausea and vomiting from 27% with placebo to 23% with ketamine (RR 0.88, 95% CI 0.81 to 0.96; the number needed to treat to prevent one episode of postoperative nausea and vomiting with perioperative intravenous ketamine administration was 24 (95% CI 16 to 54; high-quality evidence; 95 studies, 5965 participants). Perioperative intravenous ketamine probably reduces postoperative analgesic consumption and pain intensity. Results were consistent in different operation types or timing of ketamine administration, with larger and smaller studies, and by higher and lower pain intensity. CNS adverse events were little different with ketamine or control. Perioperative intravenous ketamine probably reduces postoperative nausea and vomiting by a small extent, of arguable clinical relevance.",
        "gold": "In July 2018 we searched for randomised clinical trials where ketamine was injected before, during, or after operation in adults having an operation under general anaesthesia. Important outcomes were opioid use and pain at 24 and 48 hours after the operation, time to first request for a painkiller, and ketamine-related side effects. We found 130 eligible studies with 8341 participants. Compared to people given control treatment, those given intravenous ketamine used less opioid painkiller (by about 1 part in 10), and had less pain (by about 2 parts in 10; moderate- or high-quality evidence). Ketamine may be more effective in operations that are likely to cause more intense pain. People given ketamine requested painkillers 54 minutes later than those who did not receive ketamine (moderate-quality evidence). Ketamine reduced the risk of postoperative nausea and vomiting by a small amount (high-quality evidence). Ketamine produced no increased risk of central nervous system side effects (hallucination, nightmares or double vision) (high-quality evidence). Future research should assess ketamine's effect after operations that are accompanied by intense pain such as thoracotomy, back surgery, or amputations. Additionally, assessing ketamine's effects among particular patient groups, for example, the elderly or individuals with a history of substance abuse would be of interest. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. We found the quality of evidence for most outcomes to be moderate. Many of the studies were small, which was the main reason for downgrading the evidence from high to moderate. We tested the results by operation type, timing of ketamine injection, and by looking at larger studies, and those with more pain were consistent, and provided confidence in the results. There was sufficient evidence to allow conclusions about ketamine's effect on pain, painkiller consumption and side effects after operation."
    },
    {
        "index": "cochrane-simplification-test-2",
        "sentence": "Five trials of MSP/RESA vaccine with 217 participants were included; all five reported on safety, and two on efficacy. No severe or systemic adverse effects were reported at doses of 13 to 15 \u00b5g of each antigen (39 to 45 \u00b5g total). One small efficacy trial with 17 non-immune participants with blood-stage parasites showed no reduction or delay in parasite growth rates after artificial challenge. In the second efficacy trial in 120 children aged five to nine years in Papua New Guinea, episodes of clinical malaria were not reduced, but MSP/RESA significantly reduced parasite density only in children who had not been pretreated with an antimalarial drug (sulfadoxine-pyrimethamine). Infections with the 3D7 parasite subtype of MSP2 (the variant included in the vaccine) were reduced (RR 0.38, 95% CI 0.26 to 0.57; 719 participants) while those with the other main subtype, FC27, were not (720 participants). The MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific. Pretreatment for malaria during a vaccine trial makes the results difficult to interpret, particularly with the relatively small sample sizes of early trials. The results show that blood-stage vaccines may play a role and merit further development.",
        "gold": "This review looked at vaccinations targeted at the asexual (blood) phase of the parasite's life, when the parasites are in red blood cells. One vaccine for this phase, MSP/RESA (also known as Combination B), has been tested in field trials in Papua New Guinea. It reduced the density of parasites in the blood, but it did not prevent malaria attacks. Blood-stage vaccines are being actively pursued in further research."
    },
    {
        "index": "cochrane-simplification-test-3",
        "sentence": "Four studies, involving 125 participants, were included. Three studies evaluated the effects of pulsed electromagnetic fields and one study, capacitive coupled electric fields. Participants with delayed union and non-union of the long bones were included, but most data related to non-union of the tibia. Although all studies were blinded randomised placebo-controlled trials, each study had limitations. The primary measure of the clinical effectiveness of electromagnetic field stimulation was the proportion of participants whose fractures had united at a fixed time point. The overall pooled effect size was small and not statistically significant (risk ratio 1.96; 95% confidence interval 0.86 to 4.48; 4 trials). There was substantial clinical and statistical heterogeneity in this pooled analysis (I2 = 58%). A sensitivity analysis conducted to determine the effect of multiple follow-up time-points on the heterogeneity amongst the studies showed that the effect size remained non-significant at 24 weeks (risk ratio 1.61; 95% confidence interval 0.74 to 3.54; 3 trials), with similar heterogeneity (I2 = 57%). There was no reduction in pain found in two trials. No study reported functional outcome measures. One trial reported two minor complications resulting from treatment. Though the available evidence suggests that electromagnetic field stimulation may offer some benefit in the treatment of delayed union and non-union of long bone fractures, it is inconclusive and insufficient to inform current practice. More definitive conclusions on treatment effect await further well-conducted randomised controlled trials.",
        "gold": "Four studies, which involved 125 participants, were included in this review. The majority of participants had suffered a broken tibia that had not healed as quickly as expected or at all. The results of this review suggest that there may be a benefit on bone healing from electromagnetic field stimulation. However, the available evidence was not good enough to be certain of this and it may not apply to current practice. Electromagnetic field stimulation appears to be safe. The two complications reported were minor involving irritation of the skin."
    },
    {
        "index": "cochrane-simplification-test-4",
        "sentence": "A total of 1831 participants were randomised to drain (915 participants) versus 'no drain' (916 participants) in 12 trials included in this review. Only two trials including 199 participants were of low risk of bias. Nine trials included patients undergoing elective laparoscopic cholecystectomy exclusively. One trial included patients undergoing laparoscopic cholecystectomy for acute cholecystitis exclusively. One trial included patients undergoing elective and emergency laparoscopic cholecystectomy, and one trial did not provide this information. The average age of participants in the trials ranged between 48 years and 63 years in the 10 trials that provided this information. The proportion of females ranged between 55.0% and 79.0% in the 11 trials that provided this information. There was no significant difference between the drain group (1/840) (adjusted proportion: 0.1%) and the 'no drain' group (2/841) (0.2%) (RR 0.41; 95% CI 0.04 to 4.37) in short-term mortality in the ten trials with 1681 participants reporting on this outcome. There was no significant difference between the drain group (7/567) (adjusted proportion: 1.1%) and the 'no drain' group (3/576) (0.5%) in the proportion of patients who developed serious adverse events in the seven trials with 1143 participants reporting on this outcome (RR 2.12; 95% CI 0.67 to 7.40) or in the number of serious adverse events in each group reported by eight trials with 1286 participants; drain group (12/646) (adjusted rate: 1.5 events per 100 participants) versus 'no drain' group (6/640) (0.9 events per 100 participants); rate ratio 1.60; 95% CI 0.66 to 3.87). There was no significant difference in the quality of life between the two groups (one trial; 93 participants; SMD 0.22; 95% CI -0.19 to 0.63). The proportion of patients who were discharged as day-procedure laparoscopic cholecystectomy seemed significantly lower in the drain group than the 'no drain' group (one trial; 68 participants; drain group (0/33) (adjusted proportion: 0.2%) versus 'no drain' group (11/35) (31.4%); RR 0.05; 95% CI 0.00 to 0.75). There was no significant difference in the length of hospital stay between the two groups (five trials; 449 participants; MD 0.22 days; 95% CI -0.06 days to 0.51 days). The operating time was significantly longer in the drain group than the 'no drain' group (seven trials; 775 participants; MD 5.00 minutes; 95% CI 2.69 minutes to 7.30 minutes). There was no significant difference in the return to normal activity and return to work between the groups in one trial involving 100 participants. This trial did not provide any information from which the standard deviation could be imputed and so the confidence intervals could not be calculated for these outcomes. There is currently no evidence to support the routine use of drain after laparoscopic cholecystectomy. Further well designed randomised clinical trials are necessary.",
        "gold": "A total of 1831 participants received drain (915 patients) versus 'no drain' (916 patients) in 12 trials included in this review. The decision of whether the patients received drain or not was determined by a method similar to toss of a coin. Only two trials including 199 patients were of low risk of bias (free from errors in study design that can result in wrong conclusions, leading to overestimation of benefits and to underestimation of harms of the drainage or no drainage). Nine of the 12 trials included patients who underwent planned operations. The average age of participants in the trials ranged between 48 years and 63 years in the 10 trials that provided this information. The proportion of females ranged between 55.0% and 79.0% in the 11 trials that provided this information. There was no significant or clinically important differences in the short-term mortality, serious complications, quality of life, length of hospital stay, operating time, return to normal activity, or return to work in the trials that reported these outcomes. The proportion of patients who were discharged as day-procedure laparoscopic cholecystectomy seemed significantly lower in the drain group than in the 'no drain' group in one trial of high risk of bias involving 68 participants. Currently, there is no evidence to support the use of drain after laparoscopic cholecystectomy. Further well-designed randomised clinical trials are necessary."
    },
    {
        "index": "cochrane-simplification-test-5",
        "sentence": "Forty-nine randomised trials involving 3639 participants were included. All trials were conducted and published in China. Thirty-eight different herbal medicines were tested in these trials, including four single herbs (extracts from a single herb), eight traditional Chinese patent medicines, and 26 self concocted Chinese herbal compound prescriptions. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve conduction velocity. The positive results described from the 49 studies of low quality are of questionable significance. There was inadequate reporting on adverse events in the included trials. Eighteen trials found no adverse events. Two trials reported adverse events: adverse events occurred in the control group in one trial, and in the other it was unclear in which group the adverse events occurred. 29 trials did not mention whether they monitored adverse events. Conclusions cannot be drawn from this review about the safety of herbal medicines, due to inadequate reporting. Most of the trials were of very low methodological quality and therefore the interpretation of any positive findings for the efficacy of the included Chinese herbal medicines for treating diabetic peripheral neuropathy should be made with caution. Based on this systematic review, there is no evidence to support the objective effectiveness and safety of Chinese herbal medicines for diabetic peripheral neuropathy. No well-designed, randomised, placebo controlled trial with objective outcome measures has been conducted.",
        "gold": "This systematic review identified a total of 49 trials that included 3639 participants with DPN. Ten of the trials were new at this first update of the review. We evaluated the effects of various herbal formulations (including single herbs, Chinese proprietary medicines and mixtures of different herbs) for treating people with DPN. All the identified clinical trials were performed and published in China. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve conduction velocity. The positive results described from the 49 studies of low quality are of questionable significance. There was inadequate reporting on adverse events in the included trials. Most of the trials did not mention whether they monitored for adverse effects. Only two trials reported adverse events but an adverse event occurred in the control group in one trial and it was unclear in which group they occurred in the other trial. Conclusions about the safety of herbal medicines cannot therefore be drawn from this review due to inadequate reporting. Most of the trials were of very low methodological quality and the interpretation of any positive findings for the efficacy of the included Chinese herbal medicines for treating DPN should be made with caution. Based on this systematic review, there is no evidence to support the objective effectiveness and safety of Chinese herbal medicines for DPN. No well-designed, randomised placebo controlled trial with objective outcome measures has been conducted."
    },
    {
        "index": "cochrane-simplification-test-6",
        "sentence": "Five randomized studies involving 1382 patients were included in this review. All the included studies involved advanced (T3 or T4) prostate cancer, had relatively small populations, and were of short duration. Few events were reported and did not assess disease-specific survival or metastatic disease. Only one study (N = 77) evaluated biochemical outcomes. A subgroup analysis found no significant differences in biochemical progression (defined by the authors as PSA \u2265 10 ng/mL) between IAS and CAS for Gleason scores 4 - 6, 7, and 8 - 10. For patients with a Gleason score > 6, reduction in biochemical progression favoured the IAS group (RR 0.10, 95% CI 0.01 to 0.67, P = 0.02). Studies primarily reported on adverse events. One trial (N = 43) found no difference in adverse effects (gastrointestinal, gynecomastia and asthenia) between IAS ( two events) and CAS (five events), with the exception of impotence, which was significantly lower in the IAS group (RR 0.72, 95% CI 0.56 to 0.92, P = 0.008). Data from RCTs comparing IAS to CAS are limited by small sample size and short duration. There are no data for the relative effectiveness of IAS versus CAS for overall survival, prostate cancer-specific survival, or disease progression. Limited information suggests IAS may have slightly reduced adverse events. Overall, IAS was also as effective as CAS for potency, but was superior during the interval of cycles (96%).",
        "gold": "Five studies involving 1382 patients were included in this review. All the included studies involved advanced (T3 or T4) prostate cancer. No study was of adequate size and duration. Few events were reported and they did not assess disease-specific survival or metastatic disease. Only one study evaluated biochemical outcomes. Studies primarily reported on adverse events. There are no data for the relative effectiveness of IAS versus CAS for overall survival, prostate cancer specific survival, disease progression, or quality of life. Limited information suggests IAS may have slightly reduced adverse events. In Hering 2000, IAS (18/25 versus 18/18) appears to be slightly more favorable than CAS in controlling impotence. Overall, IAS was also as effective as CAS for potency, but was superior during the interval of cycles (96%). More research is needed."
    },
    {
        "index": "cochrane-simplification-test-7",
        "sentence": "We identified 12 trials most of which are of moderate risk of bias involving 7,119 participants which described random assignment. Five trials randomised to either immediate or delayed insertion of IUD. One of them randomised to immediate versus delayed insertion of Copper 7 showed immediate insertion of the Copper 7 was associated with a higher risk of expulsion than was delayed insertion (RR 11.98, 95% CI 1.61 to 89.35,1 study, 259 participants); the quality of evidence was moderate. Moderate quality of evidence also suggests that use and expulsion of levonorgestrel-releasing intrauterine system or CuT380A was more likely for immediate compared to delayed insertion risk ratio (RR) 1.40 (95% CI 1.24 to 1.58; 3 studies; 878 participants) and RR 2.64 ( 95% CI 1.16 to 6.00; 3 studies; 878 participants) respectively. Another trial randomised to the levonorgestrel IUD or Nova T showed discontinuation rates due to pregnancy were likely to be higher for women in the Nova T group. (MD 8.70, 95% CI 3.92 to 13.48;1 study; 438 participants); moderate quality evidence. Seven trials examined immediate insertion of IUD only. From meta-analysis of two multicentre trials, pregnancy was less likely for the TCu 220C versus the Lippes Loop (RR 0.43, 95% CI 0.24 to 0.75; 2 studies; 2257 participants ) as was expulsion (RR 0.61, 95% CI 0.46 to 0.81; 2 studies; 2257 participants). Estimates for the TCu 220 versus the Copper 7 were RR 0.42 ( 95% CI 0.23 to 0.77; 2 studies, 2,274 participants) and RR 0.68, (95% CI 0.51 to 0.91); 2 studies, 2,274 participants), respectively. In other work, adding copper sleeves to the Lippes Loop improved efficacy (RR 3.40, 95% CI 1.28 to 9.04, 1 study, 400 participants) and reduced expulsion (RR 3.00, 95% CI 1.51 to 5.97; 1 study, 400 participants). Moderate quality evidence shows that insertion of an IUD immediately after abortion is safe and practical. IUD expulsion rates appear higher immediately after abortions compared to delayed insertions. However, at six months postabortion, IUD use is higher following immediate insertion compared to delayed insertion.",
        "gold": "We did computer searches for randomised trials of IUDs inserted right after abortion or miscarriage. We also wrote to researchers to find more studies. Trials could compare types of IUDs or times for insertion. We found 12 studies to include. Four trials randomised women to an IUD inserted right away or at a later time. One had no major difference. Three recent trials (of levonorgestrel intrauterine system or CuT380A) showed use was greater at six months for an IUD inserted right away compared to one inserted later. Another trial assigned women to the levonorgestrel IUD or Nova T; more women with the Nova T stopped use due to pregnancy. A subanalysis showed more IUDs came out when inserted right after abortion or miscarriage rather than later. Seven trials looked at inserting the IUD right away. From two large trials, the TCu 220C was better than the Lippes Loop and the Copper 7 for preventing pregnancy and staying in. The IUD was more likely to come out on its own when inserted after a mid-pregnancy abortion than after an earlier one. In other work, when the Lippes Loop had copper arms added, fewer women got pregnant and the IUD stayed in more often. Moderate level evidence shows that inserting an IUD right after an abortion or miscarriage is safe and practical. However, the IUD is more likely to come out when inserted right away rather than at a later time. Women are more likely to use an IUD at six months if they had it inserted right away compared to some weeks after the abortion or miscarriage."
    },
    {
        "index": "cochrane-simplification-test-8",
        "sentence": "We included only one small trial published as an abstract article. The included study investigated the effects of meditation practice on patients newly hospitalised with acute leukaemia. Ninety-one participants enrolled in the study, but only 42 participants remained in the trial throughout the six-month follow-up period and were eligible for analysis. There was no information provided about the average age and sex of the study population. We found a high risk for attrition bias and unclear risk for reporting bias, performance and detection bias because of missing data due to abstract publication only, thus we judged the overall risk of bias as high. According to the GRADE criteria, we judged the overall quality of the body of evidence for all predefined outcomes as 'very low', due to the extent of missing data on the study population, and the small sample size. As the abstract publication did not provide numbers and results except P values, we are not able to give more details. Meditation practice might be beneficial for the quality of life of haematologically-diseased patients, with higher scores for participants in the mediation arms compared to the participants in the usual care control group (low quality of evidence). Levels of depression decreased for those practising meditation in both the spiritually-framed meditation group and the secularly-focused meditation group in comparison to the usual care control group, whose levels of depression remained constant (low quality of evidence). The influence of meditation practice on overall survival, fatigue, anxiety, quality of sleep and adverse events remained unclear, as these outcomes were not evaluated in the included trial. To estimate the effects of meditation practice for patients suffering from haematological malignancies, more high quality randomised controlled trials are needed. At present there is not enough information available on the effects of meditation in haematologically-diseased patients to draw any conclusion.",
        "gold": "We included one trial with 91 adult patients, of whom only 42 were analysed. The trial involved five one-hour meditation intervention sessions between admission and discharge of participants newly diagnosed with acute myeloid or lymphoid leukaemia. There was no information about the age of the participants included in the study. All participants in the trial were hospitalised for initial induction chemotherapy. As the abstract of the publication did not provide numbers, it is not possible to describe the results in more detail. Participants practising meditation reported better physical health and levels of depression could be decreased. Most of our pre-defined outcomes (overall survival, anxiety, fatigue, quality of sleep, and adverse events) were not reported at all. We judge the quality of the evidence for the outcomes quality of life and depression as 'very low', due to high risk of bias (only 42 out 91 participants were evaluated) and very imprecise results. There were not enough data available to determine the effectiveness of meditation practice on haematologically-diseased patients, thus the role of meditation in the treatment of haematological malignancies remains unclear. More high-quality and larger randomised controlled trials are needed to validate possible positive effects of meditation practice for haematologically-diseased patients. The evidence is up-to-date as of August, 2015."
    },
    {
        "index": "cochrane-simplification-test-9",
        "sentence": "We identified three trials involving 110 healthy children who were siblings of household contacts. The included trials varied in study quality, vaccine used, length of follow-up and outcomes measured and, as such, were not suitable for meta-analysis. We identified high or unclear risk of bias in two of the three included studies. Overall, 13 out of 56 vaccine recipients (23%) developed varicella compared with 42 out of 54 placebo (or no vaccine) recipients (78%). Of the vaccine recipients who developed varicella, the majority only had mild disease (with fewer than 50 skin lesions). In the three trials, most participants received PEP within three days following exposure; too few participants were vaccinated four to five days post-exposure to ascertain the efficacy of vaccine given more than three days after exposure. No included trial reported on adverse events following immunisation. These small trials suggest varicella vaccine administered within three days to children following household contact with a varicella case reduces infection rates and severity of cases. We identified no RCTs for adolescents or adults. Safety was not adequately addressed.",
        "gold": "The number of participants in these three trials was small and is a limitation of this review. The quality of the included studies varied, which also limits confidence in the results. There have been no trials of this type undertaken in adults, and none of the trials commented on adverse events following immunisation, such as fever or injection site reactions."
    },
    {
        "index": "cochrane-simplification-test-10",
        "sentence": "We included 12 RCTs, with 4704 participants, in this review. Eleven trials performed a total of 16 head-to-head comparisons of different prophylactic antibiotic regimens. Antibiotic prophylaxis was compared with no antibiotic prophylaxis in one trial. All the trials were at high risk of bias. With the exception of one trial in which all the participants were positive for nasal carriage of MRSA or had had previous MRSA infections, it does not appear that MRSA was tested or eradicated prior to surgery; nor does it appear that there was high prevalence of MRSA carrier status in the people undergoing surgery. There was no sufficient clinical similarity between the trials to perform a meta-analysis. The overall all-cause mortality in four trials that reported mortality was 14/1401 (1.0%) and there were no significant differences in mortality between the intervention and control groups in each of the individual comparisons. There were no antibiotic-related serious adverse events in any of the 561 people randomised to the seven different antibiotic regimens in four trials (three trials that reported mortality and one other trial). None of the trials reported quality of life, total length of hospital stay or the use of healthcare resources. Overall, 221/4032 (5.5%) people developed SSIs due to all organisms, and 46/4704 (1.0%) people developed SSIs due to MRSA. In the 15 comparisons that compared one antibiotic regimen with another, there were no significant differences in the proportion of people who developed SSIs. In the single trial that compared an antibiotic regimen with placebo, the proportion of people who developed SSIs was significantly lower in the group that received antibiotic prophylaxis with co-amoxiclav (or cefotaxime if allergic to penicillin) compared with placebo (all SSI: RR 0.26; 95% CI 0.11 to 0.65; MRSA SSI RR 0.05; 95% CI 0.00 to 0.83). In two trials that reported MRSA infections other than SSI, 19/478 (4.5%) people developed MRSA infections including SSI, chest infection and bacteraemia. There were no significant differences in the proportion of people who developed MRSA infections at any body site in these two comparisons. Prophylaxis with co-amoxiclav decreases the proportion of people developing MRSA infections compared with placebo in people without malignant disease undergoing percutaneous endoscopic gastrostomy insertion, although this may be due to decreasing overall infection thereby preventing wounds from becoming secondarily infected with MRSA. There is currently no other evidence to suggest that using a combination of multiple prophylactic antibiotics or administering prophylactic antibiotics for an increased duration is of benefit to people undergoing surgery in terms of reducing MRSA infections. Well designed RCTs assessing the clinical effectiveness of different antibiotic regimens are necessary on this topic.",
        "gold": "Antibiotics can be used individually, or combined, and administered for different durations. To identify the best antibiotic(s), or dose pattern, for preventing development of MRSA infection after surgery, we investigated studies that compared different antibiotics with each other, or with no treatment, to prevent MRSA SSIs. We included only randomised controlled trials (RCTs), and set no limits regarding language, or date, of publication, or trial size. Two review authors identified studies and extracted data independently. We identified 12 RCTs, with 4704 participants. Eleven trials compared 16 preventative (prophylactic) antibiotic treatments, and one compared antibiotic prophylaxis with no prophylaxis. Generally, MRSA status of the participants prior to surgery was not known. Four studies reported deaths (14/1401 participants): approximately 1% of participants died from any cause after surgery, but there were no significant differences between treatment groups. Four trials reported on serious antibiotic-related adverse events - there were none in 561 participants. None of the trials reported quality of life, length of hospital stay or use of healthcare resources. Overall, 221 SSIs due to any bacterium developed in 4032 people (6%), and 46 MRSA SSIs developed in 4704 people (1%). There were no significant differences in development of SSIs between the 15 comparisons of one antibiotic treatment against another. When antibiotic prophylaxis with co-amoxiclav was compared with no antibiotic prophylaxis, a significantly lower proportion of people developed SSIs after receiving co-amoxiclav (74% reduction in all SSIs, and 95% reduction in MRSA SSIs). Two trials reported that 19 participants developed MRSA infection in wounds (SSIs), chest, or bloodstream, but there were no significant differences in the proportion of people who developed them between the two comparisons. Prophylaxis with co-amoxiclav decreases the proportion of people developing MRSA infections compared with no antibiotic prophylaxis in people without cancer undergoing surgery for feeding tube insertion into the stomach using endoscopy, although this may be due to decreasing overall infection thereby preventing wounds from becoming secondarily infected with MRSA. There is currently no other evidence that either a combination of prophylactic antibiotics, or increased duration of antibiotic treatment, benefits people undergoing surgery in terms of reducing MRSA infections. Well-designed RCTs are necessary to assess different antibiotic treatments for preventing MRSA infections after surgery."
    },
    {
        "index": "cochrane-simplification-test-11",
        "sentence": "We included two trials (116 women) comparing planned home versus hospital management for PPROM. Overall, the number of included women in each trial was too small to allow adequate assessment of pre-specified outcomes. Investigators used strict inclusion criteria and in both studies relatively few of the women presenting with PPROM were eligible for inclusion. Women were monitored for 48 to 72 hours before randomisation. Perinatal mortality was reported in one trial and there was insufficient evidence to determine whether it differed between the two groups (risk ratio (RR) 1.93, 95% confidence interval (CI) 0.19 to 20.05).\u00a0 There was no evidence of differences between groups for serious neonatal morbidity, chorioamnionitis, gestational age at delivery, birthweight and admission to neonatal intensive care. There was no information on serious maternal morbidity or mortality. There was some evidence that women managed in hospital were more likely to be delivered by caesarean section (RR (random-effects) 0.28, 95% CI 0.07 to 1.15). However, results should be interpreted cautiously as there is moderate heterogeneity for this outcome (I\u00b2 = 35%). Mothers randomised to care at home spent approximately 10 fewer days as inpatients (mean difference -9.60, 95% CI -14.59 to -4.61) and were more satisfied with their care. Furthermore, home care was associated with reduced costs. The review included two relatively small studies that did not have sufficient statistical power to detect meaningful differences between groups. Future large and adequately powered randomised controlled trials are required to measure differences between groups for relevant pre-specified outcomes. Special attention should be given to the assessment of maternal satisfaction with care and cost analysis as they will have social and economic implications in both developed and developing countries.",
        "gold": "We included two randomised controlled studies with 116 women in the review. These studies compared planned home versus hospital management for women with preterm, prelabour rupture of the membranes (PPROM). In both studies there were strict criteria for deciding whether women could be included; for example, women had to live within a certain distance of emergency facilities, and there had to be no signs that mothers and babies had infection or other problems. There was a period of monitoring in hospital for women in both groups. Results suggested that there were few differences in mothers' and babies' health for women cared for at home or in hospital including infant death, serious illness, or admission to intensive care baby units. There was some evidence that women managed in hospital were more likely to be delivered by caesarean section. Women cared for at home were likely to spend less time in hospital (spending approximately 10 fewer days as inpatients) and were more satisfied with their care. In addition, home care was associated with reduced costs. Overall, the number of women included in the two studies was too small to allow adequate assessment of outcomes."
    },
    {
        "index": "cochrane-simplification-test-12",
        "sentence": "The two methods of skin closure for caesarean that have been most often compared are non-absorbable staples and absorbable subcutaneous sutures. Compared with absorbable subcutaneous sutures, non-absorbable staples are associated with similar incidences of wound infection. Other important secondary outcomes, such as wound complications, were also similar between the groups in women with Pfannenstiel incisions. However, it is important to note, that for both of these outcomes (wound infection and wound complication), staples may have a differential effect depending on the type of skin incision, i.e., Pfannenstiel or vertical. Compared with absorbable subcutaneous sutures, non-absorbable staples are associated with an increased risk of skin separation, and therefore, reclosure. However, skin separation was variably defined across trials, and most staples were removed before four days postpartum. There is currently no conclusive evidence about how the skin should be closed after caesarean section. Staples are associated with similar outcomes in terms of wound infection, pain and cosmesis compared with sutures, and these two are the most commonly studied methods for skin closure after caesarean section. If staples are removed on day three, there is an increased incidence of skin separation and the need for reclosure compared with absorbable sutures.",
        "gold": "We identified 19 randomized controlled trials and included 11, but only eight contributed data. The most commonly studied methods of skin closure were non-absorbable staples compared with absorbable subcutaneous sutures. Staples were associated with similar outcomes in terms of wound infection, pain and appearance compared with sutures. Non-absorbable staples had an increased risk of skin separation and, therefore, reclosure. Skin separation was defined differently across trials and removal of staples varied from about day three to day seven postoperatively. There is not enough evidence from the included studies to say which method of closing the caesarean skin incision is superior. Too few trials compared different kinds of sutures. The use of prophylactic antibiotics to reduce infection was not reported in most trials."
    },
    {
        "index": "cochrane-simplification-test-13",
        "sentence": "We identified 11 RCTs with a total of 821 participants, two trials awaiting classification and one ongoing trial. Seven trials examined a green tea intervention and four examined a black tea intervention. Dosage and form of both green and black tea differed between trials. The ongoing trial is examining the effects of green tea powder capsules. No studies reported cardiovascular events. Black tea was found to produce statistically significant reductions in low-density lipoprotein (LDL) cholesterol (mean difference (MD) -0.43 mmol/L, 95% confidence interval (CI) -0.56 to -0.31) and blood pressure (systolic blood pressure (SBP): MD -1.85 mmHg, 95% CI -3.21 to -0.48. Diastolic blood pressure (DBP): MD -1.27 mmHg, 95% CI -3.06 to 0.53) over six months, stable to sensitivity analysis, but only a small number of trials contributed to each analysis and studies were at risk of bias. Green tea was also found to produce statistically significant reductions in total cholesterol (MD -0.62 mmol/L, 95% CI -0.77 to -0.46), LDL cholesterol (MD -0.64 mmol/L, 95% CI -0.77 to -0.52) and blood pressure (SBP: MD -3.18 mmHg, 95% CI -5.25 to -1.11; DBP: MD -3.42, 95% CI -4.54 to -2.30), but only a small number of studies contributed to each analysis, and results were not stable to sensitivity analysis. When both tea types were analysed together they showed favourable effects on LDL cholesterol (MD -0.48 mmol/L, 95% CI -0.61 to -0.35) and blood pressure (SBP: MD -2.25 mmHg, 95% CI -3.39 to -1.11; DBP: MD -2.81 mmHg, 95% CI -3.77 to -1.86). Adverse events were measured in five trials and included a diagnosis of prostate cancer, hospitalisation for influenza, appendicitis and retinal detachment but these are unlikely to be directly attributable to the intervention. There are very few long-term studies to date examining green or black tea for the primary prevention of CVD. The limited evidence suggests that tea has favourable effects on CVD risk factors, but due to the small number of trials contributing to each analysis the results should be treated with some caution and further high quality trials with longer-term follow-up are needed to confirm this.",
        "gold": "This review assessed the effectiveness of green tea, black tea or black/green tea extracts in healthy adults and those at high risk of CVD. We found 11 randomised controlled trials, four of which examined black tea interventions and seven examined green tea interventions. There were variations in the dosage and form (drink, tablets or capsules) of the black and green tea interventions, and the duration of the interventions ranged from three months to six months. Adverse events were reported in five of the included trials. These included a diagnosis of prostate cancer, hospitalisation for influenza, appendicitis and retinal detachment; these are unlikely to be associated with the intervention. The results showed black and green tea to have a beneficial effect on lipid levels and blood pressure, but these results were based on only a small number of trials that were at risk of bias. Analysis conducted over both tea types showed beneficial effects of tea on LDL-cholesterol and blood pressure but again this was based on only a few trials that were at risk of bias. To date the small number of studies included suggest some benefits of green and black tea on blood pressure and lipid levels but more longer-term trials at low risk of bias are needed to confirm this."
    },
    {
        "index": "cochrane-simplification-test-14",
        "sentence": "Two small trials recruiting 23 participants met the inclusion criteria for the review. Participants may have been suffering from comorbid lung disease. No data on oral steroid consumption were reported. No significant differences were observed in the studies for FEV1, FVC, PaO2 and symptoms. One study reported a statistically significant difference in SGaw, but the clinical importance of this is uncertain. Due to concerns over the small sample sizes and methodological shortcomings in terms of inadequate washout in one study, and methods used in outcome assessment for both studies, the findings of the studies are not generalisable to the issue of steroid tapering. An update search conducted in August 2010 did not identify any new studies for consideration in the review. Currently there is a clear lack of evidence to support the use of azathioprine in the treatment of chronic asthma as a steroid sparing-agent. Large, long-term studies with pre-defined steroid reducing protocols are required before recommendations for clinical practice can be made.",
        "gold": "The review found two small studies which did not provide adequate evidence as to whether azathioprine could be offered to reduce oral steroid treatment. There is a need for well-designed trials addressing this question before recommendations can be made."
    },
    {
        "index": "cochrane-simplification-test-15",
        "sentence": "For this update we identified a total of 56 studies (4068 participants) for inclusion (28 from the original search and 28 from the updated search), with the majority carried out in participants with breast cancer (28 studies). A meta-analysis of all fatigue data, incorporating 38 comparisons, provided data for 1461 participants who received an exercise intervention and 1187 control participants. At the end of the intervention period exercise was seen to be statistically more effective than the control intervention (standardised mean difference (SMD) -0.27, 95% confidence interval (CI) -0.37 to -0.17). Benefits of exercise on fatigue were observed for interventions delivered during or post-adjuvant cancer therapy. In relation to diagnosis, we identified benefits of exercise on fatigue for breast and prostate cancer but not for those with haematological malignancies. Finally, aerobic exercise significantly reduced fatigue but resistance training and alternative forms of exercise failed to reach significance. The findings of the updated review have enabled a more precise conclusion to be made in that aerobic exercise can be regarded as beneficial for individuals with cancer-related fatigue during and post-cancer therapy, specifically those with solid tumours. Further research is required to determine the optimal type, intensity and timing of an exercise intervention.",
        "gold": "A number of studies have been carried out to investigate the effects of exercise both during and after treatment. The current review was carried out to evaluate the effect of physical exercise on fatigue related to cancer. Fifty-six studies, involving a total of 4068 participants, were included in this review. Results suggest that physical exercise such as aerobic walking and aerobic cycling can help to reduce fatigue both during and after treatment for cancer. The benefits of exercise on fatigue were observed specifically for people with breast cancer and prostate cancer."
    },
    {
        "index": "cochrane-simplification-test-16",
        "sentence": "We screened 1796 records and identified five eligible trials in total i.e. one trial could be added on the previous review. These trials included only adults (16 to 65 years of age). We included all five trials with 3427 people in the meta-analyses: the HD9 and HD14 trials were co-ordinated in Germany, the HD2000 and GSM-HD trials were performed in Italy and the EORTC 20012 was conducted in Belgium. The overall risk of performance and detection bias was low for overall survival (OS), but was high for other outcomes, as therapy blinding was not feasible. The remaining 'Risk of bias' domains were low and unclear. All trials reported results for OS and progression-free survival (PFS). In contrast to the our first published review (2011) the addition of results from the EORTC 20012 BEACOPP escalated increases OS (3142 participants; HR 0.74 (95% confidence interval (CI) 0.57 to 0.97; high-quality evidence). This means that only 90 (70 to 117) patients will die after five years in the BEACOPP escalated arm compared to 120 in the ABVD arm. This survival advantage is also reflected in an increased PFS with BEACOPP escalated (3142 participants; HR 0.54 (95% CI 0.45 to 0.64); moderate-quality evidence), meaning that after five years only 144 (121 to 168) patients will experience a progress, relapse or death in the BEACOPP escalated arm compared to 250 in the ABVD arm. There is no evidence for a difference for treatment-related mortality (2700 participants, RR 2.15 (95% CI = 0.93 to 4.95), low-quality evidence). Although the occurrence of MDS or AML may increase with BEACOPP escalated (3332 participants, RR 3.90 (95% CI 1.36 to 11.21); low-quality evidence)), there is no evidence for a difference between both regimens for overall secondary malignancies (3332 participants, RR 1.00 (95% CI 0.68 to 1.48), low-quality evidence). However, the observation time of the studies included in the review is too short to be expected to demonstrate differences with respect to second solid tumours which would not be expected to show significance until around 15 years after treatment. We are very uncertain how many female patients will be infertile due to chemotherapy and which arm might be favoured (106 participants, RR 1.37 (95% CI 0.83 to 2.26), very low-quality evidence). This is a very small sample, and the age of the patients was not detailed. No analysis of male fertility was provided. Five trials reported adverse events and the analysis shows that the escalated BEACOPP regimens probably causes more haematological toxicities WHO grade III or IV ((anaemia: 2425 participants, RR 10.67 (95% CI 7.14 to 15.93); neutropenia: 519 participants, RR 1.80 (95% CI 1.52 to 2.13); thrombocytopenia: 2425 participants, RR 18.12 (95% CI 11.77 to 27.92); infections: 2425 participants, RR 3.73 (95% CI 2.58 to 5.38), all low-quality evidence). Only one trial (EORTC 20012) planned to assess quality of life, however, no results were reported. This meta-analysis provides moderate- to high-quality evidence that adult patients between 16 and 60 years of age with early unfavourable and advanced stage HL benefit regarding OS and PFS from first-line chemotherapy including escalated BEACOPP. The proven benefit in OS for patients with advanced HL is a new finding of this updated review due to the inclusion of the results from the EORTC 20012 trial. Furthermore, there is only low-quality evidence of a difference in the total number of secondary malignancies, as the follow-up period might be too short to detect meaningful differences. Low-quality evidence also suggests that people treated with escalated BEACOPP may have a higher risk to develop secondary AML or MDS. Due to the availability of only very low-quality evidence available, we are unable to come to a conclusion in terms of infertility. This review does for the first time suggest a survival benefit. However, it is clear from this review that BEACOPP escalated may be more toxic that ABVD, and very important long-term side effects of second malignancies and infertility have not been sufficiently analysed yet.",
        "gold": "We found five eligible trials by the date of this updated review (search date March 2017). These trials included 3427 patients adult patients (16 to 65 years of age). For this updated review there are new data available resulting in a benefit in terms of overall survival (OS) for people with early unfavourable and advanced HL receiving BEACOPP escalated for first-line treatment. Furthermore, the analysis shows a better chance of avoiding recurrence of the tumour in patients who received chemotherapy including BEACOPP escalated. We analysed the following harms potentially caused by both regimens. There is no evidence for a difference for treatment-related mortality. There is evidence for a higher risk of secondary acute myeloid leukaemia (AML) or myelodysplastic syndromes (MDS) in patients receiving BEACOPP escalated, but the total number of secondary malignancies does not show evidence for a difference between both treatment groups. However, the observation time of the studies included in the review is too short to be expected to demonstrate differences with respect to second solid tumours. We are very uncertain how many female patients will be infertile due to chemotherapy and which arm might be favoured, as the evaluated sample is very small. No data for male patients and risk for infertility was provided. Treatment with BEACOPP escalated caused a higher risk of adverse events such as anaemia, neutropenia, thrombocytopenia and infections. Quality of life was not reported by any of the included trials. One trial stated it would assess quality of life, however, there were no results reported. We assessed the quality of the evidence as high relating to overall survival, as moderate for progression-free survival and as low for secondary AML or MDS, secondary malignancies and treatment-related mortality and adverse events. The quality of evidence is very low for infertility."
    },
    {
        "index": "cochrane-simplification-test-17",
        "sentence": "Fifteen RCTs including 1835 cancer patients met the inclusion criteria and because of multiple arms studies we included 19 evaluations. We judged six studies to have a high risk of bias and nine to have a low risk of bias. All included studies were conducted in high income countries and most studies were aimed at breast cancer patients (seven trials) or prostate cancer patients (two trials). Two studies involved psycho-educational interventions including patient education and teaching self-care behaviours. Results indicated low quality evidence of similar RTW rates for psycho-educational interventions compared to care as usual (RR 1.09, 95% CI 0.88 to 1.35, n = 260 patients) and low quality evidence that there is no difference in the effect of psycho-educational interventions compared to care as usual on quality of life (standardised mean difference (SMD) 0.05, 95% CI -0.2 to 0.3, n = 260 patients). We did not find any studies on vocational interventions. In one study breast cancer patients were offered a physical training programme. Low quality evidence suggested that physical training was not more effective than care as usual in improving RTW (RR 1.20, 95% CI 0.32 to 4.54, n = 28 patients) or quality of life (SMD -0.37, 95% CI -0.99 to 0.25, n = 41 patients). Seven RCTs assessed the effects of a medical intervention on RTW. In all studies a less radical or functioning conserving medical intervention was compared with a more radical treatment. We found low quality evidence that less radical, functioning conserving approaches had similar RTW rates as more radical treatments (RR 1.04, 95% CI 0.96 to 1.09, n = 1097 patients) and moderate quality evidence of no differences in quality of life outcomes (SMD 0.10, 95% CI -0.04 to 0.23, n = 1028 patients). Five RCTs involved multidisciplinary interventions in which vocational counselling, patient education, patient counselling, biofeedback-assisted behavioral training and/or physical exercises were combined. Moderate quality evidence showed that multidisciplinary interventions involving physical, psycho-educational and/or vocational components led to higher RTW rates than care as usual (RR 1.11, 95% CI 1.03 to 1.16, n = 450 patients). We found no differences in the effect of multidisciplinary interventions compared to care as usual on quality of life outcomes (SMD 0.03, 95% CI -0.20 to 0.25, n = 316 patients). We found moderate quality evidence that multidisciplinary interventions enhance the RTW of patients with cancer.",
        "gold": "The search date was 25 March 2014. Fifteen randomised controlled trials including 1835 cancer patients met the inclusion criteria. We found four types of interventions. In the first, psycho-educational interventions, participants learned about physical side effects, stress and coping and they took part in group discussions. In the second type of physical intervention participants took part in exercises such as walking. In the third type of intervention, participants received medical interventions ranging from cancer drugs to surgery. The fourth kind concerned multidisciplinary interventions in which vocational counselling, patient education, patient counselling, biofeedback-assisted behavioral training and/or physical exercises were combined.We did not find any studies on vocational interventions aimed at work-related issues. Key results Results suggest that multidisciplinary interventions involving physical, psycho-educational and/or vocational components led to more cancer patients returning to work than when they received care as usual. Quality of life was similar. When studies compared psycho-educational, physical and medical interventions with care as usual they found that similar numbers of people returned to work in all groups. Quality of the evidence We found low quality evidence of similar return-to-work rates for psycho-educational interventions compared to care as usual. We also found low quality evidence showing that physical training was not more effective than care as usual in improving return-to-work. We also found low quality evidence that less radical cancer treatments had similar return-to-work rates as more radical treatments. Moderate quality evidence showed multidisciplinary interventions involving physical, psycho-educational and/or vocational components led to higher return-to-work rates than care as usual."
    },
    {
        "index": "cochrane-simplification-test-18",
        "sentence": "We included no new trials in this update. We included four trials involving more than 13,000 women which were conducted in the UK and Ireland and included women in labour. Three trials were funded by the hospitals where the trials took place and one trial was funded by the Scottish government. No declarations of interest were made in two trials; the remaining two trials did not mention declarations of interest. Overall, the studies were assessed as low risk of bias. Results reported in the 2012 review remain unchanged. Although not statistically significant using a strict P < 0.05 criterion, data were consistent with women allocated to admission CTG having, on average, a higher probability of an increase in incidence of caesarean section than women allocated to intermittent auscultation (risk ratio (RR) 1.20, 95% confidence interval (CI) 1.00 to 1.44, 4 trials, 11,338 women, I\u00b2 = 0%, moderate quality evidence). There was no clear difference in the average treatment effect across included trials between women allocated to admission CTG and women allocated to intermittent auscultation in instrumental vaginal birth (RR 1.10, 95% CI 0.95 to 1.27, 4 trials, 11,338 women, I\u00b2 = 38%, low quality evidence) and perinatal mortality rate (RR 1.01, 95% CI 0.30 to 3.47, 4 trials, 11,339 infants, I\u00b2 = 0%, moderate quality evidence). Women allocated to admission CTG had, on average, higher rates of continuous electronic fetal monitoring during labour (RR 1.30, 95% CI 1.14 to 1.48, 3 trials, 10,753 women, I\u00b2 = 79%, low quality evidence) and fetal blood sampling (RR 1.28, 95% CI 1.13 to 1.45, 3 trials, 10,757 women, I\u00b2 = 0%) than women allocated to intermittent auscultation. There were no differences between groups in other secondary outcome measures including incidence and severity of hypoxic ischaemic encephalopathy (incidence only reported) (RR 1.19, 95% CI 0.37 to 3.90; 2367 infants; 1 trial; very low quality evidence) and incidence of seizures in the neonatal period (RR 0.72, 95% CI 0.32 to 1.61; 8056 infants; 1 trial; low quality evidence). There were no data reported for severe neurodevelopmental disability assessed at greater than, or equal to, 12 months of age. Contrary to continued use in some clinical areas, we found no evidence of benefit for the use of the admission CTG for low-risk women on admission in labour. Furthermore, the probability is that admission CTG increases the caesarean section rate by approximately 20%. The data lacked power to detect possible important differences in perinatal mortality. However, it is unlikely that any trial, or meta-analysis, will be adequately powered to detect such differences. The findings of this review support recommendations that the admission CTG not be used for women who are low risk on admission in labour. Women should be informed that admission CTG is likely associated with an increase in the incidence of caesarean section without evidence of benefit. Evidence quality ranged from moderate to very low, with downgrading decisions based on imprecision, inconsistency and a lack of blinding for participants and personnel. All four included trials were conducted in developed Western European countries. One additional study is ongoing. The usefulness of the findings of this review for developing countries will depend on FHR monitoring practices. However, an absence of benefit and likely harm associated with admission CTG will have relevance for countries where questions are being asked about the role of the admission CTG. Future studies evaluating the effects of the admission CTG should consider including women admitted with signs of labour and before a formal diagnosis of labour. This would include a cohort of women currently having admission CTGs and not included in current trials.",
        "gold": "We compared the admission CTG with intermittent auscultation of the FHR performed on the woman's admission to the labour ward. We searched for evidence to 30 November 2016 but found no new studies for this updated review (previously published in 2012). This review includes four studies and there is one study that is not yet complete. The included studies (carried out in the UK and Ireland) involved more than 13,000 women with low-risk pregnancies. Three trials were funded by the hospitals were the trials took place and one trial was funded by the Scottish government. Women allocated to admission CTG were probably more likely to have a caesarean section than women allocated to intermittent auscultation (moderate quality evidence). There was no difference in the number of instrumental vaginal births (low quality evidence) or in numbers of babies who died during or shortly after labour (moderate quality evidence) between women in the two groups. Admission CTG was associated with an increase in the use of continuous EFM (with an electrode placed on the baby\u2019s scalp) (low quality evidence) and fetal blood sampling (a small blood sample taken from a baby's scalp) during labour. There were no differences in other outcomes measured such as artificial rupture of the membranes, augmentation of labour, use of an epidural, damage to the baby's brain due to lack of oxygen (very low quality evidence), or the baby having fits or seizures just after birth (low quality evidence). No studies reported if the babies developed any severe problems in brain or central nervous system growth and development after one year of age. Although many hospitals carry out CTGs on women when they are admitted to hospital in labour, we found no evidence that this benefits women with low-risk pregnancies. We found that admission CTGs may increase numbers of women having a caesarean section by about 20%. The included studies did not include enough women to show if admission CTGs or intermittent auscultation were better at keeping babies safe. However, studies to show which is better at keeping babies safe would have to be very large. Based on this review, low-risk pregnant women who have an admission CTG could be more likely to have a caesarean section. The benefits to these women of having an admission CTG are not certain. All of the included studies took place in developed Western European countries. The review findings might not be useful to people in very different countries or where different ways of FHR monitoring are used. However, countries that use admission CTGs should start to question why, because there are not clear benefits to using admission CTGs, and they could be causing women harm by making them more likely to have a caesarean section."
    },
    {
        "index": "cochrane-simplification-test-19",
        "sentence": "We included 32 studies in this review. Seventeen studies randomised women (total 3666), three randomised cycles (total 1018) and twelve randomised oocytes (over 15,230). It was not possible to pool any of the data because each study compared different culture media. Only seven studies reported live birth or ongoing pregnancy. Four of these studies found no evidence of a difference between the media compared, for either day three or day five embryo transfer. The data from the fifth study did not appear reliable. Six studies reported clinical pregnancy rate. One of these found a difference between the media compared, suggesting that for cleavage-stage embryo transfer, Quinn's Advantage was associated with higher clinical pregnancy rates than G5 (odds ratio (OR) 1.56; 95% confidence interval (CI) 1.12 to 2.16; 692 women). This study was available only as an abstract and the quality of the evidence was low. With regards to adverse effects, three studies reported multiple pregnancies and six studies reported miscarriage. None of them found any evidence of a difference between the culture media used. None of the studies reported on the health of offspring. Most studies (22/32) failed to report their source of funding and none described their methodology in adequate detail. The overall quality of the evidence was rated as very low for nearly all comparisons, the main limitations being imprecision and poor reporting of study methods. An optimal embryo culture medium is important for embryonic development and subsequently the success of IVF or ICSI treatment. There has been much controversy about the most appropriate embryo culture medium. Numerous studies have been performed, but no two studies compared the same culture media and none of them found any evidence of a difference between the culture media used. We conclude that there is insufficient evidence to support or refute the use of any specific culture medium. Properly designed and executed randomised trials are necessary.",
        "gold": "The evidence is current to March 2015. We included 32 randomised controlled trials of a wide variety of different commercially available culture media in women undergoing IVF or ICSI. Sixteen studies randomised women (total 3666), three randomised cycles (total 1018) and twelve randomised oocytes (over 15,230). Most studies (22/32) failed to report their source of funding. No two studies compared the same culture media. Only seven studies reported our primary outcome of live birth or ongoing pregnancy, and they found no good evidence of a difference between the media compared. A single study found low-quality evidence that for day three embryo transfer, Quinn's Advantage may be associated with higher rates than G5, but this study was available only as an abstract and the methods used were not clearly reported. With regard to adverse effects, three studies reported multiple pregnancies and six studies reported miscarriage. None of them found any evidence of a difference between the culture media used. None of the studies reported on the health of offspring. We conclude that there is insufficient evidence to support or refute the use of any specific culture medium. Properly designed and executed randomised trials are necessary. There was very low-quality evidence for nearly all comparisons, the main limitations being imprecision and poor reporting of study methods."
    },
    {
        "index": "cochrane-simplification-test-20",
        "sentence": "The search strategies identified 2847 citations overall. A total of 30 citations appeared relevant however there were three duplicates which left 27 articles for further review. Articles reporting the same primary data accounted for 6 of the publications Brown 1997; Brown 1998; Brown 1999; Brown 2000; Hack 2000; Hack 2003 which left 23 original papers to be reviewed for inclusion. Of these, none met the inclusion criteria. Data extraction and assessment of methodological quality was therefore not possible. The review question remains unanswered as there were no randomised trials of methods of communicating a diagnosis of breast cancer to women. The authors have considered the possible reasons for the lack of research studies in this area and have considered that it is perhaps unethical to randomise women at such a vulnerable time such as waiting for a diagnosis. The design of ethically sensitive research to examine this topic needs to be explored to inform future practice. As some papers reviewed by the authors related to the first consultation visit, where treatment options are discussed, perhaps a review which focused on the methods of communication at the first consultation visit would provide more reliable evidence for the effectiveness of methods of communication and overcome the ethical dilemmas previously mentioned.",
        "gold": "The present systematic review set out to assess the effectiveness of various methods of communicating a first diagnosis of confirmed breast cancer. The review was particularly interested in how this would impact on what the patient remembered, the satisfaction with the information received, the coping strategies used as a result of the information given and the impact of receiving the information on the patient's quality of life. The review authors made a thorough search of the medical literature looking for controlled trials in which women receiving a first diagnosis of breast cancer were randomised to the intervention group. They retrieved 23 original reports of trials for further review but ultimately no trial could be included. A number of the trials focused on communication at the first treatment consultation rather than the method of delivering the diagnosis. In an area that is ethically sensitive, the authors suggest that a review which focuses on the various methods of communication at the first consultation visit may provide useful information as to which methods are more effective and beneficial for this patient group."
    },
    {
        "index": "cochrane-simplification-test-21",
        "sentence": "We included two new papers, one of which was an update of a previously included study. Therefore, a total of 17 RCTs with 1006 randomised participants met the inclusion criteria, with the one new study contributing an additional 113 participants. There was a significant reduction in reports of chest pain in the first three months following the intervention: random-effects relative risk = 0.70 (95% CI 0.53 to 0.92). This was maintained from three to nine months afterwards: relative risk 0.59 (95% CI 0.45 to 0.76). There was also a significant increase in the number of chest pain-free days up to three months following the intervention: mean difference (MD) 3.00 (95% CI 0.23 to 5.77). This was associated with reduced chest pain frequency (random-effects MD -2.26, 95% CI -4.41 to -0.12) but there was no evidence of effect of treatment on chest pain frequency from three to twelve months (random-effects MD -0.81, 95% CI -2.35 to 0.74). There was no effect on severity (random-effects MD -4.64 (95% CI -12.18 to 2.89) up to three months after the intervention. Due to the nature of the main interventions of interest, it was impossible to blind the therapists as to whether the participant was in the intervention or control arm. In addition, in three studies the blinding of participants was expressly forbidden by the local ethics committee because of issues in obtaining fully informed consent . For this reason, all studies had a high risk of performance bias. In addition, three studies were thought to have a high risk of outcome bias. In general, there was a low risk of bias in the other domains. However, there was high heterogeneity and caution is required in interpreting these results. The wide variability in secondary outcome measures made it difficult to integrate findings from studies. This Cochrane review suggests a modest to moderate benefit for psychological interventions, particularly those using a cognitive-behavioural framework, which was largely restricted to the first three months after the intervention. Hypnotherapy is also a possible alternative. However, these conclusions are limited by high heterogeneity in many of the results and low numbers of participants in individual studies. The evidence for other brief interventions was less clear. Further RCTs of psychological interventions for NSCP with follow-up periods of at least 12 months are needed.",
        "gold": "This Cochrane review included all studies of psychotherapy for non-cardiac chest pain. Seventeen trials met the inclusion criteria, and included a total of 1006 participants. The review found that cognitive-behavioural treatments are probably effective (in terms of reduced chest pain frequency) in the short term, for the treatment of non-cardiac related chest pain. No adverse effects of the psychotherapy were found. Hypnotherapy is also a possible alternative. A limitation of this review is the high variability of the studies included, reflected in a wide range of outcome measures, although there was an overall fairly low risk of bias."
    },
    {
        "index": "cochrane-simplification-test-22",
        "sentence": "We identified 30 trials with a total of 4344 participants randomised, with 17 different drugs or treatment comparisons. The following antihistamines and mast cell stabilisers were evaluated in at least one RCT: nedocromil sodium or sodium cromoglycate, olopatadine, ketotifen, azelastine, emedastine, levocabastine (or levocabastine), mequitazine, bepotastine besilate, combination of antazoline and tetryzoline, combination of levocabastine and pemirolast potassium. The most common comparison was azelastine versus placebo (nine studies). We observed a large variability in reporting outcomes. The quality of the studies and reporting was variable, but overall the risk of bias was low. Trials evaluated only short-term effects, with a range of treatment of one to eight weeks. Meta-analysis was only possible in one comparison (olopatadine versus ketotifen). There was some evidence to support that topical antihistamines and mast cell stabilisers reduce symptoms and signs of seasonal allergic conjunctivitis when compared with placebo. There were no reported serious adverse events related to the use of topical antihistamine and mast cell stabilisers treatment. It seems that all reported topical antihistamines and mast cell stabilisers reduce symptoms and signs of seasonal allergic conjunctivitis when compared with placebo in the short term. However, there is no long-term data on their efficacy. Direct comparisons of different antihistamines and mast cell stabilisers need to be interpreted with caution. Overall, topical antihistamines and mast cell stabilisers appear to be safe and well tolerated. We observed a large variability in outcomes reported. Poor quality of reporting challenged the synthesis of evidence.",
        "gold": "The evidence is current to July 2014. Among the 30 studies reviewed there were 17 different comparisons, including 4344 participants ranging in age between 4 and 85 years. The duration of treatment ranged from one to eight weeks. Ten out of 30 studies were funded by the drug manufacturer (8 totally and 2 partially funded); 20 studies did not report any source of funding. There was inconsistency in the way the effect of treatment was measured and reported. Overall risk of bias was low. Topical antihistamines and mast cell stabilisers, alone or in combination, are safe and effective for reducing symptoms of seasonal and perennial allergic conjunctivitis. We found insufficient evidence to discern which topical antihistamines and mast cell stabilisers are the most effective."
    },
    {
        "index": "cochrane-simplification-test-23",
        "sentence": "Two studies met all of the eligibility criteria for inclusion within the review and a third was identified as ongoing. The two included studies employed multi-component community-based interventions tailored to the specific cultural aspects of the population and were based in Native American populations (1505 subjects in total). No difference was observed in weekly smoking at 42 months follow-up in the one study assessing this outcome (skills-community group versus control: risk ratio [RR] 0.95, 95% CI 0.78 to 1.14; skills-only group versus control: RR 0.86, 95% CI 0.71 to 1.05). For smokeless tobacco use, no difference was found between the skills-community arm and the control group at 42 weeks (RR 0.93, 95% CI 0.67 to 1.30), though a significant difference was observed between the skills-only arm and the control group (RR 0.57, 95% CI 0.39 to 0.85). Whilst the second study found positive changes for tobacco use in the intervention arm at post test (p < 0.05), this was not maintained at six month follow-up (change score -0.11 for intervention and 0.07 for control). Both studies were rated as high or unclear risk of bias in seven or more domains (out of a total of 10). Based on the available evidence, a conclusion cannot be drawn as to the efficacy of tobacco prevention initiatives tailored for Indigenous youth. This review highlights the paucity of data and the need for more research in this area. Smoking prevalence in Indigenous youth is twice that of the non-Indigenous population, with tobacco experimentation commencing at an early age. As such, a significant health disparity exists where Indigenous populations, a minority, are over-represented in the burden of smoking-related morbidity and mortality. Methodologically rigorous trials are needed to investigate interventions aimed at preventing the uptake of tobacco use amongst Indigenous youth and to assist in bridging the gap between tobacco-related health disparities in Indigenous and non-Indigenous populations.",
        "gold": "This review found that there is not enough published research evaluating programmes aiming to prevent Indigenous youth from starting to use tobacco. Information from the two included studies in this review (1505 participants in total, in Native American communities) does not allow a conclusion to be drawn as to whether tobacco prevention programmes in Indigenous populations prevent Indigenous youth from smoking or using smokeless tobacco. The review highlights the absence of data and need for more research."
    },
    {
        "index": "cochrane-simplification-test-24",
        "sentence": "Out of six relevant reports identified by the search strategy, one trial involving 72 women with sickle cell anaemia (HbSS) met our inclusion criteria. The trial was at unclear risk of bias. Overall, there were few events for most of the reported outcomes and the results were generally imprecise. The included trial reported no maternal mortality occurring in women who received either prophylactic or selective blood transfusion. Very low-quality evidence indicated no clear differences in maternal mortality, perinatal mortality (risk ratio (RR) 2.85, 95% confidence interval (CI) 0.61 to 13.22; very low-quality evidence) or markers of severe maternal morbidity (pulmonary embolism (no events); congestive cardiac failure (RR 1.00, 95% CI 0.07 to 15.38; very low-quality evidence); acute chest syndrome (RR 0.67, 95% CI 0.12 to 3.75)) between the treatment groups (prophylactic blood transfusion versus selective blood transfusion). Low-quality evidence indicated that prophylactic blood transfusion reduced the risk of pain crisis compared with selective blood transfusion (RR 0.28, 95% CI 0.12 to 0.67, one trial, 72 women; low-quality evidence), and no differences in the occurrence of acute splenic sequestration (RR 0.33, 95% CI 0.01 to 7.92; low-quality evidence), haemolytic crises (RR 0.33, 95% CI 0.04 to 3.06) or delayed blood transfusion reaction (RR 2.00, 95% CI 0.54 to 7.39; very low-quality evidence) between the comparison groups. Other relevant maternal outcomes pre-specified for this review such as cumulative duration of hospital stay, postpartum haemorrhage and iron overload, and infant outcomes, admission to neonatal intensive care unit (NICU) and haemolytic disease of the newborn, were not reported by the trial. Evidence from one small trial of very low quality suggests that prophylactic blood transfusion to pregnant women with sickle cell anaemia (HbSS) confers no clear clinical benefits when compared with selective transfusion. Currently, there is no evidence from randomised or quasi-randomised trials to provide reliable advice on the optimal blood transfusion policy for women with other variants of sickle cell disease (i.e. HbSC and HbS\u03b2Thal). The available data and quality of evidence on this subject are insufficient to advocate for a change in existing clinical practice and policy.",
        "gold": "We searched for evidence on 30 May 2016 and identified one controlled trial, with an unclear risk of bias, that randomised 72 women with sickle cell anaemia (haemoglobin SS) before 28 weeks of gestation to one of the two blood transfusion policies. The trial indicated no difference in severe ill health and death of the mother or newborn. There was no difference in the risk of delayed blood transfusion reaction. The trial suggested giving blood at frequent intervals reduced the risk of pain crisis, with a large degree of uncertainty about the size of the effect, compared with giving blood only when medically indicated. Blood transfusion was delivered at a ratio of four to one for prophylactic versus selective blood transfusion, respectively. Overall, the quality of evidence for outcomes that are important to the woman is very low. The available evidence on this subject is insufficient to advocate for a change in clinical practice and policy. More research needs to be conducted."
    },
    {
        "index": "cochrane-simplification-test-25",
        "sentence": "We identified 67 randomised clinical trials involving a total of 6197 participants. All the trials were at high risk of bias. A total of 5771 participants from 64 trials provided data for one or more outcomes included in this review. There was no evidence of differences in most of the comparisons, and where there was, these differences were in single trials, mostly of small sample size. We summarise only the evidence that was available in more than one trial below. Of the primary outcomes, the only one with evidence of a difference from more than one trial under the pair-wise comparison was in the number of adverse events (complications), which was higher with radiofrequency dissecting sealer than with the clamp-crush method (rate ratio 1.85, 95% CrI 1.07 to 3.26; 250 participants; 3 studies; very low-quality evidence). Among the secondary outcomes, the only differences we found from more than one trial under the pair-wise comparison were the following: blood transfusion (proportion) was higher in the low central venous pressure group than in the acute normovolemic haemodilution plus low central venous pressure group (OR 3.19, 95% CrI 1.56 to 6.95; 208 participants; 2 studies; low-quality evidence); blood transfusion quantity (red blood cells) was lower in the fibrin sealant group than in the control (MD \u22120.53 units, 95% CrI \u22121.00 to \u22120.07; 122 participants; 2; very low-quality evidence); blood transfusion quantity (fresh frozen plasma) was higher in the oxidised cellulose group than in the fibrin sealant group (MD 0.53 units, 95% CrI 0.36 to 0.71; 80 participants; 2 studies; very low-quality evidence); blood loss (MD \u22120.34 L, 95% CrI \u22120.46 to \u22120.22; 237 participants; 4 studies; very low-quality evidence), total hospital stay (MD \u22122.42 days, 95% CrI \u22123.91 to \u22120.94; 197 participants; 3 studies; very low-quality evidence), and operating time (MD \u221215.32 minutes, 95% CrI \u221229.03 to \u22121.69; 192 participants; 4 studies; very low-quality evidence) were lower with low central venous pressure than with control. For the other comparisons, the evidence for difference was either based on single small trials or there was no evidence of differences. None of the trials reported health-related quality of life or time needed to return to work. Paucity of data meant that we could not assess transitivity assumptions and inconsistency for most analyses. When direct and indirect comparisons were available, network meta-analysis provided additional effect estimates for comparisons where there were no direct comparisons. However, the paucity of data decreases the confidence in the results of the network meta-analysis. Low-quality evidence suggests that liver resection using a radiofrequency dissecting sealer may be associated with more adverse events than with the clamp-crush method. Low-quality evidence also suggests that the proportion of people requiring a blood transfusion is higher with low central venous pressure than with acute normovolemic haemodilution plus low central venous pressure; very low-quality evidence suggests that blood transfusion quantity (red blood cells) was lower with fibrin sealant than control; blood transfusion quantity (fresh frozen plasma) was higher with oxidised cellulose than with fibrin sealant; and blood loss, total hospital stay, and operating time were lower with low central venous pressure than with control. There is no evidence to suggest that using special equipment for liver resection is of any benefit in decreasing the mortality, morbidity, or blood transfusion requirements (very low-quality evidence). Radiofrequency dissecting sealer should not be used outside the clinical trial setting since there is low-quality evidence for increased harm without any evidence of benefits. In addition, it should be noted that the sample size was small and the credible intervals were wide, and we cannot rule out considerable benefit or harm with a specific method of liver resection.",
        "gold": "We identified 67 randomised clinical trials involving a total of 6197 participants that met our inclusion criteria. However, we were only able to include 5771 participants from 64 trials since investigators either did not include the remaining participants in the analysis or did not report any outcomes of interest. Source of funding: 24 trials (35.8%) were funded by parties with no financial interest in obtaining positive results for the treatment being evaluated. The remaining trials received funding from either parties who would gain financially from the results of the study or did not report the funding. All the trials were at high risk of bias, that is, investigators may have overestimated the benefits or underestimated the harms of one method or the other because of the way that the studies were conducted. Many trials included few participants, and there was a good chance of arriving at the wrong conclusions because of this. The overall quality of evidence was low or very low. There was no evidence of differences in most of the comparisons, and where there was, these differences were in single trials, mostly of small sample size. Such evidence is unreliable. So, we mention only the evidence that was available in more than one trial. Of the primary outcomes, the only one where there was evidence of difference was in the number of adverse events, which was higher with radiofrequency dissecting sealer than with clamp-crush method. Among the secondary outcomes, the only evidence of difference was in the following: Blood transfusion (percentage): higher in the low central venous pressure group than in the acute normovolemic haemodilution (diluting the blood by giving fluids during operation) plus low central venous pressure group. Blood transfusion amount: lower in the fibrin sealant group (a type of glue applied to the cut surface of the liver) than in the control. Blood transfusion (fresh frozen plasma \u2212 a component of blood): higher in the oxidised cellulose (another type of glue applied to the cut surface of the liver) group than in the fibrin sealant group. Blood loss, total hospital stay, and operating time: lower with the low central venous pressure group than control. For other comparisons, the evidence for difference was based on single small trials, or there was no evidence of differences. None of the trials reported health-related quality of life or time needed to return to work. There is no evidence to suggest that using special equipment for liver resection is of any benefit."
    },
    {
        "index": "cochrane-simplification-test-26",
        "sentence": "Twenty-three trials involving 724 people were included. There is evidence supporting the use of systemic retinoids (improvement rate difference 44%, 95 CI 28 to 59%), oral PUVA (improvement rate difference 44%, 95 CI 26 to 62%). However, a combination of PUVA and retinoids is better than the individual treatments. The use of topical steroid under hydrocolloid occlusion is beneficial. It would also appear that low dose ciclosporin, tetracycline antibiotics and Grenz Ray Therapy may be useful in treating PPP. Colchicine has a lot of side effects and it is unclear if it is effective and neither was topical PUVA (rate difference of 0.00, 95% CI -0.04 to +0.04). There is no evidence to suggest that short-term treatment with hydroxycarbamide (hydroxyurea) is effective. Many different interventions were reported to produce \"improvement\" in PPP. There is, however, no standardised method for assessing response to treatment, and reductions in pustule counts or other empirical semi-quantitative scoring systems may be of little relevance to the patient. This review has shown that the ideal treatment for PPP remains elusive and that the standards of study design and reporting need to be improved to inform patients and those treating them of the relative merits of the many treatments available to them.",
        "gold": "The review of trials found that several treatments improve the symptoms of chronic palmoplantar pustulosis, although no treatment was shown to suppress the condition completely. Oral retinoid therapy (acitretin) appears to be helpful at relieving symptoms, particularly if combined with PUVA. Ciclosporin and tetracycline antibiotics can also provide some relief. Topical treatments were generally less helpful. As yet there is no ideal treatment for chronic palmoplantar pustulosis, though oral retinoids, particularly when combined with psoralens and ultraviolet radiation (PUVA), may help"
    },
    {
        "index": "cochrane-simplification-test-27",
        "sentence": "Nine trials evaluated the dose-related blood pressure-lowering efficacy of five drugs within the loop diuretics class (furosemide 40 mg to 60 mg, cicletanine 100 mg to 150 mg, piretanide 3 mg to 6 mg, indacrinone enantiomer -2.5 mg to -10.0/+80 mg, and etozolin 200 mg) in 460 people with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of systolic/diastolic blood pressure-lowering efficacy of loop diuretics was -7.9 (-10.4 to -5.4) mmHg/ -4.4 (-5.9 to -2.8) mmHg. Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference. We performed additional searches in 2012 and 2014, which found no additional trials meeting the minimum inclusion criteria. Based on the limited number of published RCTs, the systolic/diastolic blood pressure-lowering effect of loop diuretics is -8/-4 mmHg, which is likely an overestimate. We graded the quality of evidence for both systolic and diastolic blood pressure estimates as \"low\" due to the high risk of bias of included studies and the high likelihood of publication bias. We found no clinically meaningful blood pressure-lowering differences between different drugs within the loop diuretic class. The dose-ranging effects of loop diuretics could not be evaluated. The review did not provide a good estimate of the incidence of harms associated with loop diuretics because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.",
        "gold": "We searched the available scientific literature to find all the trials that had addressed these questions. We found 9 trials studying the blood pressure-lowering ability of 5 different loop diuretics (furosemide, cicletanine, piretanide, indacrinone and etozolin) in 460 participants. The blood pressure-lowering effect was modest, with systolic pressure lowered by 8 mmHg and diastolic pressure by 4 mmHg. No loop diuretic drug appears to be any better or worse than others in terms of blood pressure-lowering ability. Due to lack of reporting and the short duration of included trials, this review could not provide an estimate of the harms associated with loop diuretics."
    },
    {
        "index": "cochrane-simplification-test-28",
        "sentence": "We included 58 trials, of which 48 trials with 2849 participants randomised to intraperitoneal local anaesthetic instillation (1558 participants) versus control (1291 participants) contributed data to one or more of the outcomes. All the trials except one trial with 30 participants were at high risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Various intraperitoneal local anaesthetic agents were used but bupivacaine in the liquid form was the most common local anaesthetic used. There were considerable differences in the methods of local anaesthetic instillation including the location (subdiaphragmatic, gallbladder bed, or both locations) and timing (before or after the removal of gallbladder) between the trials. There was no mortality in either group in the eight trials that reported mortality (0/236 (0%) in local anaesthetic instillation versus 0/210 (0%) in control group; very low quality evidence). One participant experienced the outcome of serious morbidity (eight trials; 446 participants; 1/236 (0.4%) in local anaesthetic instillation group versus 0/210 (0%) in the control group; RR 3.00; 95% CI 0.13 to 67.06; very low quality evidence). Although the remaining trials did not report the overall morbidity, three trials (190 participants) reported that there were no intra-operative complications. Twenty trials reported that there were no serious adverse events in any of the 715 participants who received local anaesthetic instillation. None of the trials reported participant quality of life, return to normal activity, or return to work. The effect of local anaesthetic instillation on the proportion of participants discharged as day surgery between the two groups was imprecise and compatible with benefit and no difference of intervention (three trials; 242 participants; 89/160 (adjusted proportion 61.0%) in local anaesthetic instillation group versus 40/82 (48.8%) in control group; RR 1.25; 95% CI 0.99 to 1.58; very low quality evidence). The MD in length of hospital stay was 0.04 days (95% CI -0.23 to 0.32; five trials; 335 participants; low quality evidence). The pain scores as measured by the visual analogue scale (VAS) were significantly lower in the local anaesthetic instillation group than the control group at four to eight hours (32 trials; 2020 participants; MD -0.99 cm; 95% CI -1.10 to -0.88 on a VAS scale of 0 to 10 cm; very low quality evidence) and at nine to 24 hours (29 trials; 1787 participants; MD -0.53 cm; 95% CI -0.62 to -0.44; very low quality evidence). Various subgroup analyses and meta-regressions to investigate the influence of the different local anaesthetic agents, different methods of local anaesthetic instillation, and different controls on the effectiveness of local anaesthetic intraperitoneal instillation were inconsistent. Serious adverse events were rare in studies evaluating local anaesthetic intraperitoneal instillation (very low quality evidence). There is very low quality evidence that it reduces pain in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the clinical importance of this reduction in pain is unknown and likely to be small. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.",
        "gold": "We identified 58 trials, of which 48 randomised clinical trials involving 2849 people undergoing laparoscopic cholecystectomy contributed data to one or more of the outcomes. Most participants in the trials were low anaesthetic risk people undergoing planned laparoscopic cholecystectomy. The choice of whether the participants received local anaesthetic agents (or not) was determined by a method similar to the toss of a coin so that the treatments compared were conducted in people who were as similar as possible. There were no deaths in either group in eight trials (446 participants) that reported deaths. The studies reported very few or no serious complications in the groups. There were no local anaesthetic-related complications in nearly 1000 participants who received intra-abdominal local anaesthetic administration in the different trials that reported complications. None of the trials reported quality of life, the time taken to return to normal activity, or the time taken to return to work. The small differences in hospital stay between the two groups were imprecise. Pain scores were lower in the participants who received intra-abdominal local anaesthetic administration compared with those who received controls at four to eight hours and at nine to 24 hours as measured by the visual analogue scale (a chart that rates the amount of pain on a scale of 1 to 10). Most of the trials were of high risk of bias, that means that there is possibility of arriving at wrong conclusions overestimating benefits or underestimating harms of one method or the other because of the way that the study was conducted. Overall, the quality of evidence was very low. Serious adverse event rates were low in studies evaluating local anaesthetic intra-abdominal administration (very low quality evidence). There is very low quality evidence that local anaesthetic intra-abdominal administration reduces pain in low anaesthetic risk people undergoing planned laparoscopic cholecystectomy. However, the clinical importance of this reduction in pain is likely to be small. Further trials are necessary. Such trials should include outcomes such as quality of life, the time taken to return to normal activity, and the time taken to return to work, which are important for the person undergoing laparoscopic cholecystectomy and the people who provide funds for the treatment."
    },
    {
        "index": "cochrane-simplification-test-29",
        "sentence": "We identified 74 unique studies as eligible for this review and categorized them according to the antigens they detected. Types 1 to 3 include HRP-2 (fromP. falciparum) either by itself or with other antigens. Types 4 and 5 included pLDH (from P. falciparum) either by itself or with other antigens. In comparisons with microscopy, we identified 71 evaluations of Type 1 tests, eight evaluations of Type 2 tests and five evaluations of Type 3 tests. In meta-analyses, average sensitivities and specificities (95% CI) were 94.8% (93.1% to 96.1%) and 95.2% (93.2% to 96.7%) for Type 1 tests, 96.0% (94.0% to 97.3%) and 95.3% (87.3% to 98.3%) for Type 2 tests, and 99.5% (71.0% to 100.0%) and 90.6% (80.5% to 95.7%) for Type 3 tests, respectively. Overall for HRP-2, the meta-analytical average sensitivity and specificity (95% CI) were 95.0% (93.5% to 96.2%) and 95.2% (93.4% to 99.4%), respectively. For pLDH antibody-based RDTs verified with microscopy, we identified 17 evaluations of Type 4 RDTs and three evaluations of Type 5 RDTs. In meta-analyses, average sensitivity for Type 4 tests was 91.5% (84.7% to 95.3%) and average specificity was 98.7% (96.9% to 99.5%).\u00a0For Type 5 tests, average sensitivity was 98.4% (95.1% to 99.5%) and average specificity was 97.5% (93.5% to 99.1%). Overall for pLDH, the meta-analytical average sensitivity and specificity (95% CI) were 93.2% (88.0% to 96.2%) and 98.5% (96.7% to 99.4%), respectively. For both categories of test, there was substantial heterogeneity in study results. Quality of the microscopy reference standard could only be assessed in 40% of studies due to inadequate reporting, but results did not seem to be influenced by the reporting quality. Overall, HRP-2 antibody-based tests (such as the Type 1 tests) tended to be more sensitive and were significantly less specific than pLDH-based tests (such as the Type 4 tests). If the point estimates for Type 1 and Type 4 tests are applied to a hypothetical cohort of 1000 patients where 30% of those presenting with symptoms have P. falciparum, Type 1 tests will miss 16 cases, and Type 4 tests will miss 26 cases. The number of people wrongly diagnosed with P. falciparum would be 34 with Type 1 tests, and nine with Type 4 tests. The sensitivity and specificity of all RDTs is\u00a0such that they can replace or extend the access of diagnostic services for uncomplicated P. falciparum malaria. HRP-2\u00a0antibody types may be more sensitive but are less specific than pLDH antibody-based tests, but the differences are small. The HRP-2 antigen persists even after effective treatment and so is not useful for detecting treatment failures.",
        "gold": "Standard diagnosis of malaria in the past has depended on blood microscopy, but this requires a technician and a laboratory, and is often not feasible for basic health services in many areas. Sometimes in research studies, another technique called polymerase chain reaction (PCR) is used, but again this requires equipment and trained staff, and cannot be used routinely. Technological advances have led to rapid diagnostic tests (RDTs) for malaria. These detect parasite-specific antigens in the blood, are simple to use, and can give results as a simple positive or negative result, within 15 minutes. This review evaluates the accuracy of RDTs compared with microscopy and PCR for detecting Plasmodium falciparum parasites in the blood. It includes 74 studies, giving a total of 111 RDT evaluations (of which 104 compared RDTs with microscopy), reporting a total of 60,396 RDT results. Results are presented by type of test, classified by the malaria antigen that they are designed to detect (either histidine-rich protein-2 (HRP-2), or plasmodium lactate dehydrogenase (pLDH)). The results indicate that RDTs can be very accurate compared to microscopy and PCR. The performance of RDT types varied but the differences were not large. HRP-2-based tests tended to be more sensitive (ie they identified more true cases of malaria) and less specific (ie they wrongly identified more malaria that was not present) than pLDH-based tests. Choice will depend on prevalence of malaria, and we provide data in this review to assist these decisions, although policy makers will also take into account other factors relating to cost and test stability."
    },
    {
        "index": "cochrane-simplification-test-30",
        "sentence": "Five studies met the inclusion criteria. All were conducted in the UK, and tested short-term changes in the consultation time allocated to each patient. Overall, our confidence in the results was very low; most studies had a high risk of bias, particularly due to non-random allocation of participants and the absence of data on participants' characteristics and small sample sizes. We are uncertain whether altering appointment length increases primary care consultation length, number of referrals and investigations, prescriptions, or patient satisfaction based on very low-certainty evidence. None of the studies reported on the effects of altering the length of consultation on resources used. We did not find sufficient evidence to support or refute a policy of altering the lengths of primary care physicians' consultations. It is possible that these findings may change if high-quality trials are reported in the future. Further trials are needed that focus on health outcomes and cost-effectiveness.",
        "gold": "We identified five studies conducted in the UK that tested whether methods to change consultation length for family doctors provides any benefit. The studies were conducted in single or multiple practices, and the number of appointments ranged from 200 to 2957 consultations. Four studies compared a change in appointment times from 5 to 15 minutes, and one study compared short versus long consultations with or without treatment for patients with no diagnosis. All studies tested short-term changes in the consultation time allocated to each patient. Our confidence in the results of these studies is very low. Consequently, we are not certain whether changing appointment slots leads to an actual increase of the length of the consultation, number of referrals and investigations requested by the doctor, and number of medications prescribed. Likewise, it is unclear whether patients are more satisfied with the health care they receive when appointments are longer. None of the studies reported on the resources associated with lengthening appointments. There is currently not enough evidence to say whether altering the amount of time that doctors consult with patients provides benefits or not."
    },
    {
        "index": "cochrane-simplification-test-31",
        "sentence": "The search identified 3952 abstracts which were scanned for relevance. Three trials met the inclusion criteria (Milinkovic 2007; McComsey 2008; Sanchez-Conde 2005). All three trials were conducted in developed countries, participants were ART experienced and all had sustained virologic suppression at baseline. A total of 157 participants were recruited to the trials. Sample sizes ranged from 24 to 92 and more than 79% of participants were male.The studies were at a high risk of selection, performance/detection and selective outcome reporting biases. Some baseline characteristics differed among the groups, including triglyceride levels in two studies and body mass index in one study. In light of variation in the design and follow-up of the study results, no meta-analysis was performed and the results of single studies are presented. There was no significant difference in virologic suppression in the included studies (Milinkovic 2007; McComsey 2008; Sanchez-Conde 2005); Risk Ratio (RR) 1.09 (95% CI: 0.93 to 1.28), 0.94 (95% CI:0.59 to 1.50) and 1.03 (95% CI: 0.90 to 1.18) respectively. Symptomatic hyperlactatemia was seen in the high dose arm of the Milinkovic 2007 study; RR 0.21 (95% CI: 0.01 to 4.66), in no participants in the McComsey 2008 trial and not reported on in the Sanchez-Conde 2005 trial. McComsey 2008 and Milinkovic 2007 demonstrated a reduction in bone mineral density (BMD), reduction in limb fat and an increase in triglycerides in the high dose arms. The studies did not indicate that any participants discontinued treatment due to adverse events. This systematic review identified only three small trials that evaluated virologic efficacy and safety of high dose versus low dose stavudine. All three trials were conducted in developed countries and none reported from developing countries yet stavudine remains a component of ART combination therapy in many developing countries. It was not possible to perform a meta-analysis on these trails. Individual results from the trials were imprecise and have not identified a clear advantage in virologic efficacy or safety between low and high dose stavudine. Furthermore, enrolled participants were treatment experienced with sustained virologic suppression and so existing data cannot be generalized to settings where stavudine is currently used in ART naive patients with high viral loads. Stavudine dose reduction trials in ART naive patients, in developing countries where stavudine is still being used are warranted as the phasing out of stavudine that is recommended by WHO may not be immediately universally feasible.",
        "gold": "The comprehensive search strategy developed by the Cochrane HIV/AIDS Review Group was used to identify trials that compared the safety and efficacy in suppressing the viral load of low dose versus high dose stavudine in the context of treating HIV-1 with combination antiretroviral therapy. The searches covered the period 1996 to 2014.The search identified 3952 trials and only three met the inclusion criteria, all the included trials were conducted in developed countries, the number of participants ranged from 24 to 92 and the majority were male. The efficacy of suppressing the viral load was found to be the same in all the trials whether high dose or low dose of stavudine was used. McComsey 2008 and Milinkovic 2007 demonstrated a reduction in bone mineral density (BMD), reduction in limb fat and an increase in triglycerides in the high dose arms. While there was no demonstration of a difference in efficacy of viral load suppression between high dose and low dose stavudine in the included trials, participants included in these trials were already treated with antiretroviral therapy and had suppressed viral load. The fact that participants already had suppression of the viral load and the studies were small, meant it would be difficult to demonstrate the differences in viral load suppression between the two groups. The studies did not indicate that any participants discontinued treatment due to adverse events. This review identified only trials that tested the safety and efficacy in suppressing the viral load of low dose compared to high dose stavudine. These trials were small, conducted in developed countries and included participants with suppressed viral loads that had been on antiretroviral treatment for a long time. Individual results from the trials have not identified a clear advantage in viral load suppression or safety between low and high dose stavudine.Studies that evaluate the safety and efficacy in viral load suppression need to be conducted particularly in developing countries where stavudine is still being used and probably needed to either sustain treatment programs or where alternatives are limited."
    },
    {
        "index": "cochrane-simplification-test-32",
        "sentence": "Ten trials met the inclusion criteria for this review (n = 1658 participants). We found five trials to be at low risk of bias and five to be at moderate risk of bias. Six of the trials included recruitment manoeuvres as part of an open lung ventilation strategy that was different from control ventilation in aspects other than the recruitment manoeuvre (such as mode of ventilation, higher positive end-expiratory pressure (PEEP) titration and lower tidal volume or plateau pressure). Six studies reported mortality outcomes. Pooled data from five trials (1370 participants) showed a reduction in intensive care unit (ICU) mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.72 to 0.97, P = 0.02, low-quality evidence), pooled data from five trials (1450 participants) showed no difference in 28-day mortality (RR 0.86, 95% CI 0.74 to 1.01, P = 0.06, low-quality evidence) and pooled data from four trials (1313 participants) showed no difference in in-hospital mortality (RR 0.88, 95% CI 0.77 to 1.01, P = 0.07, low-quality evidence). Data revealed no differences in risk of barotrauma (RR 1.09, 95% CI 0.78 to 1.53, P = 0.60, seven studies, 1508 participants, moderate-quality evidence). We identified significant clinical heterogeneity in the 10 included trials. Results are based upon the findings of several (five) trials that included an \"open lung ventilation strategy\", whereby the intervention group differed from the control group in aspects other than the recruitment manoeuvre (including co-interventions such as higher PEEP, different modes of ventilation and higher plateau pressure), making interpretation of the results difficult. A ventilation strategy that included recruitment manoeuvres in participants with ARDS reduced intensive care unit mortality without increasing the risk of barotrauma but had no effect on 28-day and hospital mortality. We downgraded the quality of the evidence to low, as most of the included trials provided co-interventions as part of an open lung ventilation strategy, and this might have influenced results of the outcome.",
        "gold": "We included 10 trials in this review, which included a total of 1658 participants with acute respiratory distress syndrome. Low-quality evidence suggests that recruitment manoeuvres improve ICU survival but not 28-day or hospital survival. Recruitment manoeuvres have no effect on the risk of air leakage from the lungs. We found the evidence for most outcomes to be of low to moderate quality, primarily because of the design of included trials. Many trials used the recruitment manoeuvre in conjunction with other ventilation techniques or strategies, and this might have influenced outcomes. Caution should be applied when conclusions are drawn about the effectiveness of the recruitment manoeuvre alone."
    },
    {
        "index": "cochrane-simplification-test-33",
        "sentence": "Fifteen studies, involving 687 participants, were included in the review. Study quality was poor and sample sizes were frequently small. However, some pooled effects were analysed. Three studies measured our primary outcome but individually did not report significant differences between treatment and control. The use of 'as needed' medications was reduced in two studies, (47 patients), by relaxation therapy (OR 4.47, CI 1.22 to 16.44). There was no significant difference in FEV1 for relaxation therapy in four studies of 150 patients, (SMD -0.01, CI -0.41 to 0.40). Quality of life, measured using the Asthma Quality of Life Questionnaire in two studies, (48 patients), showed a positive effect following CBT (WMD 0.71, CI 0.23 to 1.19). Peak Expiratory Flow outcome data in two studies, (51 patients), indicated a significant difference in favour of bio-feedback therapy (SMD 0.66, CI 0.09 to 1.23) but no significant difference following relaxation therapy (WMD 43 L/min, CI -5 to 92 L/min). There was no statistically significant improvement in depression levels following relaxation therapy (SMD 0.17, CI -0.25 to 0.59). The remainder of the findings between studies were conflicting. This may have been due to the different types of interventions used and the deficiencies in trial design. This review was unable to draw firm conclusions for the role of psychological interventions in asthma due to the absence of an adequate evidence base. Larger, well-conducted and reported randomised trials are required in this area, in order to determine the effects of these techniques in the treatment of asthma in adults.",
        "gold": "Systematically, we searched the literature on psychological interventions to find valid studies that looked at the effects of providing mainly psychological interventions for adults with asthma. The studies found examined many different therapies and measured different physical and psychological outcomes; for these reasons, their results could not be easily combined. However, meta-analyses could be performed to determine the effect of Cognitive Behavioural Therapy (CBT) on quality of life, bio-feedback on PEF, and relaxation therapy on PEF and FEV1 and medication use. The available studies were completed with small numbers of people and the way the studies were conducted could be improved. More research with larger numbers of people and improved design needs to be done before it is known whether psychological interventions are effective in improving health outcomes for adults with asthma."
    },
    {
        "index": "cochrane-simplification-test-34",
        "sentence": "Thirty-five studies, including 6785 participants overall (of which 5365 in the arms of interest (antidepressant and benzodiazepines as monotherapy)) were included in this review; however, since studies addressed many different comparisons, only a few trials provided data for primary outcomes. We found low-quality evidence suggesting no difference between antidepressants and benzodiazepines in terms of response rate (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.67 to 1.47; participants = 215; studies = 2). Very low-quality evidence suggested a benefit for benzodiazepines compared to antidepressants in terms of dropouts due to any cause, even if confidence interval (CI) ranges from almost no difference to benefit with benzodiazepines (RR 1.64, 95% CI 1.03 to 2.63; participants = 1449; studies = 7). We found some evidence suggesting that serotonin reuptake inhibitors (SSRIs) are better tolerated than TCAs (when looking at the number of patients experiencing adverse effects). We failed to find clinically significant differences between individual benzodiazepines. The majority of studies did not report details on random sequence generation and allocation concealment; similarly, no details were provided about strategies to ensure blinding. The study protocol was not available for almost all studies so it is difficult to make a judgment on the possibility of outcome reporting bias. Information on adverse effects was very limited. The identified studies are not sufficient to comprehensively address the objectives of the present review. The majority of studies enrolled a small number of participants and did not provide data for all the outcomes specified in the protocol. For these reasons most of the analyses were underpowered and this limits the overall completeness of evidence. In general, based on the results of the current review, the possible role of antidepressants and benzodiazepines should be assessed by the clinician on an individual basis. The choice of which antidepressant and/or benzodiazepine is prescribed can not be made on the basis of this review only, and should be based on evidence of antidepressants and benzodiazepines efficacy and tolerability, including data from placebo-controlled studies, as a whole. Data on long-term tolerability issues associated with antidepressants and benzodiazepines exposure should also be carefully considered. The present review highlights the need for further higher-quality studies comparing antidepressants with benzodiazepines, which should be conducted with high-methodological standards and including pragmatic outcome measures to provide clinicians with useful and practical data. Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.",
        "gold": "We did not find substantial differences between antidepressants and benzodiazepines in terms of efficacy and tolerability. There was not enough information to compare any differences in adverse effects. However, our findings are limited in the following ways: few studies contributed to each analysis, some studies were funded by pharmaceutical companies, and only short-term outcomes were assessed. The quality of the available evidence was mainly low, meaning that further research would be very likely to have an important impact on these results. Studies with larger sample sizes and fewer risks of bias should be carried out, with head-to-head comparisons. Longer-term outcomes need to be addressed to establish whether the effect is transient or durable. Trials should better report any harms experienced by participants during the trial. In addition, a network meta-analysis of psychopharmacological treatment in panic disorder will likely shed further light on this compelling issue, also being able to provide more information with regard to comparative efficacy."
    },
    {
        "index": "cochrane-simplification-test-35",
        "sentence": "Twenty-nine trials, that enrolled over 1,700 participants with pancreatic carcinoma, were included. Three eligible studies compared plastic stents to surgery. Endoscopic stenting with plastic stents was associated with a reduced risk of complications (RR 0.60, 95% CI 0.45 - 0.81), but with higher risk of recurrent biliary obstruction prior to death (RR 18.59, 95% CI 5.33 - 64.86) when compared with surgery. There was a trend towards lower risk of 30-day mortality with plastic stents (p=0.07, RR 0.58, 95% CI 0.32, 1.04). One published study compared metal stents to surgery and reported lower costs and better quality-of-life with metal stents.   Nine studies compared metal to plastic stents. Metal stents were associated with a lower risk of recurrent biliary obstruction than plastic stents (RR 0.48, 95% CI 0.38 - 0.62). There was no significant difference in risk of technical failure, therapeutic failure, complications or 30-day mortality by meta-analysis.   When different types of plastic stents were compared to polyethylene stents, only perflouro alkoxy plastic stents had superior outcomes in one trial. The addition of an anti-reflux valve improved the patency of Teflon stents. Endoscopic metal stents are the intervention of choice at present in patients with malignant distal obstructive jaundice due to pancreatic carcinoma. In patients with short predicted survival, their patency benefits over plastic stents may not be realised. Further RCTs are needed to determine the optimal stent type for these patients.",
        "gold": "This review compares 29 randomised controlled trials that used surgical by-pass, endoscopic metal stents or endoscopic plastic stents in patients with malignant bile duct obstruction. All included studies contained groups where cancer of the pancreas was the most common cause of bile duct obstruction. This review shows that endoscopic stents are preferable to surgery in palliation of malignant distal bile duct obstruction due to pancreatic cancer. The choice of metal or plastic stents depends on the expected survival of the patient; metal stents only differ from plastic stents in the risk of recurrent bile duct obstruction. Polyethylene stents and stainless-steel alloy stents (Wallstent) are the most studied stents."
    },
    {
        "index": "cochrane-simplification-test-36",
        "sentence": "We included five RCTs reporting 444 arterial cannulations in paediatric participants. Four RCTs compared ultrasound with palpation, and one compared ultrasound with Doppler auditory assistance. Risk of bias varied across studies, with some studies lacking details of allocation concealment. It was not possible to blind practitioners in all of the included studies; this adds a performance bias that is inherent to the type of intervention studied in our review. Only two studies reported the rate of complications. Meta-analysis showed that ultrasound guidance produces superior success rates at first attempt (risk ratio (RR) 1.96, 95% confidence interval (CI) 1.34 to 2.85, 404 catheters, four RCTs, moderate-quality evidence) and fewer complications, such as haematoma formation (RR 0.20, 95% CI 0.07 to 0.60, 222 catheters, two RCTs, moderate-quality evidence). Our results suggest, but do not confirm, that a possible advantage of ultrasound guidance for the first attempt success rate over other techniques is more pronounced in infants and small children than in older children. Similarly, our results suggest, but do not confirm, the possibility of a positive influence of expertise in the use of ultrasound on the first attempt success rate. We also found improved success rates within two attempts (RR 1.78, 95% CI 1.25 to 2.51, 134 catheters, two RCTs, moderate-quality evidence) with ultrasound guidance compared with other types of guidance. No studies reported data about ischaemic damage. We rated the quality of evidence for all outcomes as moderate owing to imprecision due to wide confidence intervals, modest sample sizes and limited numbers of events. We identified moderate-quality evidence suggesting that ultrasound guidance for radial artery cannulation improves first and second attempt success rates and decreases the rate of complications as compared with palpation or Doppler auditory assistance. The improved success rate at the first attempt may be more pronounced in infants and small children, in whom arterial line cannulation is more challenging than in older children.",
        "gold": "The evidence is current to January 2016. We found five eligible studies - four comparing ultrasound with palpation and one comparing ultrasound with Doppler auditory assistance. We included in the review children aged one month to 18 years. We found that ultrasound increased the rate of successful cannulation at the first attempt and reduced the formation of haematomas. Ultrasound also increased the success rate within two attempts. It is likely that ultrasound is more useful for infants and small children than for older children. It is also likely that ultrasound is more useful if the practitioner is experienced in its use. We noted variation in the risk of bias of included studies. We rated the quality of evidence as moderate mainly because the number of studies was limited. For the same reason, we could not confirm the effect of age and expertise in ultrasound usage. Our evidence suggests that ultrasound is superior to other techniques for arterial catheter insertion, particularly in babies and young children."
    },
    {
        "index": "cochrane-simplification-test-37",
        "sentence": "We included one small RCT (80 male student participants conducted in the Netherlands and published in 2009) and three ITS studies (general population studies in Canadian provinces conducted in the 1970s and 80s). The RCT found that young men exposed to movies with a low-alcohol content drank less than men exposed to movies with a high-alcohol content (mean difference (MD) -0.65 drinks; 95% CI -1.2, -0.07; p value = 0.03, very-low-quality evidence). Young men exposed to commercials with a neutral content compared with those exposed to commercials for alcohol drank less (MD -0.73 drinks; 95% CI -1.30, -0.16; p value = 0.01, very-low-quality evidence). Outcomes were assessed immediately after the end of the intervention (lasting 1.5 hours), so no follow-up data were available. Using the Grading of Recommendations Assessment, Development and Evaluation approach, the quality of the evidence was rated as very low due to a serious risk of bias, serious indirectness of the included population and serious level of imprecision. Two of the ITS studies evaluated the implementation of an advertising ban and one study evaluated the lifting of such a ban. Each of the three ITS studies evaluated a different type of ban (partial or full) compared with different degrees of restrictions or no restrictions during the control period. The results from the three ITS studies were inconsistent. A meta-analysis of the two studies that evaluated the implementation of a ban showed an overall mean non-significant increase in beer consumption in the general population of 1.10% following the ban (95% CI -5.26, 7.47; p value = 0.43; I2 = 83%, very-low-quality evidence). This finding is consistent with an increase, no difference, or a decrease in alcohol consumption. In the study evaluating the lifting of a total ban on all forms of alcohol advertising to a partial ban on spirits advertising only, which utilised an Abrupt Auto-regressive Integrated Moving Average model, the volume of all forms of alcohol sales decreased by 11.11 kilolitres (95% CI -27.56, 5.34; p value = 0.19) per month after the ban was lifted. In this model, beer and wine sales increased per month by 14.89 kilolitres (95% CI 0.39, 29.39; p value = 0.04) and 1.15 kilolitres (95% CI -0.91, 3.21; p value = 0.27), respectively, and spirits sales decreased statistically significantly by 22.49 kilolitres (95% CI -36.83, -8.15; p value = 0.002). Using the GRADE approach, the evidence from the ITS studies was rated as very low due to a high risk of bias arising from a lack of randomisation and imprecision in the results. No other prespecified outcomes (including economic loss or hardship due to decreased alcohol sales) were addressed in the included studies and no adverse effects were reported in any of the studies. None of the studies were funded by the alcohol or advertising industries. There is a lack of robust evidence for or against recommending the implementation of alcohol advertising restrictions. Advertising restrictions should be implemented within a high-quality, well-monitored research programme to ensure the evaluation over time of all relevant outcomes in order to build the evidence base.",
        "gold": "The evidence we present is current to May 2014. We found four studies that evaluated the restriction or banning of alcohol advertising via any format. One was a small randomised controlled trial (RCT) that evaluated drinking behaviour in 80 young men in the Netherlands exposed to movies with either a high or low alcohol content combined with a commercial with either a neutral content (interpreted as a ban on alcohol advertising) or a high alcohol content. The other three studies were interrupted time series (ITS) studies. ITS studies are studies in which changes, usually in the general public, are measured at various points before, during and after an intervention such as a change in policy. Two of the three ITS studies evaluated what happened after an advertising ban was introduced by two different Canadian provincial governments. The third ITS study evaluated what happened after a ban was lifted after being in place for 50 years in another Canadian province. Each study evaluated a different category of ban (either partial or full). None of the above studies were funded by the alcohol or advertising industries. The data arising from the included studies did not show a clear effect either for or against the banning or restriction of alcohol advertising. In the RCT, young men who watched movies with a low-alcohol content drank less than men who watched movies with a high-alcohol content. Young men exposed to commercials with a neutral content compared with those exposed to commercials for alcohol drank less. The trial was one and a half hours, so we do not know how long beyond the trial these effects lasted. The trial did not report on any harmful outcomes. The results from the three ITS studies were inconsistent. We statistically combined the results of the two studies that assessed what happened after a ban was introduced. This showed an overall increase in beer consumption in the general population following the introduction of the ban, but the results were uncertain and could also be consistent with no difference or an overall decrease in alcohol consumption. The third ITS study, which evaluated the lifting of a total ban on all forms of alcohol advertising to a ban on spirits advertising only, also found uncertain results. None of the studies reported on any harms arising from the bans. Overall we judged the quality of evidence to be very low in the RCT. This was based on the fact that there were problems with the study methodology, the population included men only and the results were not very accurate. In the ITS studies, the quality was also judged to be very low due to problems with the study methodology and the results not being precise. The review cannot recommend for or against banning alcohol advertising. Governments that are considering implementing alcohol advertising bans would be advised to implement the ban in a research environment and monitor the effects over time to build the evidence base."
    },
    {
        "index": "cochrane-simplification-test-38",
        "sentence": "Eight randomized trials studying a total of 182 infants were included. There was no evidence of difference in short-term growth parameters when high and low MCT formulas were compared. The meta-analysis of weight gain based on five studies yielded a WMD of -0.35 g/kg/d (95% CI -1.44, 0.74). Similarly, meta-analysis of weight gain in g/d based on two studies showed no evidence of difference (WMD 2.09 g/d, 95% CI -1.46, 5.64). Length gain, based on five studies, showed a non-significant WMD of 0.14 cm/wk (95% CI -0.04, 0.31). Head circumference gain, based on data from five studies, showed a non-significant WMD -0.03 cm/wk (95% CI -0.15, 0.08). Only one study reported a statistically non-significant skin fold thickness gain, with a mean difference -0.15 mm/wk (95% CI -0.41, 0.11). Subgroup analyses according to % MCT in the high MCT formula, by 10% intervals showed no evidence of effect of high MCT on short-term weight gain within any subgroup. There are conflicting data (two studies) as to formula tolerance. There is no evidence of effect on incidence of necrotizing enterocolitis (NEC), based on small numbers in two trials. No studies were located addressing long-term growth parameters or neurodevelopmental outcomes. There is no evidence of difference between MCT and LCT on short-term growth, gastrointestinal intolerance, or necrotizing enterocolitis. Therefore, neither formula type could be concluded to improve short-term growth or have less adverse effects. Further studies are necessary because the results from the included eight studies are imprecise due to small numbers and do not address important long-term outcomes. Additional research should aim to clarify effects on formula tolerance and on long-term growth and neurodevelopmental outcomes, and include larger study populations to better evaluate effect on NEC incidence.",
        "gold": "The review authors searched the medical literature. They found eight small controlled randomized studies looking at short-term growth (weight, length, and head circumference gain) in preterm infants fed with varying amounts of medium chain fats. The pattern of growth in infants fed exclusively with high MCT or low MCT formula for at least one week did not differ (five studies with 182 infants). These infants had a mean gestational age between 29 and 32 weeks, mean birth weights between 1 kg and 1.5 kg, and were aged one to six weeks. One study found a high degree of gastrointestinal intolerance with high MCT content and another did not. Development of necrotizing enterocolitis was not different. No studies addressed long-term growth or neurodevelopmental outcomes."
    },
    {
        "index": "cochrane-simplification-test-39",
        "sentence": "We included one small trial (with data from 34 participants) comparing transcervical amnioinfusion with no amnioinfusion. The trial was considered to be at a high risk of bias overall, due to small numbers, inconsistency in the reporting and lack of information on blinding. Meta-analysis was not possible. Transcervical amnioinfusion was with room temperature saline at 10 mL per minute for 60 minutes, then 3 mL per minute until delivery versus no amnioinfusion. All women received intrauterine pressure catheter, acetaminophen and antibiotics (ampicillin or, if receiving Group B beta streptococcal prophylaxis, penicillin and gentamycin). We did not identify any trials that used transabdominal amnioinfusion. Compared to no amnioinfusion, transcervical amnioinfusion had no clear effect on the incidence of postpartum endometritis (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.29 to 7.87; absolute risk 176/1000 (95% CI 34 to 96) versus 118/1000;low-quality evidence). Nor was there a clear effect in the incidence of neonatal infection (RR 3.00, 95% CI 0.13 to 68.84; absolute risk 0/1000 (95% CI 0 to 0) versus 0/1000; low-quality evidence). The outcome of perinatal death or severe morbidity (such as neonatal encephalopathy, intraventricular haemorrhage, admission to intensive/high care) was not reported in the included trial. In terms of this review's secondary outcomes, the rate of caesarean section was the same in both groups (RR 1.00, 95% CI 0.35 to 2.83; absolute risk 294/1000 (95% CI 103 to 832) versus 294/1000; low-quality evidence). There was no clear difference in the duration of maternal antibiotic treatment between the amnioinfusion and no amnioinfusion control group (mean difference (MD) 16 hours, 95% CI -1.75 to 33.75); nor in the duration of hospitalisation (MD 3.00 hours, 95% CI -15.49 to 21.49). The study did not report any information about how many babies had a low Apgar score at five minutes after birth. Women in the amnioinfusion group had a lower temperature at delivery compared to women in the control group (MD -0.38\u00b0C, 95% CI -0.74 to -0.02) but this outcome was not pre-specified in the protocol for this review. The majority of this review's secondary outcomes were not reported in the included study. There is insufficient evidence to fully evaluate the effectiveness of using transcervical amnioinfusion for chorioamnionitis and to assess the safety of this intervention or women\u2019s satisfaction. We did not identify any trials that used transabdominal amnioinfusion. The evidence in this review can neither support nor refute the use of transcervical amnioinfusion outside of clinical trials. We included one small study that reported on a limited number of outcomes of interest in this review. The numbers included in this review are too small for meaningful assessment of substantive outcomes, where reported. For those outcomes we assessed using GRADE (postpartum endometritis, neonatal infection, and caesarean section), we downgraded the quality of the evidence to low - with downgrading decisions based on small numbers and a lack of information on blinding. The included study did not report on this review's other primary outcome (perinatal death or severe morbidity). The reduction in pyrexia, though not a pre-specified outcome of this review, may be of relevance in terms of benefits to the fetus of reduced exposure to heat. We postulate that the temperature reduction found may be a direct cooling effect of amnioinfusion with room temperature fluid, rather than reduction of infection. Larger trials are needed to confirm and extend the findings of the trial reviewed here. These should be randomised controlled trials; participants, women with chorioamnionitis; interventions, amnioinfusion; comparisons, no amnioinfusion; outcomes, maternal and perinatal outcomes including neurodevelopmental measures. Further research is justified to determine possible benefits or risks of amnioinfusion for chorioamnionitis, and to investigate possible benefits of reducing temperature in fetuses considered at risk of neurological damage. Research should include randomised trials to examine transcervical or transabdominal amnioinfusion compared with no infusion for chorioamnionitis and examine outcomes listed in the methods of this review.",
        "gold": "We searched for evidence on 6 July 2016 and only found one randomised controlled trial (which reported data from a total of 34 women). Data were available for 17 women who received transcervical amnioinfusion and 17 women who did not. All of the women received paracetamol and antibiotics and they also had a special type of catheter inserted into the cervix to measure information about their contractions (i.e. how often the contractions occur, how long they lasted and how strong they were). infection of the mother's womb after the birth(low-quality evidence);infection of the baby(low-quality evidence);caesarean section(low-quality evidence);duration of antibiotic treatment; norduration of hospital stay. Themother's temperature at delivery, which was not a pre-defined outcome for our review, was lower in the women who received amnioinfusion, by 0.38 \u00b0C (with a likely range of 0.74 lower to 0.02 lower). The outcomedeath or severe illness in the babywas not reported, nor did the study report on the number of babies with alow Apgar scoreafter they were born (a low Apgar score could indicate that the baby is in need of medical attention). Similarly, the majority of other outcomes listed in this review were not reported in the included study. We did not identify any studies that looked at introducing the solution through the mother's abdomen (transabdominal route). There is not enough evidence to support the use of amnioinfusion for chorioamnionitis in clinical practice. We suggest that the reduction in temperature may have been in part due to a direct cooling effect of the infused fluid, and that further research is justified to determine whether such a cooling effect may be beneficial for the baby. Further randomised controlled trials are needed in this area. Future trials should compare transabdominal or transcervical amnioinfusion with no amnioinfusion for women with pregnancy fluid and sac infection (chorioamnionitis) and report on important outcomes listed in this review."
    },
    {
        "index": "cochrane-simplification-test-40",
        "sentence": "Three studies met the inclusion criteria, with a total of 1620 participants. The sensitivities of the Mini-Cog in the individual studies were reported as 0.99, 0.76 and 0.99. The specificity of the Mini-Cog varied in the individual studies and was 0.93, 0.89 and 0.83. There was clinical and methodological heterogeneity between the studies which precluded a pooled meta-analysis of the results. Methodological limitations were present in all the studies introducing potential sources of bias, specifically with respect to the methods for participant selection. There are currently few studies assessing the diagnostic test accuracy of the Mini-Cog in community settings. The limited number of studies and the methodological limitations that are present in the current studies make it difficult to provide recommendations for or against the use of the Mini-Cog as a cognitive screening test in community settings. Additional well-designed studies comparing the Mini-Cog to other brief cognitive screening tests are required in order to determine the accuracy and utility of the Mini-Cog in community based settings.",
        "gold": "In this review, we searched medical literature databases to identify studies which evaluated how well the Mini-Cog is able to distinguish between individuals who have dementia and those who do not have dementia when compared to in-depth evaluation by dementia specialists. Our review focussed on those studies that were conducted in community based settings. We identified three unique randomised controlled studies that evaluated the Mini-Cog. In these studies the accuracy of the Mini-Cog varied and importantly there were some potential limitations within the studies which may have led to an overestimation of the accuracy of the Mini-Cog. Based on the information that we obtained from our review, we felt that further research into the accuracy of the Mini-Cog was required before it could be recommended for routine use for identifying dementia in community settings."
    },
    {
        "index": "cochrane-simplification-test-41",
        "sentence": "We included 19 studies that investigated three types of amphetamines: dexamphetamine (10.2 mg/d to 21.8 mg/d), lisdexamfetamine (30 mg/d to 70 mg/d), and mixed amphetamine salts (MAS; 12.5 mg/d to 80 mg/d). These studies enrolled 2521 participants; most were middle-aged (35.3 years), Caucasian males (57.2%), with a combined type of ADHD (78.8%). Eighteen studies were conducted in the USA, and one study was conducted in both Canada and the USA. Ten were multi-site studies. All studies were placebo-controlled, and three also included an active comparator: guanfacine, modafinil, or paroxetine. Most studies had short-term follow-up and a mean study length of 5.3 weeks. We found no studies that had low risk of bias in all domains of the Cochrane 'Risk of bias\u2019 tool, mainly because amphetamines have powerful subjective effects that may reveal the assigned treatment, but also because we noted attrition bias, and because we could not rule out the possibility of a carry-over effect in studies that used a cross-over design. Sixteen studies were funded by the pharmaceutical industry, one study was publicly funded, and two studies did not report their funding sources. Amphetamines versus placebo Severity of ADHD symptoms: we found low- to very low-quality evidence suggesting that amphetamines reduced the severity of ADHD symptoms as rated by clinicians (SMD \u22120.90, 95% confidence interval (CI) \u22121.04 to \u22120.75; 13 studies, 2028 participants) and patients (SMD \u22120.51, 95% CI \u22120.75 to \u22120.28; six studies, 120 participants). Retention: overall, we found low-quality evidence suggesting that amphetamines did not improve retention in treatment (risk ratio (RR) 1.06, 95% CI 0.99 to 1.13; 17 studies, 2323 participants). Adverse events: we found that amphetamines were associated with an increased proportion of patients who withdrew because of adverse events (RR 2.69, 95% CI 1.63 to 4.45; 17 studies, 2409 participants). Type of amphetamine: we found differences between amphetamines for the severity of ADHD symptoms as rated by clinicians. Both lisdexamfetamine (SMD \u22121.06, 95% CI \u22121.26 to \u22120.85; seven studies, 896 participants; low-quality evidence) and MAS (SMD \u22120.80, 95% CI \u22120.93 to \u22120.66; five studies, 1083 participants; low-quality evidence) reduced the severity of ADHD symptoms. In contrast, we found no evidence to suggest that dexamphetamine reduced the severity of ADHD symptoms (SMD \u22120.24, 95% CI \u22120.80 to 0.32; one study, 49 participants; very low-quality evidence). In addition, all amphetamines were efficacious in reducing the severity of ADHD symptoms as rated by patients (dexamphetamine: SMD \u22120.77, 95% CI \u22121.14 to \u22120.40; two studies, 35 participants; low-quality evidence; lisdexamfetamine: SMD \u22120.33, 95% CI \u22120.65 to \u22120.01; three studies, 67 participants; low-quality evidence; MAS: SMD \u22120.45, 95% CI \u22121.02 to 0.12; one study, 18 participants; very low-quality evidence). Dose at study completion: different doses of amphetamines did not appear to be associated with differences in efficacy. Type of drug-release formulation: we investigated immediate- and sustained-release formulations but found no differences between them for any outcome. Amphetamines versus other drugs We found no evidence that amphetamines improved ADHD symptom severity compared to other drug interventions. Amphetamines improved the severity of ADHD symptoms, as assessed by clinicians or patients, in the short term but did not improve retention to treatment. Amphetamines were associated with higher attrition due to adverse events. The short duration of studies coupled with their restrictive inclusion criteria limits the external validity of these findings. Furthermore, none of the included studies had an overall low risk of bias. Overall, the evidence generated by this review is of low or very low quality.",
        "gold": "Reviewers found 19 studies, which enrolled 2521 patients. Most patients were male (57.2%), middle-aged (mean age 35.3 years) Caucasians (84.5%). These studies compared amphetamines to placebo (something that looks like an amphetamine but with no active ingredient), and three studies also compared amphetamines with other drugs such as guanfacine, modafinil, and paroxetine. In this review, we assessed the effects of three different kinds of amphetamines: dexamphetamine (from 10.2 to 21.8 mg/d), lisdexamfetamine (from 30 to 70 mg/d), and mixed amphetamine salts (MAS) (from 12.5 to 80 mg/d). Treatment length ranged from one to 20 weeks. Eighteen studies were conducted in the USA and one study in Canada and the USA. Ten studies were conducted at multiple sites. Study funding was reported in all but two studies. Sixteen studies were funded by the manufacturer, and one was funded by government agencies. All amphetamines reduced the severity of ADHD symptoms as rated by patients. Lisdexamfetamine and MAS also reduced the severity of ADHD symptoms as rated by clinicians, but dexamphetamine did not. Overall, amphetamines did not make people more likely to stay in treatment and were associated with higher risk of treatment ending early as the result of adverse events. We found no evidence suggesting that higher doses worked better than lower ones. We did not find any difference in effectiveness between amphetamines that act for longer periods of time versus those that act for shorter periods of time. Therefore, it appears that short-term treatment with amphetamines reduces the severity of ADHD symptoms, but studies assessing the effects of amphetamines for longer periods of time are needed. We found no differences in effectiveness between amphetamines and guanfacine, modafinil, or paroxetine. The quality of the evidence was low to very low for all outcomes for several reasons, namely, it was possible for patients to know the treatment they were taking; the number of studies and included patients was low, leading to imprecise results for many outcomes; the studies had problems in their design; and, for some outcomes, results varied across trials."
    },
    {
        "index": "cochrane-simplification-test-42",
        "sentence": "We included six new studies (517 participants) in this review update, bringing the total of included studies to 10 (811 participants). The studies were heterogeneous with regard to study quality, the chronic painful conditions that were investigated, the dose of vitamin D given, co-interventions, and the outcome measures reported. Only two studies reported responder pain outcomes; the other studies reported treatment group average outcomes only. Overall, there was no consistent pattern that vitamin D treatment was associated with greater efficacy than placebo in any chronic painful condition (low quality evidence). Adverse events and withdrawals were comparatively infrequent, with no consistent difference between vitamin D and placebo (good quality evidence). The evidence addressing the use of vitamin D for chronic pain now contains more than twice as many studies and participants than were included in the original version of this review. Based on this evidence, a large beneficial effect of vitamin D across different chronic painful conditions is unlikely. Whether vitamin D can have beneficial effects in specific chronic painful conditions needs further investigation.",
        "gold": "We searched scientific databases for studies comparing vitamin D supplementation with placebo (a dummy treatment) or active medicines for the treatment of chronic painful conditions in adults. The evidence is current to February 2015. There is a small amount of evidence supporting this link but it is not of high quality and may not be reliable. This update of a review sought high quality evidence from randomised controlled trials (studies where participants are randomly allocated to receive one of several treatments) on vitamin D for chronic painful conditions. We found no consistent pattern that vitamin D treatment was better than placebo for any chronic painful condition, but the studies had methodological shortcomings (low quality evidence). More research is needed to determine if vitamin D is a useful pain treatment in any particular chronic painful condition. That research should examine whether any effect is restricted to people who are vitamin D deficient. It should also examine how much vitamin D is required, and for how long, before beneficial effects occur."
    },
    {
        "index": "cochrane-simplification-test-43",
        "sentence": "Forty-one studies were included involving more than 200 practices and 48,000 patients. Twenty-seven studies were RCTs, 12 were CBAs, and two were ITS. The studies were heterogeneous in terms of interventions, participants, settings and outcomes. The methodological quality of the studies was often poor. In all studies the intervention strategy was multifaceted. In 12 studies the interventions were targeted at health professionals, in nine they were targeted at the organisation of care, and 20 studies targeted both. In 15 studies patient education was added to the professional and organisational interventions. A combination of professional interventions improved process outcomes. The effect on patient outcomes remained less clear as these were rarely assessed. Arrangements for follow-up (organisational intervention) also showed a favourable effect on process outcomes. Multiple interventions in which patient education was added or in which the role of the nurse was enhanced also reported favourable effects on patients' health outcomes. Multifaceted professional interventions can enhance the performance of health professionals in managing patients with diabetes. Organisational interventions that improve regular prompted recall and review of patients (central computerised tracking systems or nurses who regularly contact the patient) can also improve diabetes management. The addition of patient-oriented interventions can lead to improved patient health outcomes. Nurses can play an important role in patient-oriented interventions, through patient education or facilitating adherence to treatment.",
        "gold": "This review examined the effects of interventions targeting health professionals or the way care is organised, with the aim of improving the management of people with diabetes in primary care, outpatient and community settings. The review found that multifaceted professional interventions (for example combinations of postgraduate education, reminders, audit and feedback, local consensus processes, and peer review) could enhance the performance of care providers. Organisational interventions that increased structured recall, such as central computerised tracking systems or nurses who regularly contacted patients, could also lead to improved care for patients with diabetes. The effectiveness of these interventions on patient outcomes (glycaemic control, cardiovascular risk factors, wellbeing) is less clear."
    },
    {
        "index": "cochrane-simplification-test-44",
        "sentence": "Five trials met the inclusion criteria. The studies included a total of 1503 women, with a mean of 301 participants. The trials compared the following contraceptives: combined oral contraceptive (COC) versus transdermal contraceptive patch, vaginal contraceptive ring, or levonorgestrel intrauterine system 20 \u00b5g/day (LNG-IUS 20); LNG-IUS 12 \u00b5g/day (LNG-IUS 12) versus LNG-IUS 16 \u00b5g/day (LNG-IUS 16); and LNG-IUS 20 versus the copper T380A intrauterine device (IUD). In the trials comparing two different types of methods, the study arms did not differ significantly for contraceptive efficacy or continuation. The sample sizes were small for two of those studies. The only significant outcome was that a COC group had a higher proportion of women who discontinued for 'other personal reasons' compared with the group assigned to the LNG-IUS 20 (OR 0.27, 95% CI 0.09 to 0.85), which may have little clinic relevance. The trial comparing LNG-IUS 12 versus LNG-IUS 16 showed similar efficacy over one and three years. In three trials that examined different LNG-IUS, continuation was at least 75% at 6 to 36 months. We considered the overall quality of evidence to be moderate to low. Limitations were due to trial design or limited reporting. Different doses in the LNG-IUS did not appear to influence efficacy over three years. In another study, continuation of the LNG-IUS appeared at least as high as that for the COC. The current evidence was insufficient to compare efficacy and continuation rates for hormonal and intrauterine contraceptive methods in women aged 25 years and younger.",
        "gold": "We searched for randomized trials of birth control methods until August 2015. Randomized trials are clinical studies in which people are randomly put into one of two or more treatment groups. Women in these studies were 25 years old or younger. The birth control methods could be either hormonal or a non-hormonal device placed in the uterus. The hormonal methods included pills, vaginal rings, or implants. The methods that are placed in the uterus include the intrauterine device (IUD) without hormones and the intrauterine system that has the hormone levonorgestrel (LNG-IUS). IUDs and the LNG-IUS are sometimes called intrauterine contraception (IUC). We found five trials that enrolled had a total of 1503 women. Some studies looked at different types of IUC, while others compared pills versus a vaginal ring, skin patch, or IUC. No study showed any major difference between the groups in pregnancy or continued use. Some of the trials were too small to find a difference. Women kept using IUC at least as long as pills in one study. IUC may be useful for women in this age group. Studies of different birth control with more women would help determine which methods work the best for young women. Overall, the quality of the results was moderate to low."
    },
    {
        "index": "cochrane-simplification-test-45",
        "sentence": "Eighty-eight trials were included (13 new trials). There were 42 trials of immunotherapy for house mite allergy; 27 pollen allergy trials; 10 animal dander allergy trials; two Cladosporium mould allergy, two latex and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 16 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication, and improvement in bronchial hyper-reactivity following immunotherapy.\u00a0There was a significant improvement in asthma symptom scores (standardised mean difference -0.59, 95% confidence interval -0.83 to -0.35) and it would have been necessary to treat three patients (95% CI 3 to 5) with immunotherapy to avoid one deterioration in asthma symptoms.\u00a0Overall it would have been necessary to treat four patients (95% CI 3 to 6) with immunotherapy to avoid one requiring increased medication. Allergen immunotherapy significantly reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. If 16 patients were treated with immunotherapy, one would be expected to develop a local adverse reaction.\u00a0If nine patients were treated with immunotherapy, one would be expected to develop a systemic reaction (of any severity). Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity.\u00a0 One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered.",
        "gold": "The review of trials found that immunotherapy can reduce asthma symptoms, the need for medications and the risk of severe asthma attacks after future exposure to the allergen. It is possibly as effective as inhaled steroids. However, there is an increased risk of a lump at the injection site, rash, wheezing, breathlessness and very rarely a fatal allergic reaction."
    },
    {
        "index": "cochrane-simplification-test-46",
        "sentence": "We did not find any new study which were eligible for inclusion in this update. The total number of studies remained unchanged, six trials involving 1297 patients. Five trials had a low risk of bias. One trial had an unclear risk of bias. Mortality at day 28 was significantly reduced by lung-protective ventilation with a relative risk (RR) of 0.74 (95% confidence interval (CI) 0.61 to 0.88); hospital mortality was reduced with a RR of 0.80 (95% CI 0.69 to 0.92). Overall mortality was not significantly different if a plateau pressure less than or equal to 31 cm H2O in the control group was used (RR 1.13, 95% CI 0.88 to 1.45). There was insufficient evidence for morbidity and long-term outcomes. Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials, makes the interpretation of the combined results difficult. Mortality was significantly reduced at day 28 and at the end of the hospital stay. The effects on long-term mortality are unknown, although the possibility of a clinically relevant benefit cannot be excluded. Ventilation with lower tidal volumes is becoming a routine strategy of treatment of acute respiratory distress syndrome and acute lung injury, stopping investigators from carrying out additional trials.",
        "gold": "Several studies have suggested that mechanical breathing can also cause lung damage and bleeding. A new lung protective way of mechanical ventilation was tested in large studies. In this third update of the Cochrane review we searched the databases until September 2012 but we did not find any new study which was eligible for inclusion. The total number of studies remained unchanged, six trials involving 1297 people. This systematic review shows that a gentler form of mechanical breathing (so-called protective ventilation) can decrease deaths in the short term, by 26% on average, but the effects in the long term are uncertain or unknown."
    },
    {
        "index": "cochrane-simplification-test-47",
        "sentence": "We included 15 RCTs with 1833 participants. We determined that none of the RCTs were of high methodological quality. For our primary outcomes, pooled results from two trials suggest that time to emergence from anaesthesia, that is, time needed to follow verbal commands, was longer with isoflurane than with propofol (mean difference (MD) -3.29 minutes, 95% confidence interval (CI) -5.41 to -1.18, low-quality evidence), and time to emergence from anaesthesia was not different with sevoflurane compared with propofol (MD 0.28 minutes slower with sevoflurane, 95% CI -0.56 to 1.12, four studies, low-quality evidence). Pooled analyses for adverse events suggest lower risk of nausea and vomiting with propofol than with sevoflurane (risk ratio (RR) 0.68, 95% CI 0.51 to 0.91, low-quality evidence) or isoflurane (RR 0.45, 95% CI 0.26 to 0.78) and greater risk of haemodynamic changes with propofol than with sevoflurane (RR 1.85, 95% CI 1.07 to 3.17), but no differences in the risk of shivering or pain. Pooled analyses for brain relaxation suggest lower risk of tense brain with propofol than with isoflurane (RR 0.88, 95% CI 0.67 to 1.17, low-quality evidence), but no difference when propofol is compared with sevoflurane. The finding of our review is that the intravenous technique is comparable with the inhalational technique of using sevoflurane to provide early emergence from anaesthesia. Adverse events with both techniques are also comparable. However, we derived evidence of low quality from a limited number of studies. Use of isoflurane delays emergence from anaesthesia. These results should be interpreted with caution. Randomized controlled trials based on uniform and standard methods are needed. Researchers should follow proper methods of randomization and blinding, and trials should be adequately powered.",
        "gold": "The evidence is current to June 2014. We included studies with participants from all age groups except neonates (infants less than 28 days old) who received injectable or gas techniques of anaesthesia during surgery for brain tumour. We reran the searches for all databases in March 2016 and found two studies that are awaiting classification. We will deal with them when we update this review. We found 15 eligible studies with 1833 participants. These studies compared one injectable drug (propofol) with two gaseous drugs (sevoflurane and isoflurane). Although isoflurane was associated with slower awakening (about three and a half minutes) compared with propofol, researchers found no important differences between propofol and sevoflurane. In terms of adverse effects, propofol was less likely to cause nausea and vomiting than either gas anaesthetic (about half as likely) but was more likely to be associated with changes in blood pressure. Overall, we found that isoflurane is associated with slower awakening, but we have found no evidence of important differences between sevoflurane and propofol. We found evidence of low quality for our main outcome of quick wakefulness, and the effect of injectable anaesthetic technique in people undergoing brain tumour surgery is uncertain. Further research and well-designed studies are needed."
    },
    {
        "index": "cochrane-simplification-test-48",
        "sentence": "Four trials including 15,936 hypertensive subjects were identified. Average age was 75.4 years. Mean blood pressure at entry across the studies was 171/86 mmHg. The combined result of the four trials reporting incidence of dementia indicated no significant difference between treatment and placebo (236/7767 versus 259/7660, Odds Ratio (OR) = 0.89, 95% CI 0.74, 1.07) and there was considerable heterogeneity between the trials. The combined results from the three trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.42, 95% CI 0.30, 0.53). Both systolic and diastolic blood pressure levels were reduced significantly in the three trials assessing this outcome (WMD = -10.22, 95% CI -10.78, -9.66 for systolic blood pressure, WMD = -4.28, 95% CI -4.58, -3.98 for diastolic blood pressure).  Three trials reported adverse effects requiring discontinuation of treatment and the combined results indicated no significant difference (OR = 1.01, 95% CI 0.92, 1.11). When analysed separately, however, more patients on placebo in Syst Eur 1997 were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the four studies.  Analysis of the included studies in this review was problematic as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen. There is no convincing evidence from the trials identified that blood pressure lowering in late-life prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients who received active treatment. This introduced bias. More robust results may be obtained by conducting a meta-analysis using individual patient data.",
        "gold": "We found four trials suitable for analysing the effectiveness of blood pressure lowering for preventing development of cognitive impairment and dementia. However, for several reasons, including the differing methodologies of the trials, the number of drop-outs from the trials, and active treatment of subjects in the control groups, we were unable to assess definitively the effectiveness of antihypertensive treatments for preventing cognitive impairment and dementia in people with no evidence of previous cerebrovascular disease."
    },
    {
        "index": "cochrane-simplification-test-49",
        "sentence": "We included 12 trials enrolling 3474 patients.\u00a0The overall risk of bias was unclear for the majority of articles due to a lack of reported data; however, the authors determined that this would be unlikely to impact negatively as most data outcomes were objective (e.g. death vs. no death). There was no evidence of the effectiveness in improving patient outcomes of PTCRA in non-complex lesions.\u00a0In complex lesions, there were no statistically significant differences in re-stenosis rates at six months (RR 1.05; 95% confidence interval (CI) 0.83 to 1.33) and at one year (RR 1.21; 95% CI 0.95 to 1.55) in those receiving PTCRA with adjunctive balloon angioplasty (PTCA) (PTCRA/PTCA) compared to those receiving PTCA alone. Morphological characteristics distinguishing complex lesions have not been examined in parallel-arm randomised controlled trials. The evidence for the effectiveness of PTCRA in in-stent re-stenosis is unclear Compared to angioplasty alone, PTCRA/PTCA did not result in a statistically significant increase in the risk of major adverse cardiac events (myocardial infarction (MI), emergency cardiac surgery or death) during the in-hospital period (RR 1.27; 95% CI 0.86 to 1.90). Compared to angioplasty, PTCRA was associated with nine times the risk of an angiographically detectable vascular spasm (RR 9.23; 95% CI 4.61 to 18.47), four times the risk of perforation (RR 4.28; 95% CI 0.92 to 19.83) and about twice the risk of transient vessel occlusions (RR 2.49; 95% CI 1.25 to 4.99) while angiographic dissections (RR 0.48; 95% CI 0.34 to 0.68) and stents used as a bailout procedure (RR 0.29; 95% CI 0.09 to 0.87) were less common. When conventional PTCA is feasible, PTCRA appears to confer no additional benefits. There is limited published evidence and no long-term data to support the routine use of PTCRA in in-stent re-stenosis. Compared to angioplasty alone, PTCRA/PTCA did not result in a higher incidence of major adverse cardiac events, but patients were more likely to experience vascular spasm, perforation and transient vessel occlusion. In certain circumstances (e.g. patients ineligible for cardiac surgery, those with architecturally complex lesions, or those with lesions that fail PTCA), PTCRA may achieve satisfactory re-vascularisation in subsequent procedures.",
        "gold": "This review sought to determine whether PTCRA leads to improved patient outcomes compared to balloon angioplasty. It was important to do this review as it is not known whether or not PTCRA provides greater benefits to patients compared to balloon angioplasty. The review analysed data from 12 studies, which showed that there is limited evidence to support the routine use of PTCRA for in-stent re-stenosis; however, only for those people who were not suitable for surgery. For those with complex lesions, PTCRA may provide some benefit in comparison to balloon angioplasty. The review also showed that patients receiving PTCRA were more likely to have perforations during the procedure compared to patients receiving balloon angioplasty. This review was limited by the small number of studies and deficiency of data reported in some of the studies."
    },
    {
        "index": "cochrane-simplification-test-50",
        "sentence": "Three RCTs (333 participants) were identified, two of which were multicentre trials comprising only participants positive for respiratory syncytial virus (RSV). The other trial enrolled participants clinically diagnosed with bronchiolitis from a hospital in Italy. All studies used 2.5 mL (1 mg/mL) of nebulised rhDNase compared with placebo either as a daily or a twice daily dose. Adjunctive therapy included nebulised salbutamol, steroids, supplemental oxygen, intravenous fluids or tube feeding, nasal washing, nasal decongestants and antibiotics. Overall, nebulised rhDNase showed no benefit in clinically meaningful outcomes. Meta-analysis favoured the control group with a shorter duration of hospital stay (MD 0.50; 95% CI 0.10 to 0.90, P = 0.01) and better clinical score improvement (SMD -0.24; 95% CI -0.50 to 0.01, P = 0.06). The largest trial showed no difference in supplemental oxygen use or intensive care unit (ICU) admission. In one RCT, four out of 11 patients in the treatment group had atelectasis. Two of these patients showed distinctive clinical improvement after nebulised rhDNase. There was no significant difference in adverse events. These included temporary desaturation, temporary coughing, increased coughing, facial rash, hoarseness, dyspnoea and bad taste, reported in a total of 11 patients from both treatment groups. The results based on the three included studies in this review did not support the use of nebulised rhDNase in children under 24 months of age hospitalised with acute bronchiolitis. In these patients, treatment did not shorten the length of hospitalisation or improve clinical outcomes. It might have a role in severe bronchiolitis complicated by atelectasis, but further clinical studies would need to be performed.",
        "gold": "We identified three randomised controlled trials involving 333 children up to 24 months of age hospitalised with bronchiolitis. All three studies compared nebulised rhDNase with placebo. Any additional treatments were given to both groups. Overall, the studies did not show that nebulised rhDNase shortened the duration of hospital admission, or improved the severity of symptoms. No serious side effects were reported by any of the studies. One study showed that in patients suffering from atelectasis, a severe complication of bronchiolitis wherein the lung does not expand completely, nebulised rhDNase treatment resulted in a distinct improvement within two days. To confirm this beneficial effect, further clinical studies in patients with severe bronchiolitis are needed. Currently, the use of this treatment in young children hospitalised with bronchiolitis is not recommended."
    },
    {
        "index": "cochrane-simplification-test-51",
        "sentence": "Two studies with a total of 181 participants met the inclusion criteria, 116 undergoing the percutaneous technique and 65 treated by cut-down femoral artery access. One study had a small sample size and did not adequately report method of randomisation, allocation concealment or pre-selected outcomes. The second study was a larger study with few sources of bias and good methodology. We observed no significant difference in mortality between groups, with only one mortality occurring overall, in the totally percutaneous group (risk ratio (RR) 1.50; 95% confidence interval (CI) 0.06 to 36.18; 181 participants; moderate-quality evidence). Only one study reported aneurysm exclusion. In this study we observed only one failure of aneurysm exclusion in the surgical cut-down femoral artery access group (RR 0.17, 95% CI 0.01 to 4.02; 151 participants; moderate-quality evidence). No wound infections occurred in the cut-down femoral artery access group or the percutaneous group across either study (moderate-quality evidence). There was no difference in major complication rate between cut-down femoral artery access and percutaneous groups (RR 0.91, 95% CI 0.20 to 1.68; 181 participants; moderate-quality evidence); or in bleeding complications and haematoma (RR 0.94, 95% CI 0.31 to 2.82; 181 participants; high-quality evidence). Only one study reported long-term complication rates at six months, with no differences between the percutaneous and cut-down femoral artery access group (RR 1.03, 95% CI 0.34 to 3.15; 134 participants; moderate-quality evidence). We detected differences in surgery time, with percutaneous approach being significantly faster than cut-down femoral artery access (mean difference (MD) -31.46 minutes; 95% CI -47.51 minutes to -15.42 minutes; 181 participants; moderate-quality evidence). Only one study reported duration of ITU (intensive treatment unit) and hospital stay, with no difference found between groups. This review shows moderate-quality evidence of no difference between the percutaneous approach compared with cut-down femoral artery access group for short-term mortality, aneurysm exclusion, major complications, wound infection and long-term (six month) complications, and high-quality evidence for no difference in bleeding complications and haematoma. There was a difference in operating time, with moderate-quality evidence showing that the percutaneous approach was faster than the cut-down femoral artery access technique. We downgraded the quality of the evidence to moderate as a result of the limited number of studies, low event numbers and imprecision. As the number of included studies were limited, further research into this technique would be beneficial. The search identified one ongoing study, which may provide an improved evidence base in the future.",
        "gold": "This update found two studies comparing the cut-down artery access with the percutaneous technique (current to October 2016). One was a small study with 30 participants, the other a larger more robust study with 151 participants. The large study was found to be of high quality with little risk of bias. The smaller study did not report on the methods of randomisation, how the randomisation was concealed and the pre-selected outcomes of interest. Combined, the studies had 181 participants; 116 underwent the cut-down technique and 65 the percutaneous technique. Both studies compared rates of death, major complications, wound infections, bleeding complications, and length of the operation. Overall, we did not find any difference in the rates of death (moderate-quality evidence), major complications (moderate-quality evidence); or bleeding complications between the percutaneous and cut-down techniques (high-quality evidence). No one developed a wound infection (moderate-quality evidence). The surgery took less time (moderate-quality evidence) in the percutaneous group compared with the cut-down group. Only one study reported if the aneurysm wall was successfully reinforced (checked by a CT scan, moderate-quality evidence), on complications at six months, (moderate-quality evidence); and on how long participants spent in an intensive treatment unit (ITU). We did not find any difference between the cut-down and percutaneous groups. This review shows moderate-quality evidence of no difference between the percutaneous approach compared with cut-down femoral artery access group for short-term mortality, aneurysm exclusion (sealing of the aneurysms), major complications, wound infection and long-term (six months) complications; and high-quality evidence for no difference in bleeding complications. There was a difference in operating time, with moderate-quality evidence showing that the percutaneous approach was faster than the cut-down femoral artery access technique. We downgraded the quality of the evidence to moderate due to the small number of studies, overall event rates and imprecision (differences around the level of effect)."
    },
    {
        "index": "cochrane-simplification-test-52",
        "sentence": "Two trials met the inclusion criteria. The sponge was significantly less effective in both trials in preventing overall pregnancy than was the diaphragm. In the larger USA trial, the 12-month cumulative life-table termination rates per 100 women for overall pregnancy were 17.4 for the sponge and 12.8 for the diaphragm. The rates were 24.5 for the sponge and 10.9 for the diaphragm in the UK trial. Similarly, discontinuation rates at 12 months were higher with the sponge than with the diaphragm (Odds ratio 1.31; 95% CI 1.07 to 1.59). Allergic-type reactions were more common with the sponge, although discontinuation for discomfort differed in the two trials. No new trials have been identified since the initial review. The sponge was less effective than the diaphragm in preventing pregnancy. Discontinuation rates were higher at 12 months as well. Other randomized controlled trials will be needed to resolve the potential role of spermicides in preventing sexually transmitted infections or in causing adverse effects.",
        "gold": "In April 2013, we did computer searches for randomized trials that compared the sponge with the diaphragm. For the original review, we looked at reference lists and book chapters to find trials. We also wrote to researchers to look for more trials. We found two trials. In a large USA trial, the sponge did not work as well as the diaphragm in preventing pregnancy. For every 100 women who used the sponge for a year, about 17 got pregnant. Of those who used the diaphragm, 13 became pregnant. A U.K. trial found similar results. For each 100 women who used the sponge for a year, about 25 got pregnant. Of the diaphragm users, 11 became pregnant. We have not found any new trials since the initial review. About 30% more women stopped using the sponge than the diaphragm. Allergy to the sponge was a problem for some women. However, discomfort caused about the same numbers of women to stop using their birth control method."
    },
    {
        "index": "cochrane-simplification-test-53",
        "sentence": "Sixteen studies were identified for possible inclusion in the review, six of which were included. Three studies investigated prevention and three studies investigated amelioration. Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible. Two studies investigated a pharmacological intervention for the prevention of cognitive deficits; memantine compared with placebo, and d-threo-methylphenidate HCL compared with placebo. In the first study the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The second study found no statistically significant difference between arms, with few adverse events. The third study investigated a rehabilitation program for the prevention of cognitive deficits but did not carry out a statistical comparison of cognitive performance between groups. Three studies investigated the use of a pharmacological intervention for the treatment of cognitive deficits; methylphenidate compared with modafinil, two different doses of modafinil, and donepezil compared with placebo. The first study found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. The second study combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The third study did not find an improvement in the primary cognitive outcome of overall performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. No non-pharmacological studies for the amelioration of cognitive deficits were eligible. There were a number of limitations across studies but few without high risks of bias. There is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil may have a role in treating cognitive deficits in adults with primary or metastatic brain tumours who have been treated with cranial irradiation. Patient withdrawal affected the statistical power of both studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher quality of evidence. There is no strong evidence to support any non-pharmacological interventions (medical or cognitive/behavioural) in the prevention or amelioration of cognitive deficits. Non-randomised studies appear promising but are as yet to be conclusive via translation into high quality evidence. Further research is required.",
        "gold": "In August 2014 we searched four literature databases. Six randomised controlled trials (RCTs), in which patients were randomly assigned to the intervention or a comparison group (control group), were eligible for inclusion. Each trial assessed different interventions, so results were not combined. The largest trial investigated the medical drug memantine in 508 patients with a metastatic brain tumour. Another trial investigated donepezil in 198 patients with a primary or secondary brain tumour. The other trials were smaller and investigated modafinil and methylphenidate. We found one psychological intervention for preventing cognitive deficits during brain radiation. There is one ongoing medical drug trial recruiting participants. There were many non-randomised and non-controlled trials that offer promising results for further exploration using an RCT method. Findings into the efficacy of memantine offer supportive evidence for preventing cognitive deficits in patients with a secondary brain tumour receiving brain irradiation. Findings into the efficacy of donepezil offer some support for its use in the amelioration of cognitive deficits in patients with a primary or secondary tumour previously treated with radiation. The remaining studies did not have a sufficient number of participants to provide reliable results. The drugs used had few side effects (adverse events), although these were not reported well. Recruitment and retention of trial participants for these medical drug studies is difficult. We found limitations in the evidence across studies, most medical drug randomised controlled trials had a low risk of bias, whereas the psychological interventions were at a high risk of bias."
    },
    {
        "index": "cochrane-simplification-test-54",
        "sentence": "Two studies assessed as at high risk of bias, reporting data from 26 analysed participants were included in this review. The age range of participants was from 17 to 55 years. Both trials investigated the effectiveness of low-level laser treatment compared to placebo laser therapy on inferior alveolar sensory deficit as a result of iatrogenic injury. Patient-reported altered sensation was partially reported in one study and fully reported in another. Following treatment with laser therapy, there was some evidence of an improvement in the subjective assessment of neurosensory deficit in the lip and chin areas compared to placebo, though the estimates were imprecise: a difference in mean change in neurosensory deficit of the chin of 8.40 cm (95% confidence interval (CI) 3.67 to 13.13) and a difference in mean change in neurosensory deficit of the lip of 21.79 cm (95% CI 5.29 to 38.29). The overall quality of the evidence for this outcome was very low; the outcome data were fully reported in one small study of 13 patients, with differential drop-out in the control group, and patients suffered only partial loss of sensation. No studies reported on the effects of the intervention on the remaining primary outcomes of pain, difficulty eating or speaking or taste. No studies reported on quality of life or adverse events. The overall quality of the evidence was very low as a result of limitations in the conduct and reporting of the studies, indirectness of the evidence and the imprecision of the results. There is clearly a need for randomised controlled clinical trials to investigate the effectiveness of surgical, medical and psychological interventions for iatrogenic inferior alveolar and lingual nerve injuries. Primary outcomes of this research should include: patient-focused morbidity measures including altered sensation and pain, pain, quantitative sensory testing and the effects of delayed treatment.",
        "gold": "The Cochrane Oral Health Group carried out this review, and the evidence is current as of 9 October 2013. There are two studies included, both published in 1996, which compared low-level laser treatment to placebo or fake treatment for partial loss of sensation following surgery to the lower jaw. There were 15 participants in one study and 16 in the other, their ages ranging from 17 to 55 years. All had suffered accidental damage to nerves of the lower jaw and tongue causing some loss of sensation following surgery. Low-level laser therapy was the only treatment to be evaluated in the included studies and this was compared to fake or placebo laser therapy. No studies were found that evaluated other surgical, medical or counselling treatments. There was some evidence of an improvement when participants reported whether or not sensation was better in the lip and chin areas with low-level laser therapy. This is based on the results of a single, small study, so the results should be interpreted with caution. No studies reported on the effects of the treatment on other outcomes such as pain, difficulty eating or speaking or taste. No studies reported on quality of life or harm. The overall quality of the evidence is very low as a result of limitations in the conduct and reporting of the two included studies and the low number of participants, and evidence from participants with only partial sensory loss."
    },
    {
        "index": "cochrane-simplification-test-55",
        "sentence": "Two trials (281 pregnancies and 282 fetuses) met our inclusion criteria. However, the two trials had significant clinical and methodological heterogeneity such that a meta-analysis combining trial data was considered inappropriate. One trial (involving 161 pregnancies) was based on women with a history of diabetes. It showed no statistically significant difference between using combined oestrogen and progestogen and using placebo for all our proposed primary outcomes, namely, miscarriage (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.32 to 2.80), perinatal death (RR 0.94, 95% CI 0.53 to 1.69) and preterm birth (less than 34 weeks of gestation) (RR 0.91, 95% CI 0.80 to 1.04). In terms of this review's secondary outcomes, use of combined oestrogen and progestogen was associated with an increased risk of maternal cancer in the reproductive system (RR 6.65, 95% CI 1.56 to 28.29). However, for the outcome of cancer other than that of the reproductive system in mothers, there was no difference between groups. Similarly, there were no differences between the combined oestrogen and progestogen group versus placebo for other secondary outcomes reported: low birthweight of less than 2500 g, genital abnormalities in the offspring, abnormalities other than genital tract in the offspring, cancer in the reproductive system in the offspring, or cancer other than of the reproductive system in the offspring. The second study was based on pregnant women who had undergone in-vitro fertilisation (IVF). This study showed no difference in the rate of miscarriage between the combined oestrogen and progesterone group and the no treatment group (RR 0.66, 95% CI 0.23 to 1.85). The study did not report on this review's other primary outcomes (perinatal death or rates of preterm birth), nor on any of our proposed secondary outcomes. There is an insufficient evidence from randomised controlled trials to assess the use of combined oestrogen and progesterone for preventing miscarriages. We strongly recommend further research in this area.",
        "gold": "The hormones oestrogen and progesterone have established physiological roles in maintaining pregnancy. It has been suggested that supplementation of these hormones could help prevent miscarriage before 24 weeks of pregnancy, particularly in women who have low levels of the hormones, in assisted reproductive technology programs, or who have a history of repeated miscarriages. In our review of randomised controlled trials published in major scientific databases, we only identified two trials that met our inclusion criteria. The two trials involved small numbers of women. One involved 161 women with diabetes who took oral placebo or oral diethylstilboestrol and ethisterone in increasing doses from before the end of the 16th week until birth. The other trial involved 120 women with pregnancy assisted by in vitro fertilisation and embryo transfer who continued treatment until the completed 12th week of gestation. From the little evidence available, the two trials found no evidence that combined oestrogen and progestogen can prevent miscarriage (progestogen is a major class of hormones which includes progesterone) when compared with placebo or usual care. The first of the two studies indicated an increased risk for the mothers who used hormonal therapy during pregnancy of developing cancer later in life. Diethylstilboestrol is no longer in use and poses serious adverse effects while ethisterone contains androgenic properties thought to be responsible for genital abnormalities and has been replaced by progesterone. Overall, we acknowledge the lack of trials, especially large-scale trials, and therefore suggest further research is needed in this area before supporting or disproving the use of combined oestrogen and progesterone for the prevention of miscarriages."
    },
    {
        "index": "cochrane-simplification-test-56",
        "sentence": "There were fourteen studies (16 comparisons) with extractable data included in the review, of which ten studies examined TCAs, two examined SSRIs and two included both classes, all compared with placebo. The number of participants in the intervention groups was 1364 and in the placebo groups 919. Nearly all studies were of short duration, typically 6-8 weeks. Pooled estimates of efficacy data showed an RR of 1.24, 95% CI 1.11-1.38 in favour of TCAs against placebo. For SSRIs this was 1.28, 95% CI 1.15 to 1.43.. The numbers needed to treat (NNT) for TCAs ranged from 7 to 16 {median NNT 9} patient expected event rate ranged from 63% to 26% respectively) and for SSRIs from 7 to 8 {median NNT 7} (patient expected event rate ranged from 48% to 42% respectively) . The numbers needed to harm (NNH for withdrawal due to side effects) ranged from 4 to 30 for TCAs (excluding three studies with no harmful events leading to withdrawal) and 20 to 90 for SSRIs. Both TCAs and SSRIs are effective for depression treated in primary care.",
        "gold": "However, most systematic reviews of antidepressant treatment have included trials conducted in secondary care settings. There has been doubt about the effectiveness of antidepressants in primary care, and hence the impetus to do this review. Through extensive searches of the literature we found 14 studies conducted in adults (not the elderly) in primary care setting, in which tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) were compared against a placebo control group in the treatment of depression. The results showed that both TCAs and SSRIs were effective for depression. Most of the studies were supported by funds from pharmaceutical companies and were of short duration. There appeared to be more adverse effects with TCAs than with SSRIs, however rates of withdrawal from study medication due to adverse effects were very similar between the two antidepressant classes. Adverse effects not leading to medication cessation seemed to be more common with TCAs than SSRIs."
    },
    {
        "index": "cochrane-simplification-test-57",
        "sentence": "No new studies were found for this update. Nine included studies (4373 participants, 5223 attacks) compared ibuprofen with placebo or other active comparators; none combined ibuprofen with a self-administered antiemetic. All studies treated attacks with single doses of medication. For ibuprofen 400 mg versus placebo, NNTs for 2-hour pain-free (26% versus 12% with placebo), 2-hour headache relief (57% versus 25%) and 24-hour sustained headache relief (45% versus 19%) were 7.2, 3.2 and 4.0, respectively. For ibuprofen 200 mg versus placebo, NNTs for 2-hour pain-free (20% versus 10%) and 2-hour headache relief (52% versus 37%) were 9.7 and 6.3, respectively. The higher dose was significantly better than the lower dose for 2-hour headache relief. Soluble formulations of ibuprofen 400 mg were better than standard tablets for 1-hour, but not 2-hour headache relief. Similar numbers of participants experienced adverse events, which were mostly mild and transient, with ibuprofen and placebo. Ibuprofen 400 mg did not differ from rofecoxib 25 mg for 2-hour headache relief or 24-hour headache relief. We found no new studies since the last version of this review. Ibuprofen is an effective treatment for acute migraine headaches, providing pain relief in about half of sufferers, but complete relief from pain and associated symptoms for only a minority. NNTs for all efficacy outcomes were better with 400 mg than 200 mg in comparisons with placebo, and soluble formulations provided more rapid relief. Adverse events were mostly mild and transient, occurring at the same rate as with placebo.",
        "gold": "This is an updated version of the original Cochrane review published in Issue 10, 2010 (Rabbie 2010); no new studies were found. A single oral dose of ibuprofen 200 mg or 400 mg is effective in relieving pain in migraine headaches. Pain will be reduced from moderate or severe to no pain by two hours in just over 1 in 4 people (26%) taking ibuprofen 400 mg, compared with about 1 in 10 (12%) taking placebo. It will be reduced from moderate or severe to no worse than mild pain by two hours in roughly 1 in 2 people (57%) taking ibuprofen compared with approximately 1 in 4 (25%) taking placebo. Of those who experience effective headache relief at two hours, more have that relief sustained over 24 hours with ibuprofen than with placebo. A 200-mg dose is slightly less effective, while soluble formulations give more rapid responses. A single 400-mg dose of ibuprofen has efficacy similar to that shown for a single dose of 1000 mg aspirin in a separate Cochrane review (Kirthi 2013). Adverse events are mostly mild and transient, occurring in the same proportion of participants treated with ibuprofen and placebo. Very few individuals had serious adverse events or needed to withdraw from these studies because of adverse events. There is no information for ibuprofen combined with a self-administered antiemetic, and little information comparing ibuprofen with other medications. There were no significant differences between ibuprofen 400 mg and rofecoxib 25 mg (now withdrawn) for 2-hour headache relief, 24-hour sustained headache relief, or use of rescue medication."
    },
    {
        "index": "cochrane-simplification-test-58",
        "sentence": "We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations.",
        "gold": "This review included 43 randomized controlled trials (3497 people with dry eye) that compared OTC artificial tears with other OTC artificial tears, with no treatment, or with placebo. We considered participant symptoms to be the primary outcome for this review. We recorded other commonly performed dry eye tests as secondary outcomes (e.g. vision, tear stability). We measured primary and secondary outcomes at two and four weeks, although we also considered other time points in this review. We searched for trials up to December 2015. This review analyzed many OTC artificial tear formulations, and most of the literature indicates uncertainty as to which OTC artificial tear works best. The literature also shows that OTC artificial tears may be effective at treating dry eye symptoms and that OTC artificial tears are generally safe, although not without side effects. We also identified an additional 18 potentially eligible trials that were registered, but did not provide any results or publications. These trials may have enrolled 2079 total participants for whom no data are available. Without the results of these trials, the effects of the OTC artificial tears that they evaluated are unknown. The overall quality of the evidence was low for the various OTC artificial tear formulations compared in this review. This finding indicates that future published research may have an important impact on the conclusions currently provided in this review."
    },
    {
        "index": "cochrane-simplification-test-59",
        "sentence": "One randomised trial in 136 patients studied maintaining lamivudine in second-line regimens or not. There was no difference in virological outcomes in the group who maintained lamivudine and those who did not in their subsequent regimens. Two other small observational studies reported in abstract form also did not report a difference in the proportion of those with viral suppression after six months and time to HIV-1 RNA suppression among those on a lamivudine (3TC) or emtricitabine (FTC) regimen compared to those on a 3TC/FTC-sparing second-line regimen. There were no trials identified comparing boosted protease inhibitors (PIs) or nucleoside backbone combinations after first-line failure on non-thymidine analog combinations. Observational studies of populations starting ART in resource-limited settings suggest that short-term response on boosted PI-based regimens is encouraging. There is limited evidence to evaluate second-line therapies in patients with HIV who fail first-line treatment with a WHO-recommended regimen. One randomised trial in 136 patients and two observational studies (both of low quality) suggest no difference in virological suppression whether or not lamivudine is maintained in a second-line regimen. While outcomes of second-line regimens with boosted PIs are favourable in general, there are no studies comparing boosted PIs directly in populations starting second-line regimens. Current recommendations are based on available resources and patient- and public-health-level considerations.",
        "gold": "This review attempted to assess the best ART regimen for HIV-infected people in low- and middle-income countries following treatment failure; however, the review found limited studies addressing this topic. One randomised trial and one abstract of an observational study evaluated whether or not to maintain lamivudine in second-line regimens; both suggested no difference in outcomes. There were no studies comparing boosted PI-containing second-line regimens in patients failing an NNRTI-based first-line regimen, nor any evaluating NRTI combinations after first-line with non-thymidine analog combinations. While such trials are difficult to conduct for a variety of reasons, randomised controlled trails comparing second-line therapies are needed, especially in resource-limited settings."
    },
    {
        "index": "cochrane-simplification-test-60",
        "sentence": "We included 133 (127 cohort type and 6 case-control) studies involving 844,206 participants. We evaluated a total of seven different prespecified index tests in the 133 studies, as well as 69 non-prespecified, and 32 combinations. For the prespecified index tests, we found six studies for the Mallampati test, 105 for the modified Mallampati test, six for the Wilson risk score, 52 for thyromental distance, 18 for sternomental distance, 34 for the mouth opening test, and 30 for the upper lip bite test. Difficult face mask ventilation was the reference standard in seven studies, difficult laryngoscopy in 92 studies, difficult tracheal intubation in 50 studies, and failed intubation in two studies. Across all studies, we judged the risk of bias to be variable for the different domains; we mostly observed low risk of bias for patient selection, flow and timing, and unclear risk of bias for reference standard and index test. Applicability concerns were generally low for all domains. For difficult laryngoscopy, the summary sensitivity ranged from 0.22 (95% confidence interval (CI) 0.13 to 0.33; mouth opening test) to 0.67 (95% CI 0.45 to 0.83; upper lip bite test) and the summary specificity ranged from 0.80 (95% CI 0.74 to 0.85; modified Mallampati test) to 0.95 (95% CI 0.88 to 0.98; Wilson risk score). The upper lip bite test for diagnosing difficult laryngoscopy provided the highest sensitivity compared to the other tests (P < 0.001). For difficult tracheal intubation, summary sensitivity ranged from 0.24 (95% CI 0.12 to 0.43; thyromental distance) to 0.51 (95% CI 0.40 to 0.61; modified Mallampati test) and the summary specificity ranged from 0.87 (95% CI 0.82 to 0.91; modified Mallampati test) to 0.93 (0.87 to 0.96; mouth opening test). The modified Mallampati test had the highest sensitivity for diagnosing difficult tracheal intubation compared to the other tests (P < 0.001). For difficult face mask ventilation, we could only estimate summary sensitivity (0.17, 95% CI 0.06 to 0.39) and specificity (0.90, 95% CI 0.81 to 0.95) for the modified Mallampati test. Bedside airway examination tests, for assessing the physical status of the airway in adults with no apparent anatomical airway abnormalities, are designed as screening tests. Screening tests are expected to have high sensitivities. We found that all investigated index tests had relatively low sensitivities with high variability. In contrast, specificities were consistently and markedly higher than sensitivities across all tests. The standard bedside airway examination tests should be interpreted with caution, as they do not appear to be good screening tests. Among the tests we examined, the upper lip bite test showed the most favourable diagnostic test accuracy properties. Given the paucity of available data, future research is needed to develop tests with high sensitivities to make them useful, and to consider their use for screening difficult face mask ventilation and failed intubation. The 27 studies in 'Studies awaiting classification' may alter the conclusions of the review, once we have assessed them.",
        "gold": "We included 133 studies (844,206 participants) which investigated the accuracy of the seven tests above, plus 69 other common tests and 32 test combinations, in detection of difficult airways. For difficult laryngoscopy, the average sensitivity (percentage of correctly identified difficult airways) ranged from 22% (mouth opening test) to 63% (upper lip bite test). The average specificity (percentage of correctly classified patients without difficult airways) ranged from 80% (modified Mallampati test) to 95% (Wilson risk score). The upper lip bite test had the highest sensitivity of all tests considered. For difficult tube insertion, the average sensitivity ranged from 24% (thyromental distance) to 51% (modified Mallampati test) and the average specificity ranged from 87% (modified Mallampati test) to 93% (mouth opening test). The modified Mallampati test had the highest sensitivity of all tests considered. For difficult face mask ventilation (another indication of a difficult airway), there were only enough data to calculate average sensitivity of 17% and specificity 90% for the modified Mallampati test. Overall, the evidence from the studies was of moderate to high quality. The likelihood of the studies providing reliable results was generally high, although in half of them, the intubating physician knew the result of the preceding test, which may have influenced results, but this is the normal situation in routine clinical care. The characteristics of patients, tests, and conditions were comparable to those seen in a wide range of everyday clinical settings. The results of this review should apply to standard preoperative airway assessments in apparently normal hospital patients worldwide. The bedside screening tests examined in this review are not well suited for the purpose of detecting unanticipated difficult airways because they missed a large number of people who had a difficult airway."
    },
    {
        "index": "cochrane-simplification-test-61",
        "sentence": "Sixty-three studies met the inclusion criteria with a total of 8014 participants. Of these, 56 trials recruited infants and young children. The trials varied in the definition used for acute diarrhoea and the end of the diarrhoeal illness, as well as in the risk of bias. The trials were undertaken in a wide range of different settings and also varied greatly in organisms tested, dosage, and participants' characteristics. No adverse events were attributed to the probiotic intervention. Probiotics reduced the duration of diarrhoea, although the size of the effect varied considerably between studies. The average of the effect was significant for mean duration of diarrhoea (mean difference 24.76 hours; 95% confidence interval 15.9 to 33.6 hours; n=4555, trials=35) diarrhoea lasting \u22654 days (risk ratio 0.41; 0.32 to 0.53; n=2853, trials=29) and stool frequency on day 2 (mean difference 0.80; 0.45 to 1.14; n=2751, trials=20). The differences in effect size between studies was not explained by study quality, probiotic strain, the number of different strains, the viability of the organisms, dosage of organisms, the causes of diarrhoea, or the severity of the diarrhoea, or whether the studies were done in developed or developing countries. Used alongside rehydration therapy, probiotics appear to be safe and have clear beneficial effects in shortening the duration and reducing stool frequency in acute infectious diarrhoea. However, more research is needed to guide the use of particular probiotic regimens in specific patient groups.",
        "gold": "A number of randomized controlled trials have been done to see whether probiotics are beneficial in acute infectious diarrhoea. We have searched for as many of these trials as possible and collected together the data in a systematic way to try to discover whether or not probiotics are beneficial in acute diarrhoea. We identified 63 trials, which included a total of 8014 people - mainly infants and children. Probiotics were not associated with any adverse effects. Nearly all studies reported a shortened duration of diarrhoea and reduced stool frequency in people who received probiotics compared to the controls. Overall, probiotics reduced the duration of diarrhoea by around 25 hours, the risk of diarrhoea lasting four or more days by 59% and resulted in about one fewer diarrhoeal stool on day 2 after the intervention. However, there was very marked variability in the study findings and so these estimates are approximate. We concluded that these results were very encouraging but more research is needed to identify exactly which probiotics should be used for which groups of people, and also to assess the cost effectiveness of this treatment."
    },
    {
        "index": "cochrane-simplification-test-62",
        "sentence": "We included only one study that compared nidotherapy-enhanced standard care with standard care alone (total 52 participants); this study was classified by its authors as a 'pilot study'. The duration of the included study was 18 months in total. The single study examined the short-term (up to six months) and medium-term (between six and 12 months) effects of nidotherapy-enhanced standard care versus standard care. Nidotherapy-enhanced standard care was favoured over standard care for social functioning in both the short term (n = 50, 1 RCT, MD -2.10, 95% CI -4.66 to 0.46) and medium term (n = 37, 1 RCT, MD -1.70, 95% CI -4.60 to 1.20, Very low quality); however, these results did not reach statistical significance. Results concerning engagement with non-inpatient services favoured the intervention group in both the short term (n = 50, 1 RCT, MD 2.00, 95% CI 0.13 to 3.87) and medium term (n = 37, 1 RCT, MD 1.70, 95% CI -0.09 to 3.49), with statistical significance evident in the short term, but not in the medium term. Results of people leaving the study early favoured the intervention in the short term (n = 52, 1 RCT, RR 0.86, 95% CI 0.06 to 12.98), with slight favour of the control group at medium term (n = 50, 1 RCT, RR 0.99, 95% CI 0.39 to 2.54); again, these results did not reach statistical significance. Results for the adverse effects/events of death (measured by 12 months) favoured the intervention (n = 52, 1 RCT, RR 0.29, 95% CI 0.01 to 6.74, Very low quality) but with no statistical significance. Skewed results were available for mental state, service use, and economic outcomes, and present a mixed picture of the benefits of nidotherapy. Further research is needed into the possible benefits or harms of this newly-formulated therapy. Until such research is available, patients, clinicians, managers and policymakers should consider it an experimental approach.",
        "gold": "This review includes one small pilot study with 52 participants. The study compared nidotherapy with standard care versus standard care alone and lasted 18 months.\u00a0Findings suggest some limited evidence that those who received nidotherapy might experience a slight improvement in social functioning or personal relationships, mental state and may spend less time as inpatients in hospital over the course of 12 months, but there is no information concerning the appropriateness of this for the individual.\u00a0However, these limited findings need to be treated with considerable caution. The degree of any possible improvements that come from taking part in nidotherapy remain unclear due to the single study\u2019s small sample size, incomplete evidence and risk of bias.\u00a0No evidence is available on the effect of nidotherapy on general functioning, quality of life, taking medication, satisfaction with treatment, employment status or adverse effects. Further research is required to fill this gap in knowledge about the effectiveness, benefits and possible hazards of nidotherapy.\u00a0Until such a time, people with mental health problems, health professionals, managers and policymakers should consider this new therapy an experimental one. This summary has been written by a consumer Ben Gray (Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness. Email: [email\u00a0protected])."
    },
    {
        "index": "cochrane-simplification-test-63",
        "sentence": "Our searches identified two new published studies with classic design, and one new published study with an enriched enrolment randomised withdrawal (EERW) design. We included eight studies. Five (3283 participants) had a classic design in which participants were randomised at the start of the study to pregabalin (150, 300, 450, or 600 mg daily) or placebo, with assessment after 8 to 13 weeks of stable treatment. No studies included active comparators. Studies had low risk of bias, except that the last observation carried forward (LOCF) imputation method used in analyses of the primary outcomes could overestimate treatment effect. Pregabalin increased the number of participants experiencing substantial benefit (at least 50% pain intensity reduction after 12 or 13 weeks' stable treatment (450 mg: RR 1.8, 95% CI 1.4 to 2.1, 1874 participants, 5 studies, high quality evidence)). Substantial benefit with pregabalin 300 to 600 mg was experienced by about 14% of participants with placebo, but about 9% more with pregabalin 300 to 600 mg (22% to 24%) (high quality evidence). Pregabalin increased the number of participants experiencing moderate benefit (at least 30% pain intensity reduction after 12 or 13 weeks' stable treatment) (450 mg: RR 1.5, 95% CI (1.3 to 1.7), 1874 participants, 5 studies, high quality evidence). Moderate benefit with pregabalin 300 to 600 mg was experienced by about 28% of participants with placebo, but about 11% more with pregabalin 300 to 600 mg (39% to 43%) (high quality evidence). A similar magnitude of effect was found using PGIC of 'very much improved' and 'much or very much improved'. NNTs for these outcomes ranged between 7 and 14 (high quality evidence). A small study (177 participants) compared nightly with twice-daily pregabalin, and concluded there was no difference in effect. Two studies (1492 participants began initial dose titration, 687 participants randomised) had an EERW design in which those with good pain relief after titration were randomised, double blind, to continuing the effective dose (300 to 600 mg pregabalin daily) or a short down-titration to placebo for 13 or 26 weeks. We calculated the outcome of maintained therapeutic response (MTR) without withdrawal, equivalent to a moderate benefit. Of those randomised, 40% had MTR with pregabalin and 20% with placebo (high quality evidence). The NNT was 5, but normalised to the starting population tested it was 12. About 10% of the initial population would have achieved the MTR outcome, similar to the result from studies of classic design. MTR had no imputation concerns. The majority (70% to 90%) of participants in all treatment groups experienced adverse events. Specific adverse events were more common with pregabalin than placebo, in particular dizziness, somnolence, weight gain, and peripheral oedema, with number needed to harm of 3.7, 7.4, 18, and 19 respectively for all doses combined (high quality evidence). Serious adverse events did not differ between active treatment groups and placebo (very low quality evidence). Withdrawals for any reason were more common with pregabalin than placebo only with the 600 mg dose in studies of classic design. Withdrawals due to adverse events were about 10% higher with pregabalin than placebo, but withdrawals due to lack of efficacy were about 6% lower (high quality evidence). Pregabalin 300 to 600 mg produces a major reduction in pain intensity over 12 to 26 weeks with tolerable adverse events for a small proportion of people (about 10% more than placebo) with moderate or severe pain due to fibromyalgia. The degree of pain relief is known to be accompanied by improvements in other symptoms, quality of life, and function. These results are similar to other effective medicines in fibromyalgia (milnacipran, duloxetine).",
        "gold": "We searched scientific databases for studies that looked at the effects of pregabalin in adults with fibromyalgia who had moderate or severe pain. The treatment had to last at least eight weeks. The evidence is current to March 2016. Eight studies satisfied the inclusion criteria, including three new studies for this update. Five studies randomised 3283 participants to immediate treatment with pregabalin or placebo. Two studies identified 687 out of 1492 participants who had a good pain response and could take the medicine, and then randomised them to continued treatment with pregabalin or placebo. Study quality was good. One other had no useful data. High quality evidence showed that 1 in 10 people with moderate or severe fibromyalgia pain reported a large fall in pain by a third to a half over 12 to 26 weeks. This is an outcome that people with fibromyalgia consider to be useful. The dose of pregabalin was 300 to 600 mg daily. Side effects occurred in 8 or 9 people in 10, often while adjusting to the medicine. Particular side effects were dizziness (affecting 1 in 4 participants), drowsiness (1 in 7), weight gain (1 in 18), and peripheral oedema (1 in 19) (high quality evidence). Serious side effects were no more common with pregabalin than with placebo, affecting 1 or 2 in 100. About 1 in 10 more participants taking pregabalin withdrew from the study because of side effects, and 1 in 17 fewer withdrew because the medicine was not working. The evidence was mostly of high quality, which means we are very confident that the true effect lies close to that of the estimate of the effect in this review. Concern about how information was handled when people left the studies was offset by other information showing that results were not impacted by this to any important degree."
    },
    {
        "index": "cochrane-simplification-test-64",
        "sentence": "We included one trial (involving 135 women with mild pre-eclampsia at term). An additional six studies are awaiting further assessment. The included trial compared magnesium sulphate with a placebo and was at a low risk of bias. The trial did not report any of this review's prespecified primary outcomes. There was no significant difference between magnesium sulphate and placebo in Apgar score less than seven at five minutes (risk ratio (RR) 0.51; 95% confidence interval (CI) 0.05 to 5.46; 135 infants), nor gestational age at birth (mean difference (MD) -0.20 weeks; 95% CI -0.62 to 0.22; 135 infants). There were significantly more maternal side effects (feeling warm and flushed) in the magnesium sulphate group than in the placebo group (RR 3.81; 95% CI 2.22 to 6.53; 135 women). However, no significant difference in adverse effects severe enough to cease treatment was observed (RR 3.04; 95% CI 0.13 to 73.42; 135 women). There were no significant differences seen between groups in the rates of postpartum haemorrhage (RR 4.06; 95% CI 0.47 to 35.38; 135 women) and caesarean section (RR 0.80; 95% CI 0.39 to 1.63; 135 women). There is currently insufficient evidence to assess the efficacy and safety of magnesium sulphate when administered to women for neuroprotection of the term fetus. As there has been recent evidence for the use of magnesium sulphate for neuroprotection of the preterm fetus, high-quality randomised controlled trials are needed to determine the safety profile and neurological outcomes for the term fetus. Strategies to reduce maternal side effects during treatment also require evaluation.",
        "gold": "This review included one randomised controlled study involving 135 women with mild pre-eclampsia (high blood pressure and/or protein in the urine). There was not enough evidence from this study to determine the effects of magnesium sulphate on babies born at term. Women receiving magnesium sulphate were more likely to feel warm and flushed in this study than women who received a placebo, but they were not more likely to stop treatment due to side effects. The rates of haemorrhage after birth and rates of caesarean birth were similar for women who received magnesium sulphate and those who received a placebo. More studies are needed to establish whether magnesium sulphate given to the mother at term is protective for the baby's brain. The babies in these trials should be followed up over a long period so that we can monitor the effects of magnesium on child development. We are awaiting further information from another six studies so that they can be assessed."
    },
    {
        "index": "cochrane-simplification-test-65",
        "sentence": "Four studies met all of the eligibility criteria for inclusion within the review. Two used combination therapies consisting of a pharmacotherapy combined with cognitive and behavioural therapies, whilst the remaining two used cognitive and behavioural therapy through counselling, one via text message support and the other delivered via clinic doctors trained in smoking cessation techniques. Smoking cessation data were pooled across all studies producing a statistically and clinically significant effect in favour of the intervention (risk ratio 1.43, 95%CI 1.03 to 1.98, p=0.032), however following sensitivity analysis a statistically non-significant but clinically significant effect was observed in favour of the intervention (risk ratio 1.33, 95%CI 0.95 to 1.85, p=NS) . A significant health disparity exists, whereby Indigenous populations, a minority, are over-represented in the burden of smoking-related morbidity and mortality. This review highlights the paucity of evidence available to evaluate the effectiveness of smoking cessation interventions, despite the known success of these interventions in non-Indigenous populations. Due to this lack of published investigations, the external validity of this review is limited, as is the ability to draw reliable conclusions from the results. The limited but available evidence reported does indicate that smoking cessation interventions specifically targeted at Indigenous populations can produce smoking abstinence. However this evidence base is not strong with a small number of methodologically sound trials investigating these interventions. More rigorous trials are now required to assist in bridging the gap between tobacco related health disparities in Indigenous and non-Indigenous populations.",
        "gold": "This review of four studies found that published studies evaluating smoking cessation interventions specifically aiming to reduce and/or stop the use of tobacco in Indigenous people are significantly lacking. The limited evidence reported in this review does indicate some benefit in these interventions to help Indigenous people stop smoking. However, the change in attitudes after one study was negative with fewer people 'ready to quit' after the smoking cessation intervention was completed. Consideration needs to be given to cultural differences and traditions when tailoring interventions for Indigenous people. Modified or innovative interventions and careful outcomes research are needed to improve the usefulness of smoking cessation interventions aimed at Indigenous populations."
    },
    {
        "index": "cochrane-simplification-test-66",
        "sentence": "We included 13 studies (5686 patients). We judged blinding of participants and personnel and blinding of outcome assessment to be at high risk in about 50% of the included studies and at low risk in 25% to 30% of the studies. Regardless of the high risk of performance bias these studies were included based on the low weight the studies had in the meta-analysis. We rated 75% of the studies as low risk for selection, attrition and reporting bias. All 13 studies reported some type of hospital mortality (28-day, 30-day, 60-day or ICU mortality). We considered studies of high-risk surgery patients (eight studies) and general intensive care patients (five studies) separately as subgroups for meta-analysis. The pooled risk ratio (RR) for mortality for the studies of general intensive care patients was 1.02 (95% confidence interval (CI) 0.96 to 1.09) and for the studies of high-risk surgery patients the RR was 0.98 (95% CI 0.74 to 1.29). Of the eight studies of high-risk surgery patients, five evaluated the effectiveness of pre-operative optimization but there was no difference in mortality when these studies were examined separately. PAC did not affect general ICU LOS (reported by four studies) or hospital LOS (reported by nine studies). Four studies, conducted in the United States (US), reported costs based on hospital charges billed, which on average were higher in the PAC groups. Two of these studies qualified for analysis and did not show a statistically significant hospital cost difference (mean difference USD 900, 95% CI -2620 to 4420, P = 0.62). PAC is a diagnostic and haemodynamic monitoring tool but not a therapeutic intervention. Our review concluded that use of a PAC did not alter the mortality, general ICU or hospital LOS, or cost for adult patients in intensive care. The quality of evidence was high for mortality and LOS but low for cost analysis. Efficacy studies are needed to determine if there are optimal PAC-guided management protocols, which when applied to specific patient groups in ICUs could result in benefits such as shock reversal, improved organ function and less vasopressor use. Newer, less-invasive haemodynamic monitoring tools need to be validated against PAC prior to clinical use in critically ill patients.",
        "gold": "We identified 13 studies comparing patients treated with and without the use of a PAC that studied a total of 5686 patients. These were studies of patients undergoing routine major surgery (eight) and studies of patients who were critically ill and admitted to ICUs (five). We analysed the studies for any trial related risks and performed appropriate statistical analysis to minimize any risk of bias or errors. The quality of evidence is high from this review and further research is very unlikely to change our confidence in the estimate of effect except for cost analysis. Our review found that there were no differences in the number of deaths during hospital stay, days spent in general ICUs, and days spent in hospital between patients who did and did not have a PAC inserted. Two US studies were analysed for hospital cost associated with or without a PAC and showed no difference in the cost. Neither group of patients studied showed any evidence of benefit or harm from using a PAC. The catheter is a monitoring tool that helps in diagnosis and is not a treatment modality. Insertion of PACs to help make treatment decisions in ICU patients should be individualized and should be done by experts in the field after adequate training in the interpretation of data. Studies need to be conducted to identify subgroups of ICU patients who can benefit, when the device is used in combination with standardized treatment plans, in reversing shock states and improving organ function."
    },
    {
        "index": "cochrane-simplification-test-67",
        "sentence": "Six studies (n = 478) of variable quality were included. A composite outcome of Infant Pain Scale (NIPS), Neonatal Facial Action Coding System (NFCS) and/or Premature Infant Pain Profile (PIPP) score was reported in 288 infants, who did not receive a sweet tasting solution. Meta-analysis showed a significant reduction in the venepuncture versus the heel lance group (SMD -0.76, 95% CI -1.00 to -0.52; I2 = 0%). When a sweet tasting solution was provided the SMD remained significant favouring the venepuncture group (SMD - 0.38, 95% CI -0.69 to -0.07). The typical RD for requiring more than one skin puncture for venepuncture versus heel lance (reported in 4 studies; n = 254) was -0.34 (95% CI -0.43 to -0.25; I2 = 97%). The NNT to avoid one repeat skin puncture was 3 (95% CI 2 to 4). Cry characteristics favoured the venepuncture group but the differences were reduced by the provision of sweet tasting solutions prior to either procedure. Venepuncture, when performed by a skilled phlebotomist, appears to be the method of choice for blood sampling in term neonates. The use of a sweet tasting solution further reduces the pain. Further well designed randomised controlled trials should be conducted in settings where several individuals perform the procedures.",
        "gold": "This review of trials found evidence that venepuncture, when done by a trained practitioner, caused less pain than heel lance. The use of a sweet tasting solution given to the baby prior to the event reduced pain further. The evidence included outcome measures using pain scales, how long the baby cried and how the mother rated their baby's pain."
    },
    {
        "index": "cochrane-simplification-test-68",
        "sentence": "Two small studies of poor methodological quality including 52 women with a dehisced and/or infected episiotomy wound at point of entry have been included. Only one small study presented data in relation to wound healing at less than four weeks, (the primary outcome measure for this review), although no reference was made to demonstrate how healing was measured. There was a trend to favour this outcome in the resuturing group, however, this difference was not statistically significant (risk ratio (RR) 1.69, 95% confidence interval (CI) 0.73 to 3.88, one study, 17 women). Similarly, only one trial reported on rates of dyspareunia (a secondary outcome measure for this review) at two months and six months with no statistically significant difference between both groups; two months, (RR 0.44, 95% CI 0.18 to 1.11, one study, 26 women) and six months, (RR 0.39, 95% CI 0.04 to 3.87, one study 32 women). This trial also included data on the numbers of women who resumed sexual intercourse by two months and six months. Significantly more women in the secondary suturing group had resumed intercourse by two months (RR 1.78, 95% CI 1.10 to 2.89, one study, 35 women), although by six months there was no significant difference between the two groups (RR 1.08, 95% CI, 0.91 to 1.28). Neither of the trials included data in relation to the following prespecified secondary outcome measures: pain at any time interval; the woman's satisfaction with the aesthetic results of the perineal wound; exclusive breastfeeding; maternal anxiety or depression. Based on this review, there is currently insufficient evidence available to either support or refute secondary suturing for the management of broken down perineal wounds following childbirth. There is an urgent need for a robust randomised controlled trial to evaluate fully the comparative effects of both treatment options.",
        "gold": "This review looked at randomised controlled trials of re-stitching broken down wounds compared with non-stitching. Two small studies were identified. One study, involving 17 women, showed a marginal tendency to improved healing in the women who were re-stitched, however, this evidence was not conclusive. In the other study involving 35 women, more women had resumed intercourse in the re-suturing group at two months. As the studies were small and of poor quality, it is not possible to draw conclusions about the best way to manage wound breakdown after childbirth. Therefore, there is an urgent need to conduct further studies to compare fully the benefits and risks of both treatments."
    },
    {
        "index": "cochrane-simplification-test-69",
        "sentence": "We included 18 studies involving 2521 participants. The methodological quality of 17 included studies was poor. Included RCTs separately compared medicinal herbs with different antiviral drugs, precluding any pooling of results. Only three indicated that compared with antiviral drugs, Chinese medicinal herbs may be effective in preventing influenza and alleviating influenza symptoms. 'Ganmao' capsules were found to be more effective than amantadine in decreasing influenza symptoms and speeding recovery in one study (in which adverse reactions were mentioned in the amantadine group although no data were reported). There were no significant differences between 'E Shu You' and ribavirin in treating influenza, nor in the occurrence of adverse reactions. Ten studies reported mild adverse reactions. Most Chinese medical herbs in the included studies showed similar effects to antiviral drugs in preventing or treating influenza. Few were shown to be superior to antiviral drugs. No obvious adverse events were reported in the included studies. However, current evidence remains weak due to methodological limitations of the trials. More high-quality RCTs with larger numbers of participants and clear reporting are needed.",
        "gold": "This updated review assessed the therapeutic effects and safety of Chinese medicinal herbs as an alternative and adjunctive therapy to other commonly used drugs for influenza. Eighteen studies involving 2521 participants were included in the review. 'Ganmao' capsules were found to be more effective than amantadine in decreasing influenza symptoms and aiding recovery in one study (in which adverse reactions were mentioned in the amantadine group although no data were reported). There were no significant differences between 'E Shu You' and ribavirin in treating influenza, nor in the occurrence of adverse reactions. The remaining 17 Chinese herbal trials showed a similar effect to antiviral drugs in preventing or treating influenza. However, since these included studies were of poor quality, the evidence does not support or reject the use of any Chinese herbal preparations for influenza. High-quality trials are required."
    },
    {
        "index": "cochrane-simplification-test-70",
        "sentence": "Our search strategy identified 8 studies (580 participants) as eligible for inclusion in this review. Interventions included: thrombolytic therapy versus placebo (1 study); low versus high dose thrombolytic therapy (1); alteplase versus urokinase (1); short versus long thrombolytic dwell (1); thrombolytic therapy versus percutaneous fibrin sheath stripping (1); fibrin sheath stripping versus over-the-wire catheter exchange (1); and over-the-wire catheter exchange versus exchange with and without angioplasty sheath disruption (1). No two studies compared the same interventions. Most studies had a high risk of bias due to poor study design, broad inclusion criteria, low patient numbers and industry involvement. Based on low certainty evidence, thrombolytic therapy may restore catheter function when compared to placebo (149 participants: RR 4.05, 95% CI 1.42 to 11.56) but there is no data available to suggest an optimal dose or administration method. The certainty of this evidence is reduced due to the fact that it is based on only a single study with wide confidence limits, high risk of bias and imprecision in the estimates of adverse events (149 participants: RR 2.03, 95% CI 0.38 to 10.73). Based on the available evidence, physical disruption of a fibrin sheath using interventional radiology techniques appears to be equally efficacious as the use of a pharmaceutical thrombolytic agent for the immediate management of dysfunctional catheters (57 participants: RR 0.92, 95% CI 0.80 to 1.07). Catheter patency is poor following use of thrombolytic agents with studies reporting median catheter survival rates of 14 to 42 days and was reported to improve significantly by fibrin sheath stripping or catheter exchange (37 participants: MD -27.70 days, 95% CI -51.00 to -4.40). Catheter exchange was reported to be superior to sheath disruption with respect to catheter survival (30 participants: MD 213.00 days, 95% CI 205.70 to 220.30). There is insufficient evidence to suggest any specific intervention is superior in terms of ensuring either dialysis adequacy or reduced risk of adverse events. Thrombolysis, fibrin sheath disruption and over-the-wire catheter exchange are effective and appropriate therapies for immediately restoring catheter patency in dysfunctional cuffed and tunnelled HD catheters. On current data there is no evidence to support physical intervention over the use of pharmaceutical agents in the acute setting. Pharmacological interventions appear to have a bridging role and long-term catheter survival may be improved by fibrin sheath disruption and is probably superior following catheter exchange. There is no evidence favouring any of these approaches with respect to dialysis adequacy or risk of adverse events. The current review is limited by the small number of available studies with limited numbers of patients enrolled. Most of the studies included in this review were judged to have a high risk of bias and were potentially influenced by pharmaceutical industry involvement. Further research is required to adequately address the question of the most efficacious and clinically appropriate technique for HD catheter dysfunction.",
        "gold": "We found eight studies involving 580 participants that tested the three different treatments. Studies also compared drug dosages and methods of administration. The quality of evidence is limited by small study size and high risk of bias. Thrombolytic therapy was probably better than placebo at restoring catheter function but there was no optimal dose or administration method. Physical disruption of a fibrin sheath may be equally effective as pharmaceutical thrombolytic agent for immediate management of catheter dysfunction. Catheter patency at two weeks is probably better following fibrin sheath stripping or catheter exchange compared to thrombolytic agent. Catheter exchange may be better than sheath disruption for long-term catheter survival and the use of both techniques together is probably best. There is currently insufficient evidence favouring any technique in terms of either dialysis adequacy or reduced risk of adverse events. Further research is required to adequately address the question of the most effective technique for haemodialysis catheter dysfunction."
    },
    {
        "index": "cochrane-simplification-test-71",
        "sentence": "We identified 17 trials reporting on 22 treatment comparisons (2674 patients randomised). Fifteen trials (20 treatment comparisons) reported results for tumour response and 11 trials (14 treatment comparisons) published time-to-event data for overall survival. There were 1532 deaths in 2116 women randomised to trials of the addition of a drug to the regimen and control (the regimen alone). There was no detectable difference in overall survival between these patients, with an overall HR of 0.96 (95% confidence interval (CI) 0.87 to 1.07, P = 0.47) and no significant heterogeneity. We found no difference in time to progression between these regimens, with an overall HR of 0.93 (95% CI 0.81 to 1.07, P = 0.31) and no significant heterogeneity. Addition of a drug to the regimen was favourably associated with overall tumour response rates (odds ratio 1.21, 95% CI 1.01 to 1.44, P = 0.04) although we observed significant heterogeneity for this outcome across the trials. Where measured, acute toxicities such as alopecia, nausea and vomiting and leucopenia were more common with the addition of a drug. The addition of one or more drugs to the regimen shows a statistically significant advantage for tumour response in women with metastatic breast cancer but the results suggest no difference in survival time or time to progression. The positive effect on tumour response was also associated with increased toxicity.",
        "gold": "This review investigated the value of adding one or more chemotherapy drugs to a chemotherapy regimen. We found that the addition of chemotherapy drug/s to a regimen caused greater shrinkage of the tumour seen with imaging but increased toxicity. There is insufficient evidence to determine if there is an impact on time to disease progression and overall survival."
    },
    {
        "index": "cochrane-simplification-test-72",
        "sentence": "Ten random or quasi-random controlled trials reported on a total of 1896 patients. There was no statistically significant effect on inpatient mortality (OR 1.10, 95% CI 0.56 to 2.16) or mortality to longest follow up (OR 0.92, 95% CI 0.65 to 1.29) but higher quality studies showed a larger non-significant increase in inpatient mortality (OR 1.52, 95% CI 0.86 to 2.68). Discharge to institutional care was reduced for the NLU (OR 0.44 95% CI 0.22 to 0.89) and functional status at discharge increased (SMD 0.37, 95% CI 0.20 to 0.54) but there was a near significant increase in inpatient stay (WMD 5.13 days 95% CI -0.5 days to 10.76 days). Early readmissions were reduced (OR 0.52 95% CI 0.34 to 0.80). One study compared a NLU for the chronically critically ill with ICU care. Mortality (OR 0.62 95% CI 0.35 to 1.10) and length of inpatient stay differ did not differ (WMD 2 days, 95% CI 10.96 to -6.96 days). Early readmissions were reduced (OR 0.33 95% CI 0.12 to 0.94). Costs of care on the NLU were higher for UK studies but lower for US based studies. There is some evidence that patients discharged from a NLU are better prepared for discharge but it is unclear if this is simply a product of an increased length of inpatient stay. No statistically significant adverse effects were noted but the possibility of increased early mortality cannot be discounted. More research is needed.",
        "gold": "Ten studies, including over 1800 patients, were analysed to determine if patients sent to a nursing led inpatient unit benefited or at least fared no worse than patients in a unit providing usual care. Compared to usual care, patients in nursing led inpatients units functioned better and experienced greater well-being; more patients were discharged home and not to an institution after about 3 months (but not after 6 months); fewer were readmitted back into hospital soon after discharge; but they stayed in hospital longer. The number of deaths during stay in hospital and 3 to 6 months after discharge was similar between the units (but there was a trend for more deaths early while in nursing led inpatients units that needs to be researched further). It is still not known whether nursing led inpatient units save money - studies in the United Kingdom found them more expensive than usual care units but studies in the United States found them cheaper."
    },
    {
        "index": "cochrane-simplification-test-73",
        "sentence": "We included 11 studies including 414 participants in the review. Two trials compared therapeutic ultrasound with placebo, two compared one ultrasound regimen with another, two compared ultrasound with another non-surgical intervention, and six compared ultrasound as part of a multi-component intervention with another non-surgical intervention (for example, exercises and splint). The risk of bias was low in some studies and unclear or high in other studies, with only two reporting that the allocation sequence was concealed and six reporting that participants were blinded. Overall, there is insufficient evidence that one therapeutic ultrasound regimen is more efficacious than another. Only two studies reported the primary outcome of interest, short-term overall improvement (any measure in which patients indicate the intensity of their complaints compared with baseline, for example, global rating of improvement, satisfaction with treatment, within three months post-treatment). One low quality trial with 68 participants found that when compared with placebo, therapeutic ultrasound may increase the chance of experiencing short-term overall improvement at the end of seven weeks treatment (RR 2.36; 95% CI 1.40 to 3.98), although losses to follow-up and failure to adjust for the correlation between wrists in participants with bilateral CTS in this study suggest that this data should be interpreted with caution. Another low quality trial with 60 participants found that at three months post-treatment therapeutic ultrasound plus splint increased the chance of short-term overall improvement (patient satisfaction) when compared with splint alone (RR 3.02; 95% CI 1.36 to 6.72), but decreased the chance of short-term overall improvement when compared with low-level laser therapy plus splint (RR 0.87; 95% CI 0.57 to 1.33), though participants were not blinded to treatment, it was unclear if the random allocation sequence was adequately concealed, and there was a potential unit of analysis error. Differences between groups receiving different frequencies and intensities of ultrasound, and between ultrasound as part of a multi-component intervention versus other non-surgical interventions, were generally small and not statistically significant for symptoms, function, and neurophysiologic parameters. No studies reported any adverse effects of therapeutic ultrasound, but this outcome was only measured in three studies. More adverse effects data are required before any firm conclusions on the safety of therapeutic ultrasound can be made. There is only poor quality evidence from very limited data to suggest that therapeutic ultrasound may be more effective than placebo for either short- or long-term symptom improvement in people with CTS. There is insufficient evidence to support the greater benefit of one type of therapeutic ultrasound regimen over another or to support the use of therapeutic ultrasound as a treatment with greater efficacy compared to other non-surgical interventions for CTS, such as splinting, exercises, and oral drugs. More methodologically rigorous studies are needed to determine the effectiveness and safety of therapeutic ultrasound for CTS.",
        "gold": "We searched for study reports and found 11 randomised controlled trials including 443 participants overall that assessed the safety and benefit of therapeutic ultrasound for people with carpal tunnel syndrome. The risk of bias of studies was low in some studies and unclear or high in others. There is only poor quality evidence from very limited data to suggest that therapeutic ultrasound may be more effective than placebo for either short- or long-term symptom improvement in people with carpal tunnel syndrome. There is insufficient evidence to support the greater benefit of one type of therapeutic ultrasound regimen over another or to support the use of therapeutic ultrasound as a treatment with greater efficacy compared with other non-surgical interventions for carpal tunnel syndrome, such as splinting, exercises, and oral drugs. Few studies measured adverse effects to therapeutic ultrasound. More research is needed to find out how effective and safe therapeutic ultrasound is for people with carpal tunnel syndrome, particularly in the long term."
    },
    {
        "index": "cochrane-simplification-test-74",
        "sentence": "We included eight studies involving approximately 10,000 participants. The active interventions were pravastatin, atorvastatin, simvastatin, clofibrate, and conjugated oestrogen. Fixed-effect analysis showed no overall effect on stroke recurrence but statin therapy alone had a marginal benefit in reducing subsequent cerebrovascular events in those with a previous history of stroke or TIA (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.77 to 1.00). There was no evidence that such intervention reduced all-cause mortality or sudden death (OR 1.00, 95% CI 0.83 to 1.20). Three statin trials showed a reduction in subsequent serious vascular events (OR 0.74, 95% CI 0.67 to 0.82). There is evidence that statin therapy in patients with a history of ischaemic stroke or TIA significantly reduces subsequent major coronary events but only marginally reduces the risk of stroke recurrence. There is no clear evidence of beneficial effect from statins in those with previous haemorrhagic stroke and it is unclear whether statins should be started immediately post stroke or later. In view of this and the evidence of the benefit of statin therapy in those with a history of CHD, patients with ischaemic stroke or TIA, with or without a history of established CHD, should receive statins.",
        "gold": "Studies have shown that interventions for reducing either total serum cholesterol or low density lipoprotein cholesterol levels reduce the risk of coronary heart disease (CHD) and stroke events in people with a history of CHD. However, for stroke patients the relation between the level of serum cholesterol and cholesterol subfractions with the risk of future stroke or cardiovascular events is unclear. This review, which includes eight studies involving approximately 10,000 participants, shows statin therapy, but not other lipid-lowering measures, reduces the risk of subsequent major vascular events and a marginal benefit in decreasing stroke events, but not all-cause mortality in those with a history of ischaemic cerebrovascular disease."
    },
    {
        "index": "cochrane-simplification-test-75",
        "sentence": "Eleven campaigns met the inclusion criteria for this review. Studies differed in design, settings, duration, content and intensity of intervention, length of follow-up, methods of evaluation and also in definitions and measures of smoking behaviour used. Among seven campaigns reporting smoking prevalence, significant decreases were observed in the California and Massachusetts statewide tobacco control campaigns compared with the rest of the USA. Some positive effects on prevalence in the whole population or in the subgroups were observed in three of the remaining seven studies. Three large-scale campaigns of the seven presenting results for tobacco consumption found statistically significant decreases. Among the eight studies presenting abstinence or quit rates, four showed some positive effect, although in one of them the effect was measured for quitting and cutting down combined. Among the three that did not show significant decreases, one demonstrated a significant intervention effect on smokers and ex-smokers combined. There is evidence that comprehensive tobacco control programmes which include mass media campaigns can be effective in changing smoking behaviour in adults, but the evidence comes from a heterogeneous group of studies of variable methodological quality. One state-wide tobacco control programme (Massachusetts) showed positive results up to eight years after the campaign. Another (California) showed positive results during the period of adequate funding and implementation and in final evaluation since the beginning of the programme. Six of nine studies carried out in communities or regions showed some positive effects on smoking behaviour and at least one significant change in smoking prevalence (Sydney). The intensity and duration of mass media campaigns may influence effectiveness, but length of follow-up and concurrent secular trends and events can make this difficult to quantify. No consistent relationship was observed between campaign effectiveness and age, education, ethnicity or gender.",
        "gold": "We searched up until 30th November 2016, and found 11 relevant studies for this review. The numbers of participants varied between the included studies. All of the studies involved adults, although some studies also included younger people (14+ or 15+). Campaigns involved TV, radio, print media and billboard advertising. Studies differed in setting, duration, content of the intervention, length of observation, measures of smoking behaviour and the way of showing results. Two campaigns reported definite decreases in smoking prevalence, and some positive effects were observed in another three. Three large-scale campaigns reported lower tobacco consumption. Three studies showed some positive effect in abstinence or quit rates. One study did not show significant decreases but did demonstrate an effect of the intervention on smokers and ex-smokers combined. Tobacco control programmes that include mass media campaigns may change smoking behaviour in adults, but the evidence comes from studies of variable quality and scale and often occur in an environment where there are other influences on smoking, making it hard to isolate the effects of the media campaign itself. No consistent patterns by age, education, ethnicity or gender were found. There were problems with the design and conduct of all of the studies, which clouded the evidence. It would help if future studies could include comparator communities where there are no mass media interventions taking place to get a better estimate of the effect of the mass media campaign."
    },
    {
        "index": "cochrane-simplification-test-76",
        "sentence": "We included 24 studies with a total of 2166 participants, 23 of which provided data for meta-analysis. Thirteen studies had low risk of selection bias, five studies reported adequate blinding of outcome assessment and 15 studies had low risk of attrition bias. Seventeen studies that compared yoga versus no therapy provided moderate-quality evidence showing that yoga improved health-related quality of life (pooled SMD 0.22, 95% CI 0.04 to 0.40; 10 studies, 675 participants), reduced fatigue (pooled SMD -0.48, 95% CI -0.75 to -0.20; 11 studies, 883 participants) and reduced sleep disturbances in the short term (pooled SMD -0.25, 95% CI -0.40 to -0.09; six studies, 657 participants). The funnel plot for health-related quality of life was asymmetrical, favouring no therapy, and the funnel plot for fatigue was roughly symmetrical. This hints at overall low risk of publication bias. Yoga did not appear to reduce depression (pooled SMD -0.13, 95% CI -0.31 to 0.05; seven studies, 496 participants; low-quality evidence) or anxiety (pooled SMD -0.53, 95% CI -1.10 to 0.04; six studies, 346 participants; very low-quality evidence) in the short term and had no medium-term effects on health-related quality of life (pooled SMD 0.10, 95% CI -0.23 to 0.42; two studies, 146 participants; low-quality evidence) or fatigue (pooled SMD -0.04, 95% CI -0.36 to 0.29; two studies, 146 participants; low-quality evidence). Investigators reported no serious adverse events. Four studies that compared yoga versus psychosocial/educational interventions provided moderate-quality evidence indicating that yoga can reduce depression (pooled SMD -2.29, 95% CI -3.97 to -0.61; four studies, 226 participants), anxiety (pooled SMD -2.21, 95% CI -3.90 to -0.52; three studies, 195 participants) and fatigue (pooled SMD -0.90, 95% CI -1.31 to -0.50; two studies, 106 participants) in the short term. Very low-quality evidence showed no short-term effects on health-related quality of life (pooled SMD 0.81, 95% CI -0.50 to 2.12; two studies, 153 participants) or sleep disturbances (pooled SMD -0.21, 95% CI -0.76 to 0.34; two studies, 119 participants). No trial adequately reported safety-related data. Three studies that compared yoga versus exercise presented very low-quality evidence showing no short-term effects on health-related quality of life (pooled SMD -0.04, 95% CI -0.30 to 0.23; three studies, 233 participants) or fatigue (pooled SMD -0.21, 95% CI -0.66 to 0.25; three studies, 233 participants); no trial provided safety-related data. Moderate-quality evidence supports the recommendation of yoga as a supportive intervention for improving health-related quality of life and reducing fatigue and sleep disturbances when compared with no therapy, as well as for reducing depression, anxiety and fatigue, when compared with psychosocial/educational interventions. Very low-quality evidence suggests that yoga might be as effective as other exercise interventions and might be used as an alternative to other exercise programmes.",
        "gold": "We found 24 studies that involved 2166 women. Our evidence is current to January 2016. We found that women in 11 studies had completed surgery, chemotherapy and radiotherapy; women in three studies were currently undergoing chemotherapy; and women in five studies were currently undergoing radiotherapy. Women in the remaining five studies were either undergoing treatment or were not. Studies used a variety of questionnaires to assess quality of life, depression, fatigue and/or sleep disturbances. We found that yoga was more effective than no therapy in improving quality of life and reducing fatigue and sleep disturbances. We also found that yoga was better for reducing depression, anxiety and fatigue in women when compared with psychosocial or educational interventions such as counselling. We are fairly certain that these observed results are probably true. Yoga might be as effective as exercise in improving quality of life and reducing fatigue; we do not have enough data to be sure. Studies have poorly reported risks of yoga. However, we found no evidence of serious risks of yoga among women with a diagnosis of breast cancer. No studies have assessed effects of yoga in women given a diagnosis of breast cancer more than five years ago. Our findings indicate that women with a diagnosis of breast cancer can use yoga as supportive therapy for improving their quality of life and mental health, in addition to standard cancer treatments."
    },
    {
        "index": "cochrane-simplification-test-77",
        "sentence": "We included one retrospective, single-institution study that compared post-operative imaging within 48 hours (early post-operative imaging) with no early post-operative imaging among 125 people who had surgery for glioblastoma (GBM: World Health Organization (WHO) grade 4 glioma). Most patients in the study underwent maximal surgical resection followed by combined radiotherapy and temozolomide treatment. Although patient characteristics in the study arms were comparable, the study was at high risk of bias overall. Evidence from this study suggested little or no difference between early and no early post-operative imaging with respect to overall survival (deaths) at one year after diagnosis of GBM (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.61 to 1.21; 48% vs 55% died, respectively; very low certainty evidence) and little or no difference in overall survival (deaths) at two years after diagnosis of GBM (RR 1.06, 95% CI 0.91 to 1.25; 86% vs 81% died, respectively; very low certainty evidence). No other review outcomes were reported. We found no evidence on the effectiveness of other imaging schedules. In addition, we identified no relevant economic evaluations assessing the efficiency of the different imaging strategies. The effect of different imaging strategies on survival and other health outcomes remains largely unknown. Existing imaging schedules in glioma seem to be pragmatic rather than evidence-based. The limited evidence suggesting that early post-operative brain imaging among GBM patients who will receive combined chemoradiation treatment may make little or no difference to survival needs to be further researched, particularly as early post-operative imaging also serves as a quality control measure that may lead to early re-operation if residual tumour is identified. Mathematical modelling of a large glioma patient database could help to distinguish the optimal timing of surveillance imaging for different types of glioma, with stratification of patients facilitated by assessment of individual tumour growth rates, molecular biomarkers and other prognostic factors. In addition, paediatric glioma study designs could be used to inform future research of imaging strategies among adults with glioma.",
        "gold": "We looked for studies involving adults with gliomas that compared current practice of doing scans at specific time points with other approaches. We found only one study meeting our criteria. This was from a cancer centre in the USA, looking at glioblastoma patients (those with the most aggressive gliomas) who had been treated between 2006 and 2016. The study involved 125 people and split them into those scanned within two days of surgery (early scan) with those who were not. They showed that doing the early scan made no change to the chance of being alive at one and two years after diagnosis. This might have been because the early scans were not used to change treatments, which mainly were to receive standard radiotherapy and temozolomide, and we could not tell if the patients' surgeon(s) were different or had different approaches to care. We judged this suggestion of little change in survival time with or without early scanning to be very uncertain. The number of people included over 10 years was small, and the decision whether or not to have a scan after surgery was based on surgeon's choice. It was not clear whether the surgeon(s) involved or their approaches to care differed, nor whether a person's care might have been changed in light of early imaging. The other search did not find any studies looking at the value of different imaging approaches. We still do not know whether doing scans regularly at specific times after glioma diagnosis changes how well patients do. The limited evidence, suggesting early scans after operations do not affect survival, is unreliable and more research is needed, especially as early scans may also help surgeons improve their practice, and decide whether to repeat the operation earlier than they might otherwise have chosen to do. The best timings and reasons for scanning brain gliomas in adults are not known. Lessons might be learned from studies involving children, and by looking at large collections of clinical trials. It is also important to study the potential costs and benefits of different strategies."
    },
    {
        "index": "cochrane-simplification-test-78",
        "sentence": "We included three studies randomising 161 people with schizophrenia. Data were available for only two of our seven prestated main outcomes. Clinically important improvement in global state was measured using the Clinical Global Impression (CGI). There was no clear difference between chlorpromazine and metiapine groups (2 RCTs, n = 120, RR 1.11, 95% CI 0.84 to 1.47, very low quality evidence) and numbers of participants with parkinsonism at eight weeks were similar (2 RCTs, n = 70, RR 0.97, 95% CI 0.46 to 2.03, very low quality evidence). There were no useable data available for the other key outcomes of clinically important improvement in mental state, readmission due to relapse, satisfaction with treatment, aggressive or violent behaviour, or cost of care. Chlorpromazine has been the mainstay treatment for schizophrenia for decades, yet available evidence comparing this drug to metiapine fails to provide high-quality trial based data. However, the need to determine whether metiapine is more or less effective than chlorpromazine seems to be lacking in clinical relevance and future research on this comparison seems unlikely.",
        "gold": "In November 2015, the Information Specialist of the Cochrane Schizophrenia group searched their specialised register for relevant clinical trials. The search identified four reports. We inspected these reports and found they referred to three trials, randomising people with schizophrenia to receive chlorpromazine or metiapine. Main results Our review now includes three studies with 161 participants. The studies revealed no real differences between chlorpromazine and metiapine for improvement in global state or incidence of parkinsonism (an umbrella term for symptoms such as tremor (shaking), bradykinesia (slow movement), rigidity (stiffness), and postural instability (difficulty in balancing). No data were reported for our other main areas of interest: mental state, service use, satisfaction with treatment, behaviour or cost of care. Conclusions We cannot draw firm conclusions from the data provided. The number of studies and number of participants in each study is small, all studies are also short term. Therefore, we rated the reported evidence as very low quality. However, metiapine is not a highly prescribed or used antipsychotic medicine, so although our evidence is poor, it probably will remain the best available evidence as it is unlikely new trials comparing metiapine with chlorpromazine will be conducted in the future."
    },
    {
        "index": "cochrane-simplification-test-79",
        "sentence": "Twenty-three studies were identified for inclusion. Probiotics were not superior to placebo for any outcome measured. The use of nitroimidazole antibiotics appeared to reduce the risk of clinical (RR 0.23; 95%CI 0.09 to 0.57, NNT=4) and endoscopic (RR 0.44; 95%CI 0.26 to 0.74, NNT = 4) recurrence relative to placebo. However, these agents were associated with higher risk of serious adverse events (RR 2.39, 95% CI 1.5 to 3.7). Mesalamine therapy was associated with a significantly reduced risk of clinical recurrence (RR 0.76; 95% CI 0.62 to 0.94, NNT = 12), and severe endoscopic recurrence (RR 0.50; 95% CI 0.29 to 0.84, NNT = 8) when compared to placebo. Azathioprine/6MP was also associated with a significantly reduced risk of clinical recurrence (RR 0.59; 95% CI 0.38 to 0.92, NNT = 7), and severe endoscopic recurrence (RR 0.64; 95% CI 0.44 to 0.92, NNT = 4), when compared to placebo. Neither agent had a higher risk than placebo of serious adverse events. When compared to azathioprine/6MP, mesalamine was associated with a higher risk of any endoscopic recurrence (RR 1.45, 95% CI 1.03 to 2.06), but a lower risk of serious adverse events (RR 0.51; 95% CI 0.30 to 0.89). There was no significant difference between mesalamine and azathioprine/6MP for any other outcome. There are insufficient randomised controlled trials of infliximab, budesonide, tenovil and interleukin-10 to draw conclusions. Nitro-imidazole antibiotics, mesalamine and immunosuppressive therapy with azathioprine/6-MP or infliximab all appear to be superior to placebo for the prevention of post-operative recurrence of Crohn's disease. The cost, toxicity and tolerability of these approaches require careful consideration to determine the optimal approach for post-operative prophylaxis.",
        "gold": "This review examines the results of published studies which have looked at the effect of using medication following surgery for Crohn's disease as a mean of preventing the return (recurrence) of inflammation. Where possible, the results of studies were combined to compare the results of different treatments. A number of medications appeared to reduce the recurrence of inflammation, including metronidazole, mesalamine, azathioprine, 6-mercaptopurine and infliximab. Given that some of these medications have significant side-effects, the decision to use them requires a careful balancing of the risks and benefits for each individual patient"
    },
    {
        "index": "cochrane-simplification-test-80",
        "sentence": "We included seven trials (825 participants). We judged the majority of the trials to have a high or unclear risk of bias. The psychosocial interventions considered in the studies were: cognitive-behavioural coping skills training (one study), twelve-step programme (one study), brief intervention (three studies), motivational interviewing (two studies), and brief motivational interviewing (one study). Two studies were considered in two comparisons. There were no data for the secondary outcome, alcohol-related harm. The results were as follows. Comparison 1: cognitive-behavioural coping skills training versus twelve-step programme (one study, 41 participants) There was no significant difference between groups for either of the primary outcomes (alcohol abstinence assessed with Substance Abuse Calendar and breathalyser at one year: risk ratio (RR) 2.38 (95% confidence interval [CI] 0.10 to 55.06); and retention in treatment, measured at end of treatment: RR 0.89 (95% CI 0.62 to 1.29), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was very low. Comparison 2: brief intervention versus treatment as usual (three studies, 197 participants) There was no significant difference between groups for either of the primary outcomes (alcohol use, measured as scores on the Alcohol Use Disorders Identification Test (AUDIT) or Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) at three months: standardised mean difference (SMD) 0.07 (95% CI -0.24 to 0.37); and retention in treatment, measured at three months: RR 0.94 (95% CI 0.78 to 1.13), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was low. Comparison 3: motivational interviewing versus treatment as usual or educational intervention only (three studies, 462 participants) There was no significant difference between groups for either of the primary outcomes (alcohol use, measured as scores on the AUDIT or ASSIST at three months: SMD 0.04 (95% CI -0.29 to 0.37); and retention in treatment, measured at three months: RR 0.93 (95% CI 0.60 to 1.43), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was low. Comparison 4: brief motivational intervention (BMI) versus assessment only (one study, 187 participants) More people reduced alcohol use (by seven or more days in the past month, measured at six months) in the BMI group than in the control group (RR 1.67; 95% CI 1.08 to 2.60). There was no difference between groups for the other primary outcome, retention in treatment, measured at end of treatment: RR 0.98 (95% CI 0.94 to 1.02), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was moderate. Comparison 5: motivational interviewing (intensive) versus motivational interviewing (one study, 163 participants) There was no significant difference between groups for either of the primary outcomes (alcohol use, measured using the Addiction Severity Index-alcohol score (ASI) at two months: MD 0.03 (95% CI 0.02 to 0.08); and retention in treatment, measured at end of treatment: RR 17.63 (95% CI 1.03 to 300.48), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was low. We found low to very low-quality evidence to suggest that there is no difference in effectiveness between different types of psychosocial interventions to reduce alcohol consumption among people who use illicit drugs, and that brief interventions are not superior to assessment-only or to treatment as usual. No firm conclusions can be made because of the paucity of the data and the low quality of the retrieved studies.",
        "gold": "We found seven studies that examined five talking therapies among 825 people with drug problems. Cognitive-behavioural coping skills training (CBCST) is a talking therapy that focuses on changing the way people think and act. The twelve-step programme is based on theories from Alcoholics Anonymous and aims to motivate the person to develop a desire to stop using drugs or alcohol. Motivational interviewing (MI) helps people to explore and resolve doubts about changing their behaviour. It can be delivered in group, individual and intensive formats. Brief motivational interviewing (BMI) is a shorter MI that takes 45 minutes to three hours. Brief interventions are based on MI but they take only five to 30 minutes and are often delivered by a non-specialist. Six of the studies were funded by the National Institutes for Health or by the Health Research Board; one study did not report its funding source. We found that the talking therapies led to no differences, or only small differences, for the outcomes assessed. These included abstinence, reduced drinking, and substance use. One study found that there may be no difference between CBCST and the twelve-step programme. Three studies found that there may be no difference between brief intervention and usual treatment. Three studies found that there may be no difference between MI and usual treatment or education only. One study found that BMI is probably better at reducing alcohol use than usual treatment (needle exchange), but found no differences in other outcomes. One study found that intensive MI may be somewhat better than standard MI at reducing severity of alcohol use disorder among women, but not among men and found no differences in other outcomes. It remains uncertain whether talking therapies reduce alcohol and drug use in people who also have problems with other drugs. High-quality studies are missing and are needed. The quality of the evidence was moderate for brief and intensive motivational interviewing, but low for brief interventions and standard motivational interviewing, and very low for CBCST versus twelve-step programme."
    },
    {
        "index": "cochrane-simplification-test-81",
        "sentence": "We identified 23 trials with a total of 1586 participants. Fifty-eight per cent of these participants were from five unpublished studies. Quinine was compared to placebo (20 trials, n = 1140), vitamin E (four trials, n = 543), a quinine-vitamin E combination (three trials, n = 510), a quinine-theophylline combination (one trial, n = 77), and xylocaine injections into the gastrocnemius muscle (one trial, n = 24). The most commonly used quinine dosage was 300 mg/day (range 200 to 500 mg). We found no new trials for inclusion when searches were updated in 2014. The risk of bias in the trials varied considerably. All 23 trials claimed to be randomised, but only a minority described randomisation and allocation concealment adequately. Compared to placebo, quinine significantly reduced cramp number over two weeks by 28%, cramp intensity by 10%, and cramp days by 20%. Cramp duration was not significantly affected. A significantly greater number of people suffered minor adverse events on quinine than placebo (risk difference (RD) 3%, 95% confidence interval (CI) 0% to 6%), mainly gastrointestinal symptoms. Overdoses of quinine have been reported elsewhere to cause potentially fatal adverse effects, but in the included trials there was no significant difference in major adverse events compared with placebo (RD 0%, 95% CI -1% to 2%). One participant suffered from thrombocytopenia (0.12% risk) on quinine. A quinine-vitamin E combination, vitamin E alone, and xylocaine injections into gastrocnemius were not significantly different to quinine across all outcomes, including adverse effects. Based on a single trial comparison, quinine alone was significantly less effective than a quinine-theophylline combination but with no significant differences in adverse events. There is low quality evidence that quinine (200 mg to 500 mg daily) significantly reduces cramp number and cramp days and moderate quality evidence that quinine reduces cramp intensity. There is moderate quality evidence that with use up to 60 days, the incidence of serious adverse events is not significantly greater than for placebo in the identified trials, but because serious adverse events can be rarely fatal, in some countries prescription of quinine is severely restricted. Evidence from single trials suggests that theophylline combined with quinine improves cramps more than quinine alone, and the effects of xylocaine injections into gastrocnemius are not significantly different to quinine across all outcomes. Low or moderate quality evidence shows no significant difference between quinine and vitamin E or quinine and quinine-vitamin E mixture. Further research into these alternatives, as well other pharmacological and non-pharmacological treatments, is thus warranted. There is no evidence to judge optimal dosage or duration of quinine treatment. Further studies using different dosages and measurement of serum quinine levels will allow a therapeutic range to be defined for muscle cramp. Because serious adverse events are not common, large population studies are required to more accurately inform incidence. Longer lengths of follow-up in future trials will help determine the duration of action following cessation of quinine as well as long-term adverse events. The search for new therapies, pharmacological and nonpharmacological, should continue and further trials should compare vitamin E, quinine-vitamin E combination, and quinine-theophylline mixture with quinine.",
        "gold": "This review includes 23 trials, with 1586 participants. The trials compared quinine or quinine-based medicines against inactive treatment (placebo) or other active treatments. We found no new studies when we searched the medical literature again and updated the review in 2014. The risk of bias in the included trials varied considerably. All 23 trials claimed to be randomised, but many failed to clearly describe how participants were assigned to treatments. There is low quality evidence that quinine (200 mg to 500 mg daily) significantly reduces cramp number and cramp days and moderate quality evidence that quinine reduces cramp intensity. There is moderate quality evidence that there are more minor adverse events with quinine compared to placebo but no increase in major adverse events. However, there are reliable reports from other sources that an overdose of quinine can cause serious harm including death. Low or moderate quality evidence shows there is no significant difference when comparing quinine to vitamin E or to a quinine-vitamin E mixture. There is evidence from one trial that theophylline combined with quinine improves cramps more than quinine alone. In a single trial there was no significant difference when comparing quinine to xylocaine injections. More research is needed to clarify the best dose and duration of treatment, as well as alternatives to quinine for cramps. The evidence is current to October 2014."
    },
    {
        "index": "cochrane-simplification-test-82",
        "sentence": "We identified seven trials (five parallel, two cross-over) enrolling a total of 406 individuals amongst whom 118 cross-over participants additionally served as their own controls. Three trials enrolled women with pregnancy-associated leg cramps (N = 202) and four trials enrolled idiopathic cramp sufferers (N = 322 including cross-over controls). Magnesium was compared to placebo in six trials and to no treatment in one trial. For idiopathic cramps (largely older adults presumed to have nocturnal leg cramps), differences in measures of cramp frequency, magnesium versus placebo, were small, not statistically significant, and without heterogeneity (I2 = 0%). This includes the primary endpoint, percentage change from baseline in the number of cramps per week at four weeks (-3.93%, 95% confidence interval (CI) -21.12% to 13.26%, moderate quality evidence) and the difference in the number of cramps per week at four weeks (0.01 cramps/week, 95% CI -0.52 to 0.55, moderate quality evidence). The percentage of individuals experiencing a 25% or better reduction in cramp rate from baseline was also no different, being 8% lower in the magnesium group (95% CI -28% to 12%, moderate quality evidence). Similarly, no statistically significant difference was found at four weeks in measures of cramp intensity (moderate quality evidence) or cramp duration (low quality evidence). Meta-analysis was not possible for trials of pregnancy-associated leg cramps. The single study comparing magnesium to no treatment failed to find statistically significant benefit on a three-point ordinal scale of overall treatment efficacy. The two trials comparing magnesium to placebo differed in that one trial found no benefit on frequency or intensity measures while the other found benefit for both. Withdrawals due to adverse events were not significantly different than placebo. While we could not determine the number of subjects with minor adverse events, studies of oral magnesium generally described potential side effects as similar in frequency to placebo. It is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults experiencing skeletal muscle cramps. In contrast, for those experiencing pregnancy-associated rest cramps the literature is conflicting and further research in this patient population is needed. We found no randomized controlled trials evaluating magnesium for exercise-associated muscle cramps or disease state-associated muscle cramps (for example amyotrophic lateral sclerosis/motor neuron disease).",
        "gold": "We searched for all high quality published studies evaluating the effectiveness of magnesium to prevent muscle cramps and found four studies in older adults and three studies in pregnant women. There were no studies of people who cramp while exercising and no studies on people who cramp because of underlying medical problems. The four studies in older adults (a total of 322 participants including controls in cross-over studies) collectively suggest that magnesium is unlikely to provide a meaningful benefit in reducing the frequency or severity of cramps in that population. We consider this evidence to be of moderate quality. In contrast, the three studies in pregnant women (202 participants) are collectively inconclusive since one study found benefit in reducing both cramp frequency and cramp pain while the other two found no benefit. More research on magnesium in pregnant women is needed; however, older adult cramp sufferers appear unlikely to benefit from this therapy. While we could not determine the rate of unwanted side effects, the study withdrawal rates and adverse event discussions suggest the treatment is well tolerated."
    },
    {
        "index": "cochrane-simplification-test-83",
        "sentence": "We included one RCT that studied the effects of a six-month, home-based, combined muscle strength and recumbent cycle ergometry training program versus usual care in 14 ambulatory people with SMA. The age range of the participants was between 10 years and 48 years. The study was evaluator-blinded, but personnel and participants could not be blinded to the intervention, which placed the results at a high risk of bias. Participants performed strength training as prescribed, but 50% of the participants did not achieve the intended aerobic exercise training regimen. The trial used change in walking distance on the six-minute walk test as a measure of function; a minimal detectable change is 24.0 m. The change from baseline to six months' follow-up in the training group (9.4 m) was not detectably different from the change in the usual care group (-0.14 m) (mean difference (MD) 9.54 m, 95% confidence interval (CI) -83.04 to 102.12; N = 12). Cardiopulmonary exercise capacity, assessed by the change from baseline to six months' follow-up in peak oxygen uptake (VO2max) was similar in the training group (-0.12 mL/kg/min) and the usual care group (-1.34 mL/kg/min) (MD 1.22 mL/kg/min, 95% CI -2.16 to 4.6; N = 12). A clinically meaningful increase in VO2max is 3.5 mL/kg/min. The trial assessed function on the Hammersmith Functional Motor Scale - Expanded (HFMSE), which has a range of possible scores from 0 to 66, with an increase of 3 or more points indicating clinically meaningful improvement. The HFMSE score in the training group increased by 2 points from baseline to six months' follow-up, with no change in the usual care group (MD 2.00, 95% CI -2.06 to 6.06; N = 12). The training group showed a slight improvement in muscle strength, expressed as the manual muscle testing (MMT) total score, which ranges from 28 (weakest) to 280 (strongest). The change from baseline in MMT total score was 6.8 in the training group compared to -5.14 in the usual care group (MD 11.94, 95% CI -3.44 to 27.32; N = 12). The trial stated that training had no statistically significant effects on fatigue and quality of life. The certainty of evidence for all outcomes was very low because of study limitations and imprecision. The study did not assess the effects of physical exercise training on physical activity levels. No study-related serious adverse events or adverse events leading to withdrawal occurred, but we cannot draw wider conclusions from this very low-certainty evidence. It is uncertain whether combined strength and aerobic exercise training is beneficial or harmful in people with SMA type 3, as the quality of evidence is very low. We need well-designed and adequately powered studies using protocols that meet international standards for the development of training interventions, in order to improve our understanding of the exercise response in people with SMA type 3 and eventually develop exercise guidelines for this condition.",
        "gold": "We included one trial that studied the effects of a six-month, home-based training program that combined exercises to increase muscle strength with aerobic exercise training (exercise that increases breathing and heart rate). The aerobic exercise training used in the trial was recumbent cycling training (seated cycling, with back support). The study included 14 people with SMA type 3, all of whom were able to walk. The participants were between 10 years and 48 years old and had SMA type 3 of mild-to-moderate severity. The nature of the intervention made it impossible to hide the treatment group from participants or personnel, which is an important limitation when measurements rely on participant assessments or effort. The included study was supported by the United States Department of Defense and the SMA Foundation. Participants performed strength training as prescribed, but only half of them completed the full aerobic exercise program. The effects of physical exercise training in people with SMA type 3 remain unclear, as the evidence is very uncertain."
    },
    {
        "index": "cochrane-simplification-test-84",
        "sentence": "Two trials (N = 149) were included. In both trials, allocation concealment was inadequate and arrangements for blinding of outcome assessment were unclear. One trial (81 patients with cervical radiculopathy) found that surgical decompression was superior to\u00a0physiotherapy or cervical collar immobilization in the short-term for pain, weakness or sensory loss; at one year, there were no significant differences between groups. One trial (68 patients with mild functional deficit associated with cervical myelopathy) found\u00a0no significant differences between surgery and conservative treatment in three years following treatment. A substantial proportion of cases were lost to follow-up. Both small trials had significant risks of bias and do not provide reliable evidence on the effects of surgery for cervical spondylotic radiculopathy or myelopathy. It is unclear whether the short-term risks of surgery are offset by long-term benefits. Further research is very likely to have an impact on the estimate of effect and our confidence in it. There is low quality evidence that surgery may provide pain relief faster than physiotherapy or hard collar immobilization in patients with cervical radiculopathy; but there is little or no difference in the long-term. There is very low quality evidence that patients with mild myelopathy feel subjectively better shortly after surgery, but there is little or no difference in the long-term.",
        "gold": "This review of two trials with 149 patients found no conclusive evidence to support surgical treatment for people with degeneration, radiculopathy or myelopathy. Possible limitations of this review include the the lack of large trials and the risk of bias associated with these studies. Further research is very likely to change the estimate of effects and our confidence in the results. Future large-scale randomised trials with better methods are needed to provide clear evidence on the balance between risk and benefit from surgery for individuals with cervical degeneration with radiculopathy or myelopathy."
    },
    {
        "index": "cochrane-simplification-test-85",
        "sentence": "Nine studies met our inclusion criteria, five RCTs, one CCT and three ITSs. Six studies compared telephone consultation versus normal care; four by a doctor, one by a nurse and one by a clinic clerk. Three studies compared telephone consultation by different types of health care workers; two compared nurses with doctors and one compared health assistants with doctors or nurses. Three of five studies found a decrease in visits to GP's but two found a significant increase in return consultations. In general at least 50% of calls were handled by telephone advice alone. Seven studies looked at accident and emergency department visits, six showed no difference between the groups and one, of nurse telephone consultation, found an increase in visits. Two studies reported deaths and found no difference between nurse telephone triage and normal care. Telephone consultation appears to reduce the number of surgery contacts and out-of-hours visits by general practitioners. However, questions remain about its affect on service use and further rigorous evaluation is needed with emphasis on service use, safety, cost and patient satisfaction.",
        "gold": "Nine studies were found and analysed to determine whether telephone consultation was safe and effective. In general, at least half of the calls were handled by telephone only (without the need for face-to-face visits). It was found that telephone consultation appears to decrease the number of immediate visits to doctors and does not appear to increase visits to emergency departments. It is still unclear though, whether it is just delaying visits to a later time. Telephone consultation also appears to be safe and people were just as satisfied using the telephone as going to see someone face-to-face. There are still questions about its effectiveness and more research into the use, cost, safety and satisfaction of telephone consultation is needed."
    },
    {
        "index": "cochrane-simplification-test-86",
        "sentence": "We included a total of 84 trials (22,872 participants), with 70/84 studies reporting interventions in higher risk individuals or settings. Studies with follow-up periods of at least four months were of more interest in assessing the sustainability of intervention effects and were also less susceptible to short-term reporting or publication bias. Overall, the risk of bias assessment showed that these studies provided moderate or low quality evidence. At four or more months follow-up, we found effects in favour of MI for the quantity of alcohol consumed (standardised mean difference (SMD) \u22120.11, 95% confidence interval (CI) \u22120.15 to \u22120.06 or a reduction from 13.7 drinks/week to 12.5 drinks/week; moderate quality evidence); frequency of alcohol consumption (SMD \u22120.14, 95% CI \u22120.21 to \u22120.07 or a reduction in the number of days/week alcohol was consumed from 2.74 days to 2.52 days; moderate quality evidence); and peak blood alcohol concentration, or BAC (SMD \u22120.12, 95% CI \u22120.20 to 0.05, or a reduction from 0.144% to 0.131%; moderate quality evidence). We found a marginal effect in favour of MI for alcohol problems (SMD \u22120.08, 95% CI \u22120.17 to 0.00 or a reduction in an alcohol problems scale score from 8.91 to 8.18; low quality evidence) and no effects for binge drinking (SMD \u22120.04, 95% CI \u22120.09 to 0.02, moderate quality evidence) or for average BAC (SMD \u22120.05, 95% CI \u22120.18 to 0.08; moderate quality evidence). We also considered other alcohol-related behavioural outcomes, and at four or more months follow-up, we found no effects on drink-driving (SMD \u22120.13, 95% CI \u22120.36 to 0.10; moderate quality of evidence) or other alcohol-related risky behaviour (SMD \u22120.15, 95% CI \u22120.31 to 0.01; moderate quality evidence). Further analyses showed that there was no clear relationship between the duration of the MI intervention (in minutes) and effect size. Subgroup analyses revealed no clear subgroup effects for longer-term outcomes (four or more months) for assessment only versus alternative intervention controls; for university/college vs other settings; or for higher risk vs all/low risk participants. None of the studies reported harms related to MI. The results of this review indicate that there are no substantive, meaningful benefits of MI interventions for preventing alcohol use, misuse or alcohol-related problems. Although we found some statistically significant effects, the effect sizes were too small, given the measurement scales used in the included studies, to be of relevance to policy or practice. Moreover, the statistically significant effects are not consistent for all misuse measures, and the quality of evidence is not strong, implying that any effects could be inflated by risk of bias.",
        "gold": "We found a total of 84 randomised controlled trials (studies where participants were randomly divided into one of two or more treatment or control groups) that compared MI with either no intervention or with a different approach. Seventy of these trials focused on higher risk individuals or settings. We were mainly interested in trials with a follow-up period of 4 or more months, and the typical follow-up period was 12 months. We also evaluated the quality of the studies' designs and their applicability to our research, finding that these studies provided moderate to low quality evidence. In 66 trials, the MI consisted of a single, individual session. In 12 studies, young people attended multiple individual sessions or mixtures of both individual sessions and group sessions. Six trials used group MI sessions only. The length of MI sessions varied, but in 57 studies it was one hour or less. The shortest MI intervention was 10 to 15 minutes, and the longest had five dedicated MI sessions over a 19-hour period. Settings for the trials varied: 58 of the 84 studies took place in college (mainly university but also four vocational) settings. The remaining trials took place in healthcare locations, a youth centre, local companies, a job-related training centre, an army recruitment setting, UK drug agencies and youth prisons. The total number of young adults was 22,872, aged on average from 15 to 24 years old. The proportion of males in the trials with both males and females ranged from 22% to 90%. The ethnicity of the young adults was typically mixed, but 52 of the 67 studies that reported ethnicity involved mostly white people. At four or more months follow-up, we found only small or borderline effects showing that MI reduced the quantity of alcohol consumed, frequency of alcohol consumption, alcohol problems and peak blood alcohol concentration (BAC). We didn't find any effects for binge drinking, average BAC, drink-driving or other alcohol-related risky behaviour. We found no relationship between the length of MI and its effectiveness. Also, there were no clear subgroup differences in effects when we examined the type of comparison group (assessment only control or alternative intervention, the setting (college/university vs other settings), or risk status (higher risk students vs all/low-risk students). None of the studies reported harms related to MI. Although we found some significant effects for MI, our reading of these results is that the strength of the effects was slight and therefore unlikely to confer any advantage in practice. Overall, there is only low or moderate quality evidence for the effects found in this review. Many of the studies did not adequately describe how young people were allocated to the study groups or how they concealed the group allocation to participants and personnel. Study drop-outs were also an issue in many studies. These problems with study quality could result in inflated estimates of MI effects, so we cannot rule out the possibility that any slight effects observed in this review are overstated. The US National Institutes of Health provided funding for half (42/84) of the studies included in this review. Twenty-nine studies provided no information about funding, and only eight papers had a clear conflict of interest statement."
    },
    {
        "index": "cochrane-simplification-test-87",
        "sentence": "This review includes 29 parallel randomised controlled trials (RCTs) (n = 2210), although not all reported relevant or useable data. All participants had asthma, and follow-up ranged from 2 to 26 weeks. Most studies were at low or unclear risk of selection and attrition biases and at high risk for biases associated with blinding. We considered most of the evidence to be of low quality owing to these biases and to imprecision in the estimates of effect. We classified studies into three comparisons: enhanced face-to-face training session(s), multi-media-delivered inhaler training (e.g. DVD, computer app or game) and technique feedback devices. Differences between interventions, populations and outcome measures limited quantitative analyses, particularly for exacerbations, adverse events, unscheduled visits to a healthcare provider and absenteeism from work or school. Enhanced inhaler technique education and multi-media training improved technique in most studies immediately after the intervention and at follow-up, although the variety of checklists used meant that this was difficult to assess reliably. For both adults and children, how and when inhaler technique was assessed appeared to affect whether inhaler technique improved and by how much. Analyses of the numbers of people who demonstrated correct or 'good enough' technique were generally more useful than checklist scores. Adult studies of enhanced education showed benefit when this metric was used at 2 to 26 weeks' follow-up (odds ratio (OR) 5.00, 95% confidence interval (CI) 1.83 to 13.65; 258 participants; three studies; 31 per 100 with correct technique in the control group compared with 69 (95% CI 45 to 86) in the education group; moderate-quality evidence). A similar result was seen in studies looking at feedback devices at four weeks' follow-up (OR 4.80, 95% CI 1.87 to 12.33; 97 participants; one study; 51 per 100 with correct technique in the control group compared with 83 (95% CI 66 to 93) in the feedback group; low-quality evidence). However, the benefit of multi-media training for adults even immediately after the intervention was uncertain (OR 2.15, 95% CI 0.84 to 5.50; 164 participants; two studies; I\u00b2 = 49%; 30 per 100 in the control group with correct technique compared with 47 (95% CI 26 to 70) in the multi-media group; moderate-quality evidence). Evidence tended to be less clear for children, usually because results were based on fewer and smaller studies. Some studies did not report exacerbations in a way that allowed meta-analysis; others provided inconclusive results. Inhaler technique interventions provided some benefit for asthma control and quality of life but generally did not lead to consistent or important clinical benefits for adults or children. Confidence intervals included no difference or did not reach a threshold that could be considered clinically important. Responder analyses sometimes showed improvement among more people in the intervention groups, even though the mean difference between groups was small. We found no evidence about harms. Although interventions to improve inhaler technique may work in some circumstances, the variety of interventions and measurement methods used hampered our ability to perform meta-analyses and led to low to moderate confidence in our findings. Most included studies did not report important improvement in clinical outcomes. Guidelines consistently recommend that clinicians check regularly the inhaler technique of their patients; what is not clear is how clinicians can most effectively intervene if they find a patient's technique to be inadequate, and whether such interventions will have a discernible impact on clinical outcomes.",
        "gold": "We found 29 studies involving 2210 people with asthma. Studies lasted between 2 and 26 weeks. Studies reported inhaler technique on a range of different checklists. We grouped studies into three types: studies testing enhanced face-to-face training session(s), studies using multi-media to deliver inhaler training (e.g. a video, computer app or game) and studies testing devices that give people visual or audio feedback about technique. Studies tested different types of training and used different measures to gauge success, meaning that we could not bring data together. This was particularly true when we tried to assess effects on asthma attacks, adverse events, visits to a healthcare provider and absences from work or school. Both face-to-face and multi-media inhaler training improved inhaler technique in most studies, although results varied depending on how and when each technique was assessed. Some studies reported the number of people who had correct or 'good enough' technique. More people had correct or 'good enough' technique after face-to-face training and with feedback devices. But the benefit of multi-media training for adults was uncertain. Interventions that provide inhaler training may bring some benefit for quality of life and asthma control among adults and children, but results were varied and studies were small. Children may receive some benefit but results tended to be less clear for children because fewer and smaller studies have included children as participants. For studies like these, it is not possible to blind people to their assigned group. This may bias how people behave or respond to questionnaires, which reduced our confidence in the findings. We were uncertain about other results because studies did not provide enough data to show clear benefit. We cannot say for sure what is the best way to help people learn how to use their inhaler properly. It is important that patients understand how their inhaler works, so they should ask their doctor or nurse for help. We also use Cochrane Reviews to make suggestions for future research. We suggest that trials should last longer than six months and should report adherence information. The most useful information reported was the number of people who had 'good enough' inhaler technique, so we urge future trials to report this as well."
    },
    {
        "index": "cochrane-simplification-test-88",
        "sentence": "Three small trials, involving 226 participants, were included. One trial included patients with presumed ischaemic stroke without computerised tomography (CT) verification, and the other two trials included patients with CT-verified ICH. Data on the primary outcome measure (death and dependency) were not available in any of the trials. Death and disability could be calculated in the larger ICH trial without differences between the mannitol and control groups. Case fatality was not reported in the trial of ischaemic stroke. Case fatality did not differ between the mannitol and control groups in the ICH trials. Adverse events were either not found or not reported. The change in clinical condition was reported in two trials, and the proportion of those with worsening or not improving condition did not differ significantly between mannitol-treated patients and controls. Based on these three trials neither beneficial nor harmful effects of mannitol could be proved. Although no statistically significant differences were found between the mannitol-treated and control groups, the confidence intervals for the treatment effect estimates were wide and included both clinically significant benefits and clinically significant harms as possibilities. There is currently not enough evidence to support the routine use of mannitol in acute stroke patients. Further trials are needed to confirm or refute whether mannitol is beneficial in acute stroke.",
        "gold": "This review of three small trials, involving 226 participants, found that there was not enough evidence to decide if mannitol improves survival or prevents disability after stroke. The treatment can cause a number of adverse effects, but no serious adverse events were reported in the trials included in this review. More research is needed."
    },
    {
        "index": "cochrane-simplification-test-89",
        "sentence": "Six trials were identified, with 425 patients randomized to D-penicillamine and 258 to placebo. A statistically significant benefit was observed for D-penicillamine when compared to placebo for all three-dose ranges and for most outcome measures including: tender joint counts, pain, physician's global assessments and ESR. The standardized weighted mean differences between treatment and placebo in moderate doses were -0.51 [95% CI -0.88, -0.14] for tender joint counts, -0.56 (95% CI -0.87, -0.26) for pain and -0.97 (95% CI -1.25, -0.70) for global assessment. The difference for ESR was -10.6 mm/hr. Similar results were observed for the higher dose group. Total withdrawals were significantly higher in the moderate and high dosage D-penicillamine groups (OR=1.63 and 2.13 respectively), mostly due to increased adverse reactions (OR = 2.60 and 4.95 respectively), including renal and hematological abnormalities. D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.",
        "gold": "Penicillamine is a penicillin derived compound. Studies showed that this could be used to treat rheumatoid arthritis originally in 1950. It was frequently used in the past, but its use has declined with the increasing use of other disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate. The purpose of this summary was to find out if penicillamine is helpful in the treatment of rheumatoid arthritis. Penicillamine was seen to be beneficial for all ranges of dosages for disease activity on tender joint pain, physician global assessment and sed rate. No major differences were observed between placebo and low dose penicillamine (<500 mg/day). For higher dosages, patients on penicillamine were twice as likely to withdraw than those receiving placebo 500 to <1000 mg/day. D-penicillamine appears be have a clinical and statistical benefit on the disease activity of patients with rheumatoid arthritis. Its benefit is similar to that of other such drugs, such as disease modifying anti-rheumatic drugs (DMARDs). More adverse reactions are seen in patients being treated with D-penicillamine."
    },
    {
        "index": "cochrane-simplification-test-90",
        "sentence": "We included four relevant trials. All of them were of low quality. All of studies used a decoction containing Huangqi compounds as the intervention with chemotherapy. The intervention groups of three studies were compared to a chemotherapy alone control group, the fourth study compared the decoction of Huangqi compounds with two other Chinese herbal interventions. None of the studies reported on primary outcome using Common Toxicity Criteria (CTC). There was a significant reduction in the proportion of patients who experienced nausea & vomiting when decoctions of Huangqi compounds were given in addition to chemotherapy. There was also a decrease in the rate of leucopenia (WBC <3 x 10^9 per L). Huangqi compounds were also associated with increases in the proportions of T-lymphocyte subsets: CD3; CD4 and CD8. Huangqi decoctions had no significant effects on Immunoglobulins G, A or M. Despite the included studies being of low quality, the results suggest that decoctions of Huangqi compounds may stimulate immunocompetent cells and decrease side effects in patients treated with chemotherapy. Due to the methodological limitations of the studies, there is no robust demonstration of benefit. We found no evidence of harm arising from the use of Chinese herbs. We need high quality randomised controlled studies investigating the effects of decoctions of Chinese herbs, particularly Astragalus spp.(as in Huangqi), upon chemotherapy-related side effects.",
        "gold": "We have performed a systematic review of the potential benefits of Chinese herbal medicines in patients being treated with chemotherapy for colorectal cancer. We identified four relevant studies, which included a total of 342 patients, with adequately reported data. We conclude that, from the limited information available, there is some evidence of benefit from decoctions of Huangqi compounds. Compared with patients treated by chemotherapy alone, patients treated with chemotherapy and Huangqi decoctions were less likely to experience nausea and vomiting or low white cell counts. There was some evidence to suggest that the decoctions also stimulated cells of the immune system, but did not affect the levels of antibodies in the blood. We could find no evidence of harm arising from the use of Huangqi decoctions. Our results suggest that further, larger-scale, trials of the use of Huangqi decoctions in the prevention of chemotherapy-related side-effects are needed."
    },
    {
        "index": "cochrane-simplification-test-91",
        "sentence": "We reviewed 394 titles and abstracts and nine ClinicalTrials.gov records and included three RCTs that met our eligibility criteria. The three trials included a total of 866 participants aged four to 55 years with RP of all forms of genetic predisposition. One trial evaluated the effect of vitamin A alone, one trial evaluated DHA alone, and a third trial evaluated DHA and vitamin A versus vitamin A alone. None of the RCTs had protocols available, so selective reporting bias was unclear for all. In addition, one trial did not specify the method for random sequence generation, so there was an unclear risk of bias. All three trials were graded as low risk of bias for all other domains. We did not perform meta-analysis due to clinical heterogeneity of participants and interventions across the included trials. The primary outcome, mean change of visual field from baseline at one year, was not reported in any of the studies. No toxicity or adverse events were reported in these three trials. No trial reported a statistically significant benefit of vitamin supplementation on the progression of visual field loss or visual acuity loss. Two of the three trials reported statistically significant differences in ERG amplitudes among some subgroups of participants, but these results have not been replicated or substantiated by findings in any of the other trials. Based on the results of three RCTs, there is no clear evidence for benefit of treatment with vitamin A and/or DHA for people with RP, in terms of the mean change in visual field and ERG amplitudes at one year and the mean change in visual acuity at five years follow-up. In future RCTs, since some of the studies in this review included unplanned subgroup analysis that suggested differential effects based on previous vitamin A exposure, investigators should consider examining this issue. Future trials should take into account the changes observed in ERG amplitudes and other outcome measures from trials included in this review, in addition to previous cohort studies, when calculating sample sizes to assure adequate power to detect clinically and statistically meaningful difference between treatment arms.",
        "gold": "We identified three clinical studies conducted in the USA and Canada. These studies included 866 participants with RP aged between four and 55 years, who were followed for an average of four years after administration of treatment. One study compared a fish oil extract (docosahexaenoic acid (DHA, 400 mg per day)), to placebo (pretend medicine); the second study compared vitamin A (15000 IU per day) to vitamin E (400 IU per day) and to very low levels of vitamins (vitamin A trace + vitamin E trace); and the third study compared DHA (1200 mg per day) + vitamin A (15000 IU per day) to vitamin A alone (15000 IU per day). The evidence is current to August 2013. All these studies measured the following outcomes: worsening in visual field, worsening in visual acuity (sharpness), and worsening in electroretinography results. Generally, comparison of participants who received vitamin A with or without fish oils (DHA) with participants who received placebo, did not show any difference for these outcomes, which means that the use of high-dose vitamin A or fish oils does not significantly slow progressive visual loss in people with RP. None of the studies reported any systemic adverse events from vitamin A or fish oil. However, the long-term adverse effects of high-dose vitamin A and fish oil are not known. The trials appear to have been well designed and well conducted, so we determined the quality was good for all included studies."
    },
    {
        "index": "cochrane-simplification-test-92",
        "sentence": "We included three RCTs with a total of 414 participants at risk of job loss. The majority of participants had IA, most with RA and to a lesser degree AS. The interventions aimed to prevent job loss and improve work functioning in several ways: firstly by evaluating work changes or adaptations and secondly by providing any person-directed interventions including vocational counselling, advice or education. Interventions directly targeted at the work environment were minimal and included workplace visits (one trial) or any actions by an occupational physician (one trial). The duration or dose of the interventions varied from two 1.5-hour sessions (one RCT) over five months, two consultation and multidisciplinary treatments during three months (one RCT), to six to eight individual or group sessions over six months (also one RCT). All participants were recruited through rheumatology clinics, both in or outside hospitals. Included trials investigated job loss (n = two RCTs; 382 participants), work absenteeism and work functioning (n = one RCT; 32 participants). Overall, we evaluated the two smaller trials as having a high risk of bias and the large trial as having a low risk of bias. Trials showed marked differences in how they performed on risk of bias items, particularly on performance bias. We assessed the quality of the evidence using the GRADE approach and judged there to be very low quality evidence across the three reported outcomes. Of the two RCTs investigating job loss, the larger one (n = 242 participants) reported a large statistically significant reduction in job loss (relative risk (RR) = 0.35, 95% confidence interval (CI) 0.18 to 0.68) and the other RCT (n = 140) reported similar effects in both groups, although the CI was very wide (RR = 1.05, 95% CI 0.53 to 2.06). The latter one probably suffered from performance bias and we judged it to have a high risk of bias. The one small trial investigating sickness absenteeism found uncertain results at six months' follow-up (MD = -2.42 days, 95% CI -5.03 to 0.19). Finally, in the same small trial investigating work functioning using the Rheumatoid Arthritis-Work Instability Scale (RA-WIS), there was a moderate improvement of intermediate term work functioning (six months; scale range 0 to 23; mean improvement -4.67 points, 95% CI -8.43 to -0.91). We identified no adverse effects in the publications of the three trials. This Cochrane review of three RCTs found very low quality evidence overall for job loss prevention interventions having an effect on job loss, work absenteeism and work functioning in workers with inflammatory arthritis. While this review highlights that further high quality RCTs are required, the results suggest that these strategies have potential to be effective.",
        "gold": "We searched the available literature up to 30 April 2014. We included three randomised controlled trials with 414 participants who had IA and who were at risk of losing their jobs. These trials first evaluated how the work environment could be adapted and then provided counselling, advice or education for work problems. One trial gave two 1.5-hour sessions over five months. Another trial gave two consultation and multidisciplinary treatments during three months. The third trial gave six to eight individual or group sessions over six months. The included trials compared the effects of interventions to usual care (two trials) or to written information only (one trial). Two of the included trials measured the effect of the intervention on job loss (382 participants) when the third measured effect on work absenteeism and work functioning (32 participants). When considered together, the evidence from the three trials was of very low quality. Two trials found different results on job loss measured at two years' follow-up: one trial on job counselling found a large reduction in people who lost their job and the other trial found similar effects in both groups. Another trial did not find a considerable effect on absenteeism at six months' follow-up but found a moderate improvement in work functioning. Because of positive results from one RCT with long term follow-up, we see potential for job loss prevention interventions in helping workers with inflammatory arthritis to stay at work. The certainty of these results is limited by the very low quality evidence of the three RCTs overall."
    },
    {
        "index": "cochrane-simplification-test-93",
        "sentence": "We identified three eligible studies that included a total of 285 neonates (140 received arginine) from three countries. We assessed the overall methodological quality of the included studies as good. We noted a statistically significant reduction in risk of development of NEC (any stage) among preterm neonates in the arginine group compared with the placebo group (RR 0.38, 95% confidence interval (CI) 0.23 to 0.64; I2 = 27%) (RD -0.19, 95% CI -0.28 to -0.10; I2 = 0%) and rated the quality of evidence as moderate. The number needed to treat for an additional beneficial outcome (NNTB) as required to prevent the development of NEC (any stage) was 6 (95% CI 4 to 10). Study results showed a statistically significant reduction in risk of development of NEC stage 1 (RR 0.37, 95% CI 0.15 to 0.90; I2 = 52%) (RD -0.07, 95% CI -0.14 to -0.01; I2 = 0%) and NEC stage 3 (RR 0.13, 95% CI 0.02 to 1.03; I2 = 0%) (RD -0.05, 95% CI -0.09 to -0.01; I2 = 89%) in the arginine group compared with the control group; the quality of evidence was moderate. Arginine supplementation was associated with a significant reduction in death related to NEC (RR 0.18, 95% CI 0.03 to 1.00; I2 = 0%) (RD -0.05, 95% CI -0.09 to -0.01; I2 = 87%). Results showed clinical heterogeneity in mortality rates. Mortality due to any cause was not significantly different between arginine and control or no treatment groups (RR 0.77, 95% CI 0.41 to 1.45; I2 = 42%) (RD -0.03, 95% CI -0.10 to 0.04; I2 = 79%). Investigators noted no significant side effects directly attributable to arginine, including hypotension or alterations in glucose homeostasis. Follow-up data from one trial revealed no statistically significant differences in adverse outcomes (cerebral palsy, cognitive delay, bilateral blindness or hearing loss requiring hearing aids) at 36 months. Limitations of the present findings include a relatively small overall sample size. Administration of arginine to preterm infants may prevent development of NEC. Because information was provided by three small trials that included 285 participants, the data are insufficient at present to support a practice recommendation. A multi-centre randomised controlled study that is focused on the incidence of NEC, particularly at more severe stages (2 and 3), is needed.",
        "gold": "Review authors searched the literature for controlled studies evaluating the efficacy and safety of arginine supplementation. Adding extra arginine to a preterm infant's feed reduced the risk of NEC in three good quality studies that included 285 infants born at less than 34 weeks' gestation. Six infants had to be treated, for one to benefit from treatment. Researchers reported no significant side effects directly attributable to too much arginine in the first 28 days, and one study reported no long-term (36 months) developmental delays. Possible effects of supplementing arginine include lower blood pressure and changes in blood glucose control. Arginine supplementation may reduce the incidence and severity of NEC in preterm infants. Results are limited, as studies included only a few patients. A large study that includes infants from multiple centres is needed to verify these findings."
    },
    {
        "index": "cochrane-simplification-test-94",
        "sentence": "No new trials were found for inclusion in this update. Four studies involving 1943 participants with acute sinusitis met our inclusion criteria. The trials were well-designed and double-blind and studied INCS versus placebo or no intervention for 15 or 21 days. The rates of loss to follow-up were 7%, 11%, 41% and 10%. When we combined the results from the three trials included in the meta-analysis, participants receiving INCS were more likely to experience resolution or improvement in symptoms than those receiving placebo (73% versus 66.4%; risk ratio (RR) 1.11; 95% confidence interval (CI) 1.04 to 1.18). Higher doses of INCS had a stronger effect on improvement of symptoms or complete relief: for mometasone furoate 400 \u00b5g versus 200 \u00b5g (RR 1.10; 95% CI 1.02 to 1.18 versus RR 1.04; 95% CI 0.98 to 1.11). No significant adverse events were reported and there was no significant difference in the drop-out and recurrence rates for the two treatment groups and for groups receiving higher doses of INCS. Current evidence is limited for acute sinusitis confirmed by radiology or nasal endoscopy but supports the use of INCS as a monotherapy or as an adjuvant therapy to antibiotics. Clinicians should weigh the modest but clinically important benefits against possible minor adverse events when prescribing therapy.",
        "gold": "A critical systematic review of the literature found four well-conducted, randomised, placebo-controlled intervention studies, involving 1943 participants treated for 15 or 21 days. The results suggest that there may be a modest effect with INCS in the resolution or improvement of symptoms. Only minor adverse events such as epistaxis, headache and nasal itching were reported. Given the small number of studies included in this review, it is recommended that further randomised controlled trials be conducted. The evidence is up to date as of May 2013."
    },
    {
        "index": "cochrane-simplification-test-95",
        "sentence": "The administration of prophylactic vancomycin reduced the incidence of both total neonatal nosocomial sepsis and coagulase negative staphylococcal sepsis in eligible preterm infants. Mortality, length of stay, and evidence of vancomycin toxicity were not significantly different between the two groups. There was insufficient evidence to ascertain the risks of development of vancomycin resistant organisms in the nurseries involved in these trials. The use of prophylactic vancomycin in low doses reduces the incidence of nosocomial sepsis in the neonate. The methodologies of these studies may have contributed to the low rate of sepsis in the treated groups, as the blood cultures drawn from central lines may have failed to grow due to the low levels of vancomycin in the infusate. Although there is a theoretical concern regarding the development of resistant organisms with the administration of prophylactic antibiotic, there is insufficient evidence to ascertain the risks of development of vancomycin resistant organisms. Few clinically important benefits have been demonstrated for very low birth weight infants treated with prophylactic vancomycin. It therefore appears that routine prophylaxis with vancomycin should not be undertaken at present.",
        "gold": "The review of trials found that low dose continuous infusions, or low dose intermittent administration, of vancomycin reduce the risk of a baby getting sepsis in the neonatal intensive care unit. There is not enough evidence to show if this approach increases antibiotic resistance in nurseries."
    },
    {
        "index": "cochrane-simplification-test-96",
        "sentence": "Fourteen reports of 13 RCTs on dressings or topical agents for postoperative wounds healing by secondary intention were identified. WOUND HEALING: Whilst a single small trial of aloe vera supplementation vs gauze suggests delayed healing with aloe vera, the results of this trial are un interpretable since there was a large differential loss to follow up. A plaster cast applied to an amputation stump accelerated wound healing compared with elastic compression, WMD -25.60 days, 95% CI -49.08 to -2.12 days (1 trial). There were no statistically significant differences in healing for other dressing comparisons (e.g. gauze, foam, alginate; 11 trials).  PAIN: Gauze was associated with significantly more pain for patients than other dressings (4 trials).  PATIENT SATISFACTION: Patients treated with gauze were less satisfied compared with those receiving alternative dressings (3 trials).  COSTS: Gauze is inexpensive but its use is associated with the use of significantly more nursing time than foam (2 trials).  LENGTH OF HOSPITAL STAY: Four trials showed no difference in length of hospital stay. One trial found shorter hospital stay in people after amputation when plaster casts were applied compared with elastic compression (WMD -30.10 days; 95% CI -49.82 to -10.38). We found only small, poor quality trials; the evidence is therefore insufficient to determine whether the choice of dressing or topical agent affects the healing of surgical wounds healing by secondary intention. Foam is best studied as an alternative for gauze and appears to be preferable as to pain reduction, patient satisfaction and nursing time.",
        "gold": "There are many kinds of dressings and topical agents available but few have been evaluated in trials. This review did not find any evidence that any one dressing or topical agent speeds up the healing of surgical wounds healing by secondary intention more than another, although gauze may be associated with greater pain or discomfort for the patient."
    },
    {
        "index": "cochrane-simplification-test-97",
        "sentence": "In 2014, we added seven trials for a new total of 11. Five reports were published before 1985 and six from 2005 to 2014. They included 1482 women. Four trials examined combined oral contraceptives (COCs), and three studied a levonorgestrel-releasing intrauterine system (LNG-IUS). We found two trials of progestin-only pills (POPs) and two of the etonogestrel-releasing implant. Older studies often lacked quantified results. Most trials did not report significant differences between the study arms in breastfeeding duration, breast milk composition, or infant growth. Exceptions were seen mainly in older studies with limited information. For breastfeeding duration, two of eight trials indicated a negative effect on lactation. A COC study reported a negative effect on lactation duration compared to placebo but did not quantify results. Another trial showed a lower percentage of the LNG-IUS group breastfeeding at 75 days versus the nonhormonal IUD group (reported P < 0.05) but no significant difference at one year. For breast milk volume, two older studies indicated lower volume for the COC group versus the placebo group. One trial did not quantify results. The other showed lower means (mL) for the COC group, e.g. at 16 weeks (MD -24.00, 95% CI -34.53 to -13.47) and at 24 weeks (MD -24.90, 95% CI -36.01 to -13.79). Another four trials did not report any significant difference between the study groups in milk volume or composition with two POPs, a COC, or the etonogestrel implant. Seven trials studied infant growth; one showed greater weight gain (grams) for the etonogestrel implant versus no method for six weeks (MD 426.00, 95% CI 58.94 to 793.06) but less compared with depot medroxyprogesterone acetate (DMPA) from 6 to 12 weeks (MD -271.00, 95% CI -355.10 to -186.90). The others studied POPs, COCs versus POPs, or an LNG-IUS. Results were not consistent across the 11 trials. The evidence was limited for any particular hormonal method. The quality of evidence was moderate overall and low for three of four placebo-controlled trials of COCs or POPs. The sensitivity analysis included six trials with moderate quality evidence and sufficient outcome data. Five trials indicated no significant difference between groups in breastfeeding duration (etonogestrel implant insertion times, COC versus POP, and LNG-IUS). For breast milk volume or composition, a COC study showed a negative effect, while an implant trial showed no significant difference. Of four trials that assessed infant growth, three indicated no significant difference between groups. One showed greater weight gain in the etonogestrel implant group versus no method but less versus DMPA.",
        "gold": "We included 11 studies with a total of 1482 women. These trials looked at many methods: pills, an implant, the injectable 'Depo,' and a hormonal intrauterine device (IUD). Some older reports did not have much data. Most trials showed no major difference due to hormonal birth control use. Two of eight trials noted less breastfeeding among women using hormonal birth control. One was a combined pill with few results and the other a hormonal IUD. In one study, the implant group infants gained more weight than those in the no-method group but less weight than infants in the 'Depo' group. Two trials noted that a combined pill had a negative effect on breast milk volume or content. One report did not have much data. The other showed lower volume for combined pill users than for women taking pills with only progestin. We found little information on any specific birth control method, with usually two studies per method. Results were not consistent across all trials. The data were of moderate quality overall. The results of better quality showed little effect on breastfeeding or infant growth."
    },
    {
        "index": "cochrane-simplification-test-98",
        "sentence": "No randomised controlled trials were identified but 10 controlled before-after studies from Australia, Singapore and the USA met our inclusion criteria. We grouped them according to the extent to which they adjusted for regression to the mean (RTM) and spillover effects. Total casualty crashes: the only study that adjusted for both reported a rate ratio of 0.71 (95% CI to 0.55, 0.93); for three that partially adjusted for RTM but failed to consider spillover, rate ratio was 0.87 (95% CI to 0.77, 0.98); one that made no adjustments had a rate ratio of 0.80 (95% CI 0.58 to 1.12). Right-angle casualty crashes: rate ratio for two studies that partially addressed RTM was 0.76 (95% CI 0.54 to 1.07). Total crashes: the study addressing both RTM and spillover reported a rate ratio of 0.93 (95% CI 0.83 to 1.05); one study that partially addressed RTM had a rate ratio of 0.92 (95% CI 0.73 to 1.15); the pooled rate ratio from the five studies with no adjustments was 0.74 (95% CI 0.53 to 1.03). Red-light violations: one study found a rate ratio of 0.53 (95% CI 0.17 to 1.66). Red-light cameras are effective in reducing total casualty crashes. The evidence is less conclusive on total collisions, specific casualty collision types and violations, where reductions achieved could be explained by the play of chance. Most evaluations did not adjust for RTM or spillover, affecting their accuracy. Larger and better controlled studies are needed.",
        "gold": "This review looked for studies of their effectiveness in reducing the number of times that drivers drive through red lights and the number of crashes. Very little research has been done and much of it has not allowed for the statistical problems that occur when recording this kind of information. However, five studies in Australia, Singapore and the USA all found that use of red-light cameras cut the number of crashes in which there were injuries. In the best conducted of these studies, the reduction was nearly 30%. More research is needed to determine best practice for red-light camera programmes, including how camera sites are selected, signing policies, publicity programmes and penalties."
    },
    {
        "index": "cochrane-simplification-test-99",
        "sentence": "Four trials involving 494 participants were included. Three studies involving 383 participants provided data on the proportion of participants who had achieved a therapeutic INR by day five. Significant benefit of a 10-mg warfarin nomogram was observed (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.05 to 1.54; moderate quality evidence), although with substantial heterogeneity (I2 = 90%). The review authors analyzed each study separately because it was not possible to perform a subgroup analysis by inpatient or outpatient status. One study showed significant benefit of a 10-mg warfarin nomogram for the proportion of outpatients with VTE who had achieved a therapeutic INR by day five (RR 1.78, 95% CI 1.41 to 2.25), with the number needed to treat for an additional beneficial outcome (NNTB = 3, 95% CI 2 to 4); another study showed significant benefit of a 5-mg warfarin nomogram in outpatients with VTE (RR 0.58, 95% CI 0.36 to 0.93) with NNTB = 5 (95% CI 3 to 28); a third study, consisting of both inpatients and outpatients, showed no difference (RR 1.08, 95% CI 0.65 to 1.80). No difference was observed in recurrent venous thromboembolism at 90 days when the warfarin nomogram of 10 mg was compared with the warfarin nomogram of 5 mg (RR 1.48, 95% CI 0.39 to 5.56; 3 studies, 362 participants, low quality evidence); no difference was observed in major bleeding at 14 to 90 days (RR 0.97, 95% CI 0.27 to 3.51; 4 studies, 494 participants, moderate quality evidence). No difference was observed in minor bleeding at 14 to 90 days (RR 0.52, 95% CI 0.15 to 1.83; 2 studies, 243 participants, very low quality evidence) or in length of hospital stay (mean difference (MD) -2.3 days, 95% CI -7.96 to 3.36; 1 study, 111 participants, low quality evidence). In patients with acute thromboembolism (DVT or PE) aged 18 years or older, considerable uncertainty surrounds the use of a 10-mg or a 5-mg loading dose for initiation of warfarin to achieve an INR of 2.0 to 3.0 on the fifth day of therapy. Heterogeneity among analyzed studies, mainly caused by differences in types of study participants and length of follow-up, limits certainty surrounding optimal warfarin initiation nomograms.",
        "gold": "This review of four studies with a total of 494 participants (current until June 2015) found that in patients with acute thromboembolism aged 18 years or older, considerable uncertainty surrounds the use of a 10-mg or a 5-mg loading dose for initiation of warfarin to achieve an INR of 2.0 to 3.0 on the fifth day of therapy. A benefit of 10-mg warfarin compared with 5-mg warfarin was observed for the proportion of patients with VTE who had achieved a therapeutic INR by day five but the quality of the evidence was moderate due to the differences among analyzed studies. In addition, no differences were observed between 5-mg and 10-mg nomograms for recurrent venous thromboembolism, major and minor bleeding, and length of hospital stay. Studies with high-quality evidence regarding the efficacy of 5-mg and 10-mg warfarin nomograms are needed. Quality of the evidence The quality of the evidence was moderate for therapeutic INR and major bleeding, low for recurrent VTE and length of hospital stay, and very low for minor bleeding. The main reason for downgrading the quality of the evidence was differences between the studies in types of study participants and length of follow-up."
    },
    {
        "index": "cochrane-simplification-test-100",
        "sentence": "We included seven trials with a total of 555 participants. Three trials compared models of enhanced care in the inpatient setting with conventional care. Two trials compared an enhanced care model provided in inpatient settings and at home after discharge with conventional care. Two trials compared geriatrician-led care in-hospital to conventional care led by the orthopaedic team. None of the interventions were designed specifically for people with dementia, therefore the data included in the review were from subgroups of people with dementia or cognitive impairment participating in randomised controlled trials investigating models of care for all older people following hip fracture. The end of follow-up in the trials ranged from the point of acute hospital discharge to 24 months after discharge. We considered all trials to be at high risk of bias in more than one domain. As subgroups of larger trials, the analyses lacked power to detect differences between the intervention groups. Furthermore, there were some important differences in baseline characteristics of participants between the experimental and control groups. Using the GRADE approach, we downgraded the certainty of the evidence for all outcomes to low or very low. The effect estimates for almost all comparisons were very imprecise, and the overall certainty for most results was very low. There were no data from any study for our primary outcome of health-related quality of life. There was only very low certainty for our other primary outcome, activities of daily living and functional performance, therefore we were unable to draw any conclusions with confidence. There was low-certainty that enhanced care and rehabilitation in-hospital may reduce rates of postoperative delirium (odds ratio 0.04, 95% confidence interval (CI) 0.01 to 0.22, 2 trials, n = 141) and very low-certainty associating it with lower rates of some other complications. There was also low-certainty that, compared to orthopaedic-led management, geriatrician-led management may lead to shorter hospital stays (mean difference 4.00 days, 95% CI 3.61 to 4.39, 1 trial, n = 162). We found limited evidence that some of the models of enhanced rehabilitation and care used in the included trials may show benefits over usual care for preventing delirium and reducing length of stay for people with dementia who have been treated for hip fracture. However, the certainty of these results is low. Data were available from only a small number of trials, and the certainty for all other results is very low. Determining the optimal strategies to improve outcomes for this growing population of patients should be a research priority.",
        "gold": "We searched for randomised controlled trials (a type of study in which participants are assigned to one of two or more treatment groups using a random method) that compared any model of enhanced care and rehabilitation for people with dementia after hip fracture versus the usual care provided in the trial setting. The latest search was performed on 16 October 2019. We identified seven trials that studied a total of 555 people with dementia following hip fracture. Five trials compared an enhanced interdisciplinary rehabilitation and care programme where the various healthcare professionals worked collaboratively across hospital and community settings or just in hospital, to usual hospital care. Two trials compared care in-hospital led by a geriatrician versus care led by an orthopaedic surgeon. People with dementia who receive enhanced care and rehabilitation in hospital after a hip fracture may be less likely to develop delirium. When care is led by a geriatrician, they may have stays in hospital that are three to four days shorter than if care is led by an orthopaedic surgeon. There was no information on the effect of any of the care models on quality of life, and we could not be certain about their effects on other important outcomes such as an individual's ability to manage their daily activities, regaining mobility, cognitive function, pain, death rates, or the likelihood of the person returning to the same place they had been living before the fracture. The main issues with the evidence were that most of the studies were small and their results may have been subject to bias. Most of the results of the review are very uncertain. None of the care models had been designed specifically for people with dementia. All of the data included in the review came from people with dementia who had been included in larger trials for all older people with hip fractures, although people with dementia may have particular needs. There may be some benefits from the care models studied, but the currently available research is insufficient to determine the best ways to care for people with dementia after a hip fracture operation."
    },
    {
        "index": "cochrane-simplification-test-101",
        "sentence": "We screened 4226 titles to yield seven RCTs with a total of 840 participants. Participants, interventions and outcomes were diverse. No significant differences were reported in health outcomes; two studies reported a reduction in the hospital stay with no difference in the hospital readmission rates. Three studies reported a reduction in parental anxiety and improvement in child behaviours was reported in three studies. Overall increased parental satisfaction was reported in three studies. Also, better parental coping and family functioning was reported in one study. By contrast, one study each reported no impact on parental burden of care or on functional status of children. Home care was reported as more costly for service providers with substantial cost savings for the family in two studies, while one study revealed no significant cost benefits for the family. Current research does not provide supporting evidence for a reduction in access to hospital services or a reduction in hospital readmission rate for children with acute and chronic illnesses using specialist home-based nursing services; however, the only summary finding across a few studies was that there is a significant decrease in length of hospitalisation. The preliminary results show no adverse impact on physical health outcomes and a number of papers reported improved satisfaction with home-based care. Further trials are required, measuring health, satisfaction, service utilisation and long-term costs.",
        "gold": "This review aimed to examine whether specialist paediatric home-based nursing services for children with acute and chronic illnesses reduce the number of hospital admissions and length of stay, enhance health care in the community and reduce stress for families at the time of their child's illness. It is an update of our original review published in 2006. We found seven relevant randomised controlled trials (RCTs) of total of 840 children aged from birth to 18 years with acute and/or chronic illnesses receiving either specialist home-based nursing services or conventional health care. The outcomes included use of health care services, physical and mental health, satisfaction, adverse health outcomes and costs. We decided not to combine the results of these RCTs because of the variety in types of services provided, types of participants and the outcome measures used. The results of individual RCTs show improved satisfaction with home-based care with no adverse impact on physical health outcomes for children. There is some evidence that specialist home-based nursing services reduce the length of hospital stay; however, there is no evidence that it leads to a reduction in use of hospital services. Further trials are required, measuring health, satisfaction, service use and long-term costs."
    },
    {
        "index": "cochrane-simplification-test-102",
        "sentence": "The 2016 update included two more studies (n = 196) and more publications with additional data for four already included studies. The updated review therefore includes 7524 participants from 40 randomised controlled trials (RCTs). We found data relevant to two comparisons: ICM versus standard care, and ICM versus non-ICM. The majority of studies had a high risk of selective reporting. No studies provided data for relapse or important improvement in mental state. 1. ICM versus standard care When ICM was compared with standard care for the outcome service use, ICM slightly reduced the number of days in hospital per month (n = 3595, 24 RCTs, MD -0.86, 95% CI -1.37 to -0.34,low-quality evidence). Similarly, for the outcome global state, ICM reduced the number of people leaving the trial early (n = 1798, 13 RCTs, RR 0.68, 95% CI 0.58 to 0.79, low-quality evidence). For the outcome adverse events, the evidence showed that ICM may make little or no difference in reducing death by suicide (n = 1456, 9 RCTs, RR 0.68, 95% CI 0.31 to 1.51, low-quality evidence). In addition, for the outcome social functioning, there was uncertainty about the effect of ICM on unemployment due to very low-quality evidence (n = 1129, 4 RCTs, RR 0.70, 95% CI 0.49 to 1.0, very low-quality evidence). 2. ICM versus non-ICM When ICM was compared with non-ICM for the outcome service use, there was moderate-quality evidence that ICM probably makes little or no difference in the average number of days in hospital per month (n = 2220, 21 RCTs, MD -0.08, 95% CI -0.37 to 0.21, moderate-quality evidence) or in the average number of admissions (n = 678, 1 RCT, MD -0.18, 95% CI -0.41 to 0.05, moderate-quality evidence) compared to non-ICM. Similarly, the results showed that ICM may reduce the number of participants leaving the intervention early (n = 1970, 7 RCTs, RR 0.70, 95% CI 0.52 to 0.95,low-quality evidence) and that ICM may make little or no difference in reducing death by suicide (n = 1152, 3 RCTs, RR 0.88, 95% CI 0.27 to 2.84, low-quality evidence). Finally, for the outcome social functioning, there was uncertainty about the effect of ICM on unemployment as compared to non-ICM (n = 73, 1 RCT, RR 1.46, 95% CI 0.45 to 4.74, very low-quality evidence). 3. Fidelity to ACT Within the meta-regression we found that i.) the more ICM is adherent to the ACT model, the better it is at decreasing time in hospital ('organisation fidelity' variable coefficient -0.36, 95% CI -0.66 to -0.07); and ii.) the higher the baseline hospital use in the population, the better ICM is at decreasing time in hospital ('baseline hospital use' variable coefficient -0.20, 95% CI -0.32 to -0.10). Combining both these variables within the model, 'organisation fidelity' is no longer significant, but the 'baseline hospital use' result still significantly influences time in hospital (regression coefficient -0.18, 95% CI -0.29 to -0.07, P = 0.0027). Based on very low- to moderate-quality evidence, ICM is effective in ameliorating many outcomes relevant to people with severe mental illness. Compared to standard care, ICM may reduce hospitalisation and increase retention in care. It also globally improved social functioning, although ICM's effect on mental state and quality of life remains unclear. Intensive Case Management is at least valuable to people with severe mental illnesses in the subgroup of those with a high level of hospitalisation (about four days per month in past two years). Intensive Case Management models with high fidelity to the original team organisation of ACT model were more effective at reducing time in hospital. However, it is unclear what overall gain ICM provides on top of a less formal non-ICM approach. We do not think that more trials comparing current ICM with standard care or non-ICM are justified, however we currently know of no review comparing non-ICM with standard care, and this should be undertaken.",
        "gold": "We carried out electronic searches for randomised controlled trials comparing ICM with non-ICM or standard care in 2009, 2012, and 2015. We included 40 trials involving 7524 people. The trials took place in Australia, Canada, China, Europe, and the USA. When ICM was compared to standard care, those in the ICM group were more likely to stay with the service, have improved general functioning, get a job, not be homeless, and have shorter stays in hospital (especially when they had had very long stays in hospital previously).\u00a0When ICM was compared to non-ICM, the only clear difference was that those in the ICM group were more likely to be kept in care. None of the evidence for the main outcomes of interest was high quality; at best the evidence was of moderate quality. In addition, the healthcare and social support systems of the countries where the studies took place were quite different, so it was difficult to make valid overall conclusions.\u00a0Furthermore, we were unable to use much of the data on quality of life and patient and carer satisfaction because the trials used many different scales to measure these outcomes, some of which were not validated.\u00a0 The development of an overall scale and its validation would be very beneficial in producing services that people favour. (Plain language summary initially prepared for this review by Janey Antoniou of RETHINK, UK (rethink.org))"
    },
    {
        "index": "cochrane-simplification-test-103",
        "sentence": "Twenty-five trials contributed data to the quantitative synthesis in this review. All but one trial were at high risk of bias. Overall, 16 trials (464 participants) provided data for meta-analysis of box training (248 participants) versus no supplementary training (216 participants). All the 16 trials in this comparison used video trainers. Overall, 14 trials (382 participants) provided data for quantitative comparison of different methods of box training. There were no trials comparing box model training versus animal model or cadaveric model training. Box model training versus no training: The meta-analysis showed that the time taken for task completion was significantly shorter in the box trainer group than the control group (8 trials; 249 participants; SMD -0.48 seconds; 95% CI -0.74 to -0.22). Compared with the control group, the box trainer group also had lower error score (3 trials; 69 participants; SMD -0.69; 95% CI -1.21 to -0.17), better accuracy score (3 trials; 73 participants; SMD 0.67; 95% CI 0.18 to 1.17), and better composite performance scores (SMD 0.65; 95% CI 0.42 to 0.88). Three trials reported movement distance but could not be meta-analysed as they were not in a format for meta-analysis. There was significantly lower movement distance in the box model training compared with no training in one trial, and there were no significant differences in the movement distance between the two groups in the other two trials. None of the remaining secondary outcomes such as mortality and morbidity were reported in the trials when animal models were used for assessment of training, error in movements, and trainee satisfaction. Different methods of box training: One trial (36 participants) found significantly shorter time taken to complete the task when box training was performed using a simple cardboard box trainer compared with the standard pelvic trainer (SMD -3.79 seconds; 95% CI -4.92 to -2.65). There was no significant difference in the time taken to complete the task in the remaining three comparisons (reverse alignment versus forward alignment box training; box trainer suturing versus box trainer drills; and single incision versus multiport box model training). There were no significant differences in the error score between the two groups in any of the comparisons (box trainer suturing versus box trainer drills; single incision versus multiport box model training; Z-maze box training versus U-maze box training). The only trial that reported accuracy score found significantly higher accuracy score with Z-maze box training than U-maze box training (1 trial; 16 participants; SMD 1.55; 95% CI 0.39 to 2.71). One trial (36 participants) found significantly higher composite score with simple cardboard box trainer compared with conventional pelvic trainer (SMD 0.87; 95% CI 0.19 to 1.56). Another trial (22 participants) found significantly higher composite score with reverse alignment compared with forward alignment box training (SMD 1.82; 95% CI 0.79 to 2.84). There were no significant differences in the composite score between the intervention and control groups in any of the remaining comparisons. None of the secondary outcomes were adequately reported in the trials. The results of this review are threatened by both risks of systematic errors (bias) and risks of random errors (play of chance). Laparoscopic box model training appears to improve technical skills compared with no training in trainees with no previous laparoscopic experience. The impacts of this decreased time on patients and healthcare funders in terms of improved outcomes or decreased costs are unknown. There appears to be no significant differences in the improvement of technical skills between different methods of box model training. Further well-designed trials of low risk of bias and random errors are necessary. Such trials should assess the impacts of box model training on surgical skills in both the short and long term, as well as clinical outcomes when the trainee becomes competent to operate on patients.",
        "gold": "The trials compared box model training versus no training (16 trials; 464 participants) or versus different types of box model training (14 trials; 382 participants) (some trials and participants were included in both comparisons as the trials compared different methods of box training versus no training). The primary outcomes investigated in this review were time taken to perform task, error score, accuracy score, and a composite (total summed) performance score. Box model training appears to decrease the time required to perform a laparoscopic task, improve the accuracy, decrease the errors, and improves the overall performance. This suggests that the box model training improves technical skills of surgical trainees with no previous experience in laparoscopic surgery. There does not appear to be any significant differences in different methods of box model training. The impact of the improved surgical skills on patients or healthcare funders in terms of improved health or decreased costs is unknown. All but one of the trials were of high risk of bias (defects in study design that can lead to arriving at incorrect conclusions with overestimation of benefits and underestimation of harms). Furthermore, our results are prone to risks of random errors. Overall, the quality of evidence was very low. Further well-designed trials with less risk of bias because of poor study design or because of chance are necessary."
    },
    {
        "index": "cochrane-simplification-test-104",
        "sentence": "Two randomised clinical trials were eligible for inclusion. One trial compared biliary lavage with hydrocortisone versus saline in 17 patients. Hydrocortisone tended to increase adverse events (pancreatitis, cholangitis with septicaemia, paranoid ideas, fluid retention) (RR 3.43, 95% CI 0.51 to 22.9) and had no cholangiographic improvement, which led to termination of the trial. The other trial compared budesonide versus prednisone in 18 patients. Patients had statistically significant higher serum bilirubin concentration after treatment with prednisone compared with budesonide (MD 10.4 \u00b5mol/litre, 95% CI 1.16 to 19.64 \u00b5mol/litre). No other statistically significant effects on clinical or biochemical outcomes were reported on any of the evaluated interventions. There is no evidence to support or refute peroral glucocorticosteroids for patients with primary sclerosing cholangitis. The intrabiliary application of corticosteroids via nasobiliary tube seems to induce severe adverse effects.",
        "gold": "Two trials on glucocorticosteroids for primary sclerosing cholangitis were identified. One trial compared biliary lavage with hydrocortisone versus saline. This trial was stopped due to adverse events. The other trial compared oral administration of budesonide versus prednisone. No statistically significant effects were found on mortality, serum activity of alkaline phosphatases, serum bilirubin, and adverse events for any of the evaluated intervention regimens."
    },
    {
        "index": "cochrane-simplification-test-105",
        "sentence": "A total of 11 trials were included. Seven trials addressed the timing of support (early versus delayed), data on mortality were obtained for all seven trials (284 participants). The relative risk (RR) for death with early nutritional support was 0.67 (95% CI 0.41 to 1.07). Data on disability were available for three trials. The RR for death or disability at the end of follow-up was 0.75 (95% CI 0.50 to 1.11). Seven trials compared parenteral versus enteral nutrition. Because early support often involves parenteral nutrition, three of the trials are also included in the previous analyses. Five trials (207 participants) reported mortality. The RR for mortality at the end of follow-up period was 0.66 (0.41 to 1.07). Two trials provided data on death and disability. The RR was 0.69 (95% Cl 0.40 to 1.19). One trial compared gastric versus jejunal enteral nutrition, there were no deaths and the RR was not estimable. This review suggests that early feeding may be associated with a trend towards better outcomes in terms of survival and disability. Further trials are required. These trials should report not only nutritional outcomes but also the effect on death and disability.",
        "gold": "The authors identified 11 eligible trials that investigated the timing and route of nutritional support in head-injured patients. These trials included a total of 534 patients. However, of the many of the trials had methodological weaknesses. The authors found that early feeding may be associated with fewer infections and a trend towards better outcomes in terms of survival and disability. However, the trials were small so any improvements detected were on a small scale. Also the focus of many of the trials was on nutritional outcomes, and many did not report the effect on death and disability. The authors were unable to obtain data for death and disability for all of the included trials so they feel there may be a possibility of bias. Further trials of nutritional support following head injury are required. These trials should report death and disability as well nutritional outcomes. They should also be large enough to detect clinically important treatment effects."
    },
    {
        "index": "cochrane-simplification-test-106",
        "sentence": "We included 57 studies which randomised a total of 34,390 participants. The main sources of bias were from attrition and participant blinding (36% and 21% of studies respectively, high risk of bias). Forty one studies (42 comparisons, 19,241 participants) provided data for the primary meta-analysis, which demonstrated that participants using a digital intervention drank approximately 23 g alcohol weekly (95% CI 15 to 30) (about 3 UK units) less than participants who received no or minimal interventions at end of follow up (moderate-quality evidence). Fifteen studies (16 comparisons, 10,862 participants) demonstrated that participants who engaged with digital interventions had less than one drinking day per month fewer than no intervention controls (moderate-quality evidence), 15 studies (3587 participants) showed about one binge drinking session less per month in the intervention group compared to no intervention controls (moderate-quality evidence), and in 15 studies (9791 participants) intervention participants drank one unit per occasion less than no intervention control participants (moderate-quality evidence). Only five small studies (390 participants) compared digital and face-to-face interventions. There was no difference in alcohol consumption at end of follow up (MD 0.52 g/week, 95% CI -24.59 to 25.63; low-quality evidence). Thus, digital alcohol interventions produced broadly similar outcomes in these studies. No studies reported whether any adverse effects resulted from the interventions. A median of nine BCTs were used in experimental arms (range = 1 to 22). 'B' is an estimate of effect (MD in quantity of drinking, expressed in g/week) per unit increase in the BCT, and is a way to report whether individual BCTs are linked to the effect of the intervention. The BCTs of goal setting (B -43.94, 95% CI -78.59 to -9.30), problem solving (B -48.03, 95% CI -77.79 to -18.27), information about antecedents (B -74.20, 95% CI -117.72 to -30.68), behaviour substitution (B -123.71, 95% CI -184.63 to -62.80) and credible source (B -39.89, 95% CI -72.66 to -7.11) were significantly associated with reduced alcohol consumption in unadjusted models. In a multivariable model that included BCTs with B > 23 in the unadjusted model, the BCTs of behaviour substitution (B -95.12, 95% CI -162.90 to -27.34), problem solving (B -45.92, 95% CI -90.97 to -0.87), and credible source (B -32.09, 95% CI -60.64 to -3.55) were associated with reduced alcohol consumption. The most frequently mentioned theories or models in the included studies were Motivational Interviewing Theory (7/20), Transtheoretical Model (6/20) and Social Norms Theory (6/20). Over half of the interventions (n = 21, 51%) made no mention of theory. Only two studies used theory to select participants or tailor the intervention. There was no evidence of an association between reporting theory use and intervention effectiveness. There is moderate-quality evidence that digital interventions may lower alcohol consumption, with an average reduction of up to three (UK) standard drinks per week compared to control participants. Substantial heterogeneity and risk of performance and publication bias may mean the reduction was lower. Low-quality evidence from fewer studies suggested there may be little or no difference in impact on alcohol consumption between digital and face-to-face interventions. The BCTs of behaviour substitution, problem solving and credible source were associated with the effectiveness of digital interventions to reduce alcohol consumption and warrant further investigation in an experimental context. Reporting of theory use was very limited and often unclear when present. Over half of the interventions made no reference to any theories. Limited reporting of theory use was unrelated to heterogeneity in intervention effectiveness.",
        "gold": "The studies included people in workplaces, colleges or health clinics and internet users. Everyone typed information about their drinking into a computer or mobile device - which then gave half the people advice about how much they drank and the effect this has on health. This group also received suggestions about how to cut down on drinking. The other group could sometimes read general health information. Between one month and one year later, everyone was asked to confirm how much they were drinking. Drinking levels in both groups were compared to each other at these time points. Many (56%) studies were funded by government or research foundation funds. Some (11%) were funded by personal awards such as PhD fellowships. The rest did not report sources of funding. We included 57 studies comparing the drinking of people getting advice about alcohol from computers or mobile devices with those who did not after one to 12 months. Of these, 41 studies (42 comparisons, 19,241 participants) focused on the actual amounts that people reported drinking each week. Most people reported drinking less if they received advice about alcohol from a computer or mobile device compared to people who did not get this advice. Evidence shows that the amount of alcohol people cut down may be about 1.5 pints (800 mL) of beer or a third of a bottle of wine (250 mL) each week. Other measures supported the effectiveness of digital alcohol interventions, although the size of the effect tended to be smaller than for overall alcohol consumption. Positive differences in measures of drinking were seen at 1, 6 and 12 months after the advice. There was not enough information to help us decide if advice was better from computers, telephones or the internet to reduce risky drinking. We do not know which pieces of advice were the most important to help people reduce problem drinking. However, advice from trusted people such as doctors seemed helpful, as did recommendations that people think about specific ways they could overcome problems that might prevent them from drinking less and suggestions about things to do instead of drinking. We included five studies which compared the drinking of people who got advice from computers or mobile devices with advice from face-to-face conversations with doctors or nurses; there may be little or no difference between these to reduce heavy drinking. No studies reported whether any harm came from the interventions. Personalised advice using computers or mobile devices may help people reduce heavy drinking better than doing nothing or providing only general health information. Personalised advice through computers or mobile devices may make little or no difference to reduce drinking compared to face-to-face conversation. Evidence was moderate-to-low quality."
    },
    {
        "index": "cochrane-simplification-test-107",
        "sentence": "We included 24 studies in the review with a total of 4233 participants, of which 2124 were randomised to benzodiazepines and 1475 to placebo. The remaining 634 participants were randomised to other active treatments in three-arm trials. We assessed the overall methodological quality of the included studies as poor. We rated all studies as at unclear risk of bias in at least three domains. In addition, we judged 20 of the 24 included studies as having a high risk of bias in at least one domain. Two primary outcomes of efficacy and acceptability showed a possible advantage of benzodiazepines over placebo. The estimated risk ratio (RR) for a response to treatment was 1.65 (95% confidence interval (CI) 1.39 to 1.96) in favour of benzodiazepines, which corresponds to an estimated number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 7). The dropout rate was lower among participants treated with benzodiazepines (RR 0.50, 95% CI 0.39 to 0.64); the estimated NNTB was 6 (95% CI 5 to 9). We rated the quality of the evidence as low for both primary outcomes. The possible advantage of benzodiazepine was also seen for remission (RR 1.61, 95% CI 1.38 to 1.88) and the endpoint data for social functioning (standardised mean difference (SMD) -0.53, 95% CI -0.65 to -0.42), both with low-quality evidence. We assessed the evidence for the other secondary outcomes as of very low quality. With the exception of the analyses of the change score data for depression (SMD -0.22, 95% CI -0.48 to 0.04) and social functioning (SMD -0.32, 95% CI -0.88 to 0.24), all secondary outcome analyses showed an effect in favour of benzodiazepines compared to placebo. However, the number of dropouts due to adverse effects was higher with benzodiazepines than with placebo (RR 1.58, 95% CI 1.16 to 2.15; low-quality evidence). Furthermore, our analyses of adverse events showed that a higher proportion of participants experienced at least one adverse effect when treated with benzodiazepines (RR 1.18, 95% CI 1.02 to 1.37; low-quality evidence). Low-quality evidence shows a possible superiority of benzodiazepine over placebo in the short-term treatment of panic disorders. The validity of the included studies is questionable due to possible unmasking of allocated treatments, high dropout rates, and probable publication bias. Moreover, the included studies were only short-term studies and did not examine the long-term efficacy nor the risks of dependency and withdrawal symptoms. Due to these limitations, our results regarding the efficacy of benzodiazepines versus placebo provide only limited guidance for clinical practice. Furthermore, the clinician's choice is not between benzodiazepines and placebo, but between benzodiazepines and other agents, notably SSRIs, both in terms of efficacy and adverse effects. The choice of treatment should therefore be guided by the patient's preference and should balance benefits and harms from treatment in a long-term perspective.",
        "gold": "We found consistent evidence for a possible advantage of benzodiazepines in the improvement of panic symptoms and in the number of participants dropping out of treatment. Furthermore, benzodiazepines may improve social functioning more than placebo. However, there may be more dropouts due to side effects and more participants who experience at least one side effect when treated with benzodiazepines. We found several severe limitations in the design of the included studies. For example, it seems that at least in some studies participants and physicians were able to guess to which treatment arm the participants were allocated, thus it is possible that some trials were not really blinded. These limitations may have led to an overestimation of the treatment effect. Another major limitation is that our included studies were only short-term studies and did not reflect the risks of dependency and withdrawal symptoms. Furthermore, it is unclear if the effect is maintained after the end of treatment. High-quality long-term studies should be carried out to establish whether the benefits of treatment can be maintained and to put the benefits in context of withdrawal effects and the risk of dependency. However, it is unlikely that the general conclusions regarding the short-term efficacy and the dependency potential of benzodiazepines will change. Comparisons with other active treatment including psychotherapy, for example in multiple-treatment meta-analyses, may thus be more suitable to inform clinical practise."
    },
    {
        "index": "cochrane-simplification-test-108",
        "sentence": "We identified 13 small trials (1520 participants randomised) and three ongoing trials. All studies had at least one domain with unclear risk of bias, and some studies were at high risk of bias for allocation concealment (one study) and selective reporting (two studies). Duration and style of tai chi differed between trials. Seven studies recruited 903 healthy participants, the other studies recruited people with borderline hypertension or hypertension, elderly people at high risk of falling, and people with hypertension with liver and kidney yin deficiency syndrome. No studies reported on cardiovascular mortality, all-cause mortality or non-fatal events as most studies were short term (all studies had follow-up of one year or less). There was also considerable heterogeneity between studies, which meant that it was not possible to combine studies statistically for cardiovascular risk (I2 statistic for systolic blood pressure (SBP) was 96%, for diastolic blood pressure (DBP) 96%, for total cholesterol 96%, low-density lipoprotein-cholesterol (LDL-C) 95%, high-density lipoprotein-cholesterol (HDL-C) 98%, triglycerides 75%). Nine trials measured blood pressure, six individual trials found reductions in SBP (reductions ranged from -22.0 mmHg (95% confidence interval (CI) -26.3 to -17.7) to -11.5 mmHg (95% CI -21.5 to -1.46)), two trials found no clear evidence of a difference (however, CIs were wide and an increase or decrease in SBP cannot be ruled out), and one trial found an increase in SBP with tai chi (increase 5.2 mmHg, 95% CI 3.73 to 6.67). A similar pattern was seen for DBP: three trials found a reduction in DBP (reductions ranged from -12.2 mmHg (95% CI -15.8 to -8.7) to -4.43 mmHg (95% CI -7.14 to -1.72)) and three trials found no clear evidence of a difference, however again with wide CIs. Three trials reported lipid levels and two found reductions in total cholesterol, LDL-C and triglycerides (total cholesterol reductions ranged from -1.30 mmol/L (95% CI -1.57 to -1.03) to -0.50 mmol/L (95% CI -0.74 to -0.26): LDL-C reductions ranged from -0.76 mmol/L (95% CI -0.93 to -0.59) to -0.59 mmol/L (95% CI -0.80 to -0.38): triglyceride reductions ranged from -0.46 mmol/L (95% CI -0.62 to -0.30) to -0.37 mmol/L (95% CI -0.67 to-0.07)) and increased HDL-C with the intervention (HDL-C increases ranged from 0.61 mmol/L (95% CI 0.51 to 0.71) to 0.16 mmol/L (95% CI 0.02 to 0.30)), while the third study found no clear evidence of a difference between groups on lipid levels. Quality of life was measured in one trial: tai chi improved quality of life at three months. None of the included trials reported on adverse events, costs or occurrence of type 2 diabetes. There are currently no long-term trials examining tai chi for the primary prevention of CVD. Due to the limited evidence available currently no conclusions can be drawn as to the effectiveness of tai chi on CVD risk factors. There was some suggestion of beneficial effects of tai chi on CVD risk factors but this was not consistent across all studies. There was considerable heterogeneity between the studies included in this review and studies were small and at some risk of bias. Results of the ongoing trials will add to the evidence base but additional longer-term, high-quality trials are needed.",
        "gold": "We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) looking at the effects of tai chi on adults at high risk of developing CVD. We did not included people who had already had CVD (e.g. heart attacks and strokes). The evidence is current to December 2013. We found 13 trials, none of them were large enough or of long enough duration to examine the effects of tai chi on reducing cardiovascular deaths or non-fatal endpoints. There were variations in the duration and style of tai chi and the follow-up of the interventions ranged from three to 12 months. Due to the small number of short-term studies and the variability between them, we were unable to determine conclusively whether or not tai chi was beneficial at reducing cardiovascular risk in healthy adults and adults at increased risk of CVD, although beneficial effects for CVD risk factors were seen in some studies. None of the included studies reported on adverse events. Longer-term, high-quality trials are needed in order to determine the effectiveness of tai chi for CVD prevention. The results of this review should be treated with caution as the studies were small, of short duration and there was some risk of bias (where there was a risk of arriving at the wrong conclusions because of favouritism by the participants or researchers)."
    },
    {
        "index": "cochrane-simplification-test-109",
        "sentence": "Twenty-seven RCTs were included. The interventions were very heterogeneous in the components of the family intervention, the other risk behaviours targeted alongside tobacco, the age of children at baseline and the length of follow-up. Two interventions were tested by two RCTs, one was tested by three RCTs and the remaining 20 distinct interventions were tested only by one RCT. Twenty-three interventions were tested in the USA, two in Europe, one in Australia and one in India. The control conditions fell into two main groups: no intervention or usual care; or school-based interventions provided to all participants. These two groups of studies were considered separately. Most studies had a judgement of 'unclear' for at least one risk of bias criteria, so the quality of evidence was downgraded to moderate. Although there was heterogeneity between studies there was little evidence of statistical heterogeneity in the results. We were unable to extract data from all studies in a format that allowed inclusion in a meta-analysis. There was moderate quality evidence family-based interventions had a positive impact on preventing smoking when compared to a no intervention control. Nine studies (4810 participants) reporting smoking uptake amongst baseline non-smokers could be pooled, but eight studies with about 5000 participants could not be pooled because of insufficient data. The pooled estimate detected a significant reduction in smoking behaviour in the intervention arms (risk ratio [RR] 0.76, 95% confidence interval [CI] 0.68 to 0.84). Most of these studies used intensive interventions. Estimates for the medium and low intensity subgroups were similar but confidence intervals were wide. Two studies in which some of the 4487 participants already had smoking experience at baseline did not detect evidence of effect (RR 1.04, 95% CI 0.93 to 1.17). Eight RCTs compared a combined family plus school intervention to a school intervention only. Of the three studies with data, two RCTS with outcomes for 2301 baseline never smokers detected evidence of an effect (RR 0.85, 95% CI 0.75 to 0.96) and one study with data for 1096 participants not restricted to never users at baseline also detected a benefit (RR 0.60, 95% CI 0.38 to 0.94). The other five studies with about 18,500 participants did not report data in a format allowing meta-analysis. One RCT also compared a family intervention to a school 'good behaviour' intervention and did not detect a difference between the two types of programme (RR 1.05, 95% CI 0.80 to 1.38, n = 388). No studies identified any adverse effects of intervention. There is moderate quality evidence to suggest that family-based interventions can have a positive effect on preventing children and adolescents from starting to smoke. There were more studies of high intensity programmes compared to a control group receiving no intervention, than there were for other compairsons. The evidence is therefore strongest for high intensity programmes used independently of school interventions. Programmes typically addressed family functioning, and were introduced when children were between 11 and 14 years old. Based on this moderate quality evidence a family intervention might reduce uptake or experimentation with smoking by between 16 and 32%. However, these findings should be interpreted cautiously because effect estimates could not include data from all studies. Our interpretation is that the common feature of the effective high intensity interventions was encouraging authoritative parenting (which is usually defined as showing strong interest in and care for the adolescent, often with rule setting). This is different from authoritarian parenting (do as I say) or neglectful or unsupervised parenting.",
        "gold": "We identified 27 trials; 23 in the USA and one each in Australia, India, the Netherlands, and Norway. The focus varied amongst the studies. Fifteen trials focused on substance use prevention: six focused only on tobacco prevention; one focused on alcohol; one on general substance abuse; three on tobacco, alcohol and marijuana; two on alcohol and tobacco; and two on tobacco and cardiovascular health. Two trials focused on HIV and unsafe sex prevention. Ten trials focused on family functioning, child development and modifying adolescent behaviour. Duration of follow-up after the intervention was very varied, ranging from 6 months to over 15 years for the studies which intervened with mothers of very young children. Nine trials provided data to compare a family tobacco intervention to no intervention on future smoking behaviour for those who did not smoke at the start of the study. We could not include data from a further eight trials. The results showed a significant benefit of family-based interventions over the control comparison on preventing experimentation with or taking up regular smoking. Our estimate suggested that family interventions could reduce the number of adolescents who tried smoking at all by between 16 and 32%. Two trials provided data to compare a combined family plus school intervention to a school intervention and also favoured the family-based intervention. The estimate suggested that the addition of a family intervention might reduce the onset of smoking by between 4 and 25%. We could not include data from a further five trials. Our interpretation is that the common feature of the effective interventions was encouraging authoritative parenting (which is usually defined as showing strong interest in and care for the adolescent, often with rule setting). This is different from authoritarian parenting (do as I say) or neglectful or unsupervised parenting. Because most of the randomised controlled trials included in the review did not report their methods in sufficient detail to be confident that the results were not biased, we judged the quality of the evidence to be moderate, which means that the estimate of effect is uncertain. There is moderate quality evidence that family-based interventions can prevent children and adolescents from starting to smoke. Intensive programs may be more likely to be successful than those of lower intensity. There is also evidence to suggest that adding a family-based component to a school intervention may be effective. As the interventions and settings in the review differed considerably, it is important that family-based programmes continue to be evaluated."
    },
    {
        "index": "cochrane-simplification-test-110",
        "sentence": "Three studies met the inclusion criteria, enrolling 451 participants. The trial size varied from 51 to 280 participants. Two studies compared dexamethasone to placebo, and the third study compared a number of additional interventions in various combinations, including metoclopramide, chlorpromazine, tropisetron, and dexamethasone. The duration of the studies ranged from seven to 14 days. We included two studies (127 participants) with data at eight days in the meta-analysis for nausea intensity; no data were available that incorporated the same outcome measures for the third study. Corticosteroid therapy with dexamethasone resulted in less nausea (measured on a scale of 0 to 10, with a lower score indicating less nausea) compared to placebo at eight days (MD 0.48 lower nausea, 95% CI 1.53 lower to 0.57 higher; very low-quality evidence), although this result was not statistically significant (P = 0.37). Frequency of adverse events was not significantly different between groups, and the interventions were well tolerated. Factors limiting statistical analysis included the lack of standardised measurements of nausea, and the use of different agents, dosages, and comparisons. Subgroup analysis according to type of cancer was not possible due to insufficient data. The quality of this evidence was downgraded by three levels, from high to very low due to imprecision, likely selection bias, attrition bias, and the small number of participants in the included studies. There are few studies assessing the effects of corticosteroids on nausea and vomiting not related to chemotherapy, radiotherapy, or surgery in adult cancer patients. This review found very low-quality evidence which neither supported nor refuted corticosteroid use in this setting. Further high quality studies are needed to determine if corticosteroids are efficacious in this setting.",
        "gold": "In August 2016, we found three relevant studies with 451 participants. The trial size varied from 51 to 280 participants. The duration of the included studies ranged from seven to 14 days. Two studies compared dexamethasone to placebo. The third study compared a number of additional medicines in various combinations, including metoclopramide, chlorpromazine, tropisetron, and dexamethasone. The current evidence is based on a small number of studies with a small number of participants. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low quality evidence means that we are very uncertain about the results. High quality evidence means that we are very confident in the results. We made the following conclusions from the available evidence: 1) we found very low-quality evidence of the effects of steroids on nausea and vomiting in cancer patients; 2) there was no evidence about how steroids work in different types of cancer; and 3) there were few reported side effects, and the drugs were generally well tolerated. More high quality studies are needed to determine if steroids are effective anti-nausea agents."
    },
    {
        "index": "cochrane-simplification-test-111",
        "sentence": "We included 10 RCTs of high-risk children using antibiotics (azithromycin, ciprofloxacin, co-trimoxazole, isoniazid, oral penicillin V or vancomycin) to prevent LRTIs. Three studies included HIV-infected children (n = 1345), four cystic fibrosis (n = 429) and one each sickle cell disease (n = 219), cancer (n = 160) and low birth weight neonates with underlying respiratory disorders (n = 40). The study duration ranged from seven days to three years. The quality of the evidence from studies including children with HIV infection, cystic fibrosis or cancer was moderate. Due to inadequate data, we were unable to rate the quality of the evidence for two studies: one in children with sickle cell disease (low risk of bias), and another in low birth weight neonates with underlying respiratory disorders (high risk of bias). In HIV-infected children receiving continuous isoniazid prophylaxis, there was no significant difference in the incidence of pulmonary tuberculosis (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.32 to 1.29, I2 statistic = 47%, P value = 0.21). There was no significant effect on mortality with co-trimoxazole or isoniazid prophylaxis (RR 0.82, 0.46 to 1.46, I2 statistic = 76%, P value = 0.58); however, analysis of one study that used co-trimoxazole showed a significant reduction in mortality (RR 0.67, 95% CI 0.53 to 0.85, P value = 0.001). There was a significant decrease in the rates of hospital admission per child-year of follow-up with co-trimoxazole prophylaxis in one study (P value = 0.01). There was no evidence of increased adverse events due to antibiotic prophylaxis (RR 1.10, 95% CI 0.75 to 1.64, I2 statistic = 22%, P value = 0.28); however, there was scant reporting of antibiotic resistance - the one study that did assess this found no increase. In two studies of children with cystic fibrosis receiving ciprofloxacin prophylaxis, there was no significant difference in Pseudomonas infections (RR 0.76, 0.44 to 1.31, I2 statistic = 0%, P value = 0.33). In two studies assessing the benefit of azithromycin prophylaxis, there was a significant reduction in the frequency of pulmonary exacerbations (RR 0.60, 95% CI 0.48 to 0.76, I2 statistic = 0%, P value < 0.0001). The effect of antibiotic prophylaxis on growth in children with cystic fibrosis was inconsistent across the studies. There was an increased risk of emergence of pathogenic strains with either azithromycin or ciprofloxacin prophylaxis in two studies reporting this outcome. There was no significant difference in the quality of life (one study). In three studies, there was no significant increase in the frequency of adverse events with prophylaxis with azithromycin (two studies) or ciprofloxacin (one study). There was no evidence of increased antibiotic resistance in two studies. In the one study of children with sickle cell disease, a significantly lesser proportion of children with pneumococcal septicaemia was reported with penicillin V prophylaxis (P value = 0.0025). In the one study of children with cancer there was a significant decrease in Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole prophylaxis (RR 0.03, 95% CI 0.00 to 0.47, P value < 0.01). There was no significant increase in the frequency of adverse events with antibiotic prophylaxis. In low birth weight children with underlying respiratory disorders, there was no significant difference in the proportion of children with pulmonary infection with vancomycin prophylaxis (P value = 0.18). No included studies reported time off school or carer time off work. There is inconclusive evidence that antibiotic prophylaxis in certain groups of high-risk children can reduce pneumonia, exacerbations, hospital admission and mortality in certain conditions. However, limitations in the evidence base mean more clinical trials assessing the effectiveness of antibiotics for preventing LRTIs in children at high risk should be conducted. Specifically, clinical trials assessing the effectiveness of antibiotics for preventing LRTIs in congenital heart disease, metabolic disease, endocrine and renal disorders, neurological disease or prematurity should be a priority.",
        "gold": "In February 2015, we searched for studies examining the effect of antibiotics to prevent LRTI in children aged 12 years and under with an increased risk of contracting such infections. We included 10 studies; three examined the effectiveness of antibiotics in 1345 children with HIV, four in 429 children with cystic fibrosis, one in 219 children with sickle cell disease, one in 160 children undergoing treatment for cancer, and one in 40 children who were underweight at birth with underlying breathing problems. The study duration was between 18.9 and 24.7 months for children with HIV, between six and 36 months in children with cystic fibrosis, 15 months in one study of children with sickle cell disease, 13 to 24 months in one study of children with cancer, and seven days in low birth weight newborns with underlying respiratory problems. Of three studies that included children with HIV, one was funded by an International Aid Agency, another by government and the third by a charity. Of four studies that included children with cystic fibrosis, three were funded by charities and one by government. The one study that included children with sickle cell disease was funded by government and the study that included children with cancer was funded by government, industry and charity. The funding source for the study that included newborns with underlying respiratory disorders was not specified. In children with HIV, antibiotics did not reduce the likelihood of contracting tuberculosis. Overall there was no improvement in death rates, but there was a marked reduction in hospital admission with antibiotic use in one study. In children with cystic fibrosis, antibiotics did not reduce the likelihood of infection with Pseudomonas bacteria, but there was a reduction in flare-ups, where bacterial infection makes it harder for the child to breathe. In one study of children with sickle cell disease, antibiotics reduced the likelihood of contracting blood infections. In one study of children with cancers, antibiotics reduced the likelihood of contracting Pneumocystis infection in the lungs. In low birth weight newborns with respiratory disorders, antibiotics did not reduce the likelihood of lung infections. In children with HIV, we rated the overall quality of the evidence for two studies that examined the effect of antibiotics for preventing tuberculosis as moderate because of differences in how the antibiotics were administered. We rated the quality of the evidence for antibiotic use in reducing deaths as moderate because of differences in the types of antibiotics used. Due to lack of data, we could not rate the quality of the evidence for hospital admissions. In children with cystic fibrosis, we rated the overall quality of the evidence for two studies that examined the effect of antibiotics in reducing the likelihood of Pseudomonas infection as moderate because of differences in the types of antibiotics used. We rated the quality of the evidence for the effect of antibiotics in reducing 'flare-ups' as high. In children with cancer, we rated the quality of the evidence for the effect of antibiotics in reducing the likelihood of Pneumocystis infection as moderate because of the likelihood of indirectness of the study results. Due to lack of data, we could not rate the quality of the evidence for the effect of antibiotics in reducing the likelihood of blood infections in children with sickle cell disease, or in reducing the likelihood of lung infections in low birth weight newborns with respiratory disorders; the two studies had low probability and high probability of bias respectively."
    },
    {
        "index": "cochrane-simplification-test-112",
        "sentence": "We included nine RCTs, randomising 519 participants, comparing different gases for establishing pneumoperitoneum: nitrous oxide (three trials), helium (five trials), or room air (one trial) was compared to carbon dioxide.   Three trials randomised participants to nitrous oxide pneumoperitoneum (100 participants) or carbon dioxide pneumoperitoneum (96 participants). None of the trials was at low risk of bias. There was insufficient evidence to determine the effects of nitrous oxide and carbon dioxide on cardiopulmonary complications (RR 2.00, 95% CI 0.38 to 10.43; two studies; 140 participants; very low quality of evidence), or surgical morbidity (RR 1.01, 95% CI 0.18 to 5.71; two studies; 143 participants; very low quality of evidence). There were no serious adverse events related to either nitrous oxide or carbon dioxide pneumoperitoneum (three studies; 196 participants; very low quality of evidence). We could not combine data from two trials (140 participants) which individually showed lower pain scores (a difference of about one visual analogue score on a scale of 1 to 10 with lower numbers indicating less pain) with nitrous oxide pneumoperitoneum at various time points on the first postoperative day, and this was rated asvery low quality . Four trials randomised participants to helium pneumoperitoneum (69 participants) or carbon dioxide pneumoperitoneum (75 participants) and one trial involving 33 participants did not state the number of participants in each group. None of the trials was at low risk of bias. There was insufficient evidence to determine the effects of helium or carbon dioxide on cardiopulmonary complications (RR 1.46, 95% CI 0.35 to 6.12; three studies; 128 participants; very low quality of evidence) or pain scores (visual analogue score on a scale of 1 to 10 with lower numbers indicating less pain; MD 0.49 cm, 95% CI -0.28 to 1.26; two studies; 108 participants; very low quality of evidence). There were three serious adverse events (subcutaneous emphysema) related to helium pneumoperitoneum (three studies; 128 participants; very low quality of evidence). One trial randomised participants to room air pneumoperitoneum (70 participants) or carbon dioxide pneumoperitoneum (76 participants). The trial was at unclear risk of bias. There were no cardiopulmonary complications or serious adverse events observed related to either room air or carbon dioxide pneumoperitoneum (both outcomes very low quality of evidence). The evidence of lower hospital costs and reduced pain during the first postoperative day with room air pneumoperitoneum compared with carbon dioxide pneumoperitoneum (a difference of about one visual analogue score on a scale of 1 to 10 with lower numbers indicating less pain, was rated as very low quality of evidence. The quality of the current evidence is very low. The effects of nitrous oxide and helium pneumoperitoneum compared with carbon dioxide pneumoperitoneum are uncertain. Evidence from one trial of small sample size suggests that room air pneumoperitoneum may decrease hospital costs in people undergoing laparoscopic abdominal surgery. The safety of nitrous oxide, helium, and room air pneumoperitoneum has yet to be established. Further trials on this topic are needed, and should compare various gases (i.e. nitrous oxide, helium, argon, nitrogen, and room air) with carbon dioxide under standard pressure pneumoperitoneum with cold gas insufflation for people with high anaesthetic risk. Future trials should include outcomes such as complications, serious adverse events, quality of life, and pain.",
        "gold": "We searched for all relevant studies up to September 2016. We identified nine clinical trials with 519 participants, of which three trials (196 participants) compared nitrous oxide (laughing gas) with carbon dioxide, five trials (177 participants) compared helium with carbon dioxide, and one trial (146 participants) compared room air with carbon dioxide. Studies were conducted in the USA, Australia, China, Finland, and Netherlands. The age of the participants in the trials ranged from 19 to 62 years. We are uncertain as to whether there are differences in the number of people with heart or lung complications or surgical complications between nitrous oxide and carbon dioxide. We are uncertain as to whether there are any differences in heart or lung complications, surgical complications, or pain scores between helium and carbon dioxide. There were no serious side effects related to the use of carbon dioxide, nitrous oxide, or room air, but generally serious side effects are rare events and it would take larger studies with many more participants to be sure that these gases are equally safe. There were three serious side effects when helium was used. Room air seemed to be associated with lower total hospital costs compared with carbon dioxide for insufflation of the abdominal cavity. Because of the few participants included in the review, the safety of using nitrous oxide, helium, or room air is unknown. There is no evidence for any clinical improvement by using nitrous oxide, helium, or room air instead of carbon dioxide. Overall, the quality of the evidence for the results is very low. Thus, future well-designed trials examining complications, harms, quality of life, and pain are urgently needed."
    },
    {
        "index": "cochrane-simplification-test-113",
        "sentence": "Fourteen studies were included in this review. Only RCTs investigating dexamethasone were identified. Eight studies enrolling a total of 303 participants investigated the cumulative dosage administered; three studies contrasted a high versus a moderate and five studies a moderate versus a low cumulative dexamethasone dose. Analysis of the studies investigating a moderate dexamethasone dose versus a high-dosage regimen showed an increased risk of BPD (typical risk ratio (RR) 1.50, 95% confidence interval (CI) 1.01 to 2.22; typical risk difference (RD) 0.26, 95% CI 0.03 to 0.49; number needed to treat for an additional harmful outcome (NNTH) 4, 95% CI 1.9 to 23.3; I\u00b2 = 0%, 2 studies, 55 infants) as well as an increased risk of abnormal neurodevelopmental outcome (typical RR 8.33, 95% CI 1.63 to 42.48; RD 0.30, 95% CI 0.14 to 0.46; NNTH 4, 95% CI 2.2 to 7.3; I\u00b2 = 68%, 2 studies, 74 infants) when using a moderate cumulative-dosage regimen. The composite outcomes of death or BPD and death or abnormal neurodevelopmental outcome showed similar results although the former only reached borderline significance. There were no differences in outcomes between a moderate- and a low-dosage regimen. Four other studies enrolling 762 infants investigated early initiation of dexamethasone therapy versus a moderately early or delayed initiation and showed no significant differences in the primary outcomes. The two RCTs investigating a continuous versus a pulse dexamethasone regimen showed an increased risk of the combined outcome death or BPD when using the pulse therapy. Finally, two trials investigating a standard regimen versus a participant-individualized course of dexamethasone showed no difference in the primary outcome and long-term neurodevelopmental outcomes. The quality of evidence for all comparisons discussed above was assessed as low or very low, because the validity of all comparisons is hampered by small samples of randomized infants, heterogeneity in study population and design, non-protocolized use of \u2018rescue\u2019 corticosteroids and lack of long-term neurodevelopmental data in most studies. Despite the fact that some studies reported a modulating effect of treatment regimens in favor of higher-dosage regimens on the incidence of BPD and neurodevelopmental impairment, recommendations on the optimal type of corticosteroid, the optimal dosage, or the optimal timing of initiation for the prevention of BPD in preterm infants cannot be made based on current level of evidence. A well-designed large RCT is urgently needed to establish the optimal systemic postnatal corticosteroid dosage regimen.",
        "gold": "Searching all electronic databases to 21 March 2016 revealed 14 studies investigating two or more different corticosteroid regimens in preterm infants. The investigated regimens differed in the used cumulative dose, timing of initiation and duration of therapy. Those studies comparing a high versus a lower-dosage regimen showed an increased risk of BPD and adverse neurodevelopmental outcome for infants receiving a lower cumulative dose. Those studies investigating an early versus later administration of steroids did not show any difference in outcome. Furthermore, pulse regimens showed inferior results for the outcome BPD compared with continuous treatment. An individualized dosage regimen showed no differences compared to the standard tapering course. Most of the studies had important methodological weaknesses, preventing any recommendations on the optimal corticosteroid dosage regimen for preterm infants at risk of BPD. More studies are urgently needed."
    },
    {
        "index": "cochrane-simplification-test-114",
        "sentence": "No new studies were included in this update. Eight randomised controlled trials involving 996 people were selected for inclusion in the review. Researchers compared several steroidal agents such as corticotrophin, cortisone, hydrocortisone, dexamethasone, prednisone and intravenous immunoglobulin versus aspirin, placebo or no treatment. Six trials were conducted between 1950 and 1965; one was done in 1990 and the final study was published in 2001. Overall there were no observed significant differences in risk of cardiac disease at one year between corticosteroid-treated and aspirin-treated groups (six studies, 907 participants, risk ratio 0.87, 95% confidence interval 0.66 to 1.15). Similarly, use of prednisone (two studies, 212 participants, risk ratio 1.13, 95% confidence interval 0.52 to 2.45) compared with aspirin did not reduce the risk of heart disease after one year. Investigators in five studies did not report adverse events. The three studies reporting on adverse events reported substantial adverse events. However, all results should be interpreted with caution because of the age of the studies and the substantial risk of bias. Little evidence of benefit was found when corticosteroids or intravenous immunoglobulins were used to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. In addition, risk of bias was substantial, so results should be viewed with caution. New randomised controlled trials in patients with acute rheumatic fever are warranted to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisolone and the effects of other new anti-inflammatory agents. Advances in echocardiography will allow more objective and precise assessments of cardiac outcomes.",
        "gold": "This is an update of a review published in 2003 and previously updated in 2009 and 2012. For this latest update, the search was rerun on 17 October 2013, and no new studies were found. Rheumatic fever is a late complication of a type of throat infection caused by streptococcal bacteria. It is an immune system disease that can lead to inflammatory disease of the heart (carditis), joints, brain and skin. Carditis can cause heart failure and death. Various anti-inflammatory drugs have been used to treat carditis, including corticosteroids, aspirin and immunoglobulins (immune therapy using antibodies). No new trials were identified in this update. This review includes eight trials with 996 participants. Evidence shows little effect of corticosteroids over aspirin in preventing cardiac disease after one year (six studies, 907 participants, risk ratio 0.87, 95% confidence interval 0.66 to 1.15). Several steroidal agents such as corticotrophin, cortisone, hydrocortisone and dexamethasone were compared with aspirin before 1966, and prednisone and immunoglobulins were compared with placebo in studies from 1990 and 2001, respectively. Most studies did not report on adverse events, but those that did reported complications due to corticosteroids including weight gain, enlarged facial features and acne. Trials were generally old (six of the eight trials were conducted between 1955 and 1965), small and of poor quality and had high risk of bias. For this reason, results should be interpreted with caution."
    },
    {
        "index": "cochrane-simplification-test-115",
        "sentence": "We included six studies with a total of 12,294 participants from 79 communities. Two studies that assessed insecticide spray as a fly control measure found that trachoma is reduced by at least 55% to 61% with this measure compared to no intervention. However, another study did not find insecticide spray to be effective in reducing trachoma. One study found that another fly control measure, latrine provision, reduced trachoma by 29.5% compared to no intervention; this was, however, not statistically significantly different and findings have not been confirmed by a more recent study. Another study revealed that health education reduced the incidence of trachoma. These findings were not confirmed by a second study, however,\u00a0which found that a modest health education programme with modest water supply did not reduce trachoma. However, all the studies have some methodological concerns. There is some evidence from two trials that insecticides are effective in reducing trachoma, however, this effect was not demonstrated in another trial that used insecticides. Two trials on latrine provision as a fly control measure have not demonstrated significant trachoma reduction. Health education had shown significant reduction of trachoma in one study but another study did not demonstrate similar findings. Generally there is a dearth of data to determine the effectiveness of all aspects of environmental sanitation in the control of trachoma.",
        "gold": "We included six studies involving 12,294 participants of different ages and both sexes in this review. The trials were conducted in The Gambia, Mali, Tanzania, Niger and Ethiopia. Two studies looked at insecticide spray, one looked at insecticide spray and provision of latrines, one study looked at provision of latrines, and two studies looked at health education with one of them having health education combined with water supply. Prevalence of active trachoma, prevalence of Chlamydia trachomatis and fly count measures were the main outcomes assessed. Two studies conducted in the same area found insecticide spray effective in reducing active trachoma but one study in a different setting found the spray ineffective. A separate study found health education on personal and environmental hygiene to be effective in reducing active trachoma, however, another study found that a modest health education programme combined with a modest water supply was not effective in reducing active trachoma. One study on latrine provision found no impact on trachoma. However, more research is needed."
    },
    {
        "index": "cochrane-simplification-test-116",
        "sentence": "Fifteen studies (1043 CFS participants) were included in the review. When comparing CBT with usual care (six studies, 373 participants), the difference in fatigue mean scores at post-treatment was highly significant in favour of CBT (SMD -0.39, 95% CI -0.60 to -0.19), with 40% of CBT participants (four studies, 371 participants) showing clinical response in contrast with 26% in usual care (OR 0.47, 95% CI 0.29 to 0.76). Findings at follow-up were inconsistent. For CBT versus other psychological therapies, comprising relaxation, counselling and education/support (four studies, 313 participants), the difference in fatigue mean scores at post-treatment favoured CBT (SMD -0.43, 95% CI -0.65 to -0.20). Findings at follow-up were heterogeneous and inconsistent. Only two studies compared CBT against other interventions and one study compared CBT in combination with other interventions against usual care. CBT is effective in reducing the symptoms of fatigue at post-treatment compared with usual care, and may be more effective in reducing fatigue symptoms compared with other psychological therapies. The evidence base at follow-up is limited to a small group of studies with inconsistent findings. There is a lack of evidence on the comparative effectiveness of CBT alone or in combination with other treatments, and further studies are required to inform the development of effective treatment programmes for people with CFS.",
        "gold": "This review aimed to find out whether CBT is effective for CBT, both as a standalone treatment and in combination with other treatments, and whether it is more effective than other treatments used for CFS. The review included 15 studies, with a total of 1043 CFS participants. The review showed that people attending for CBT were more likely to have reduced fatigue symptoms at the end of treatment than people who received usual care or were on a waiting list for therapy, with 40% of people in the CBT group showing clinical improvement, in contrast with 26% in usual care. At follow-up, 1-7 months after treatment ended, people who had completed their course of CBT continued to have lower fatigue levels, but when including people who had dropped out of treatment, there was no difference between CBT and usual care. The review also compared CBT against other types of psychological therapy, including relaxation techniques, counselling and support/education, and found that people attending for CBT was more likely to have reduced fatigue symptoms at the end of treatment than those attending for other psychological therapies. Physical functioning, depression, anxiety and psychological distress symptoms were also more reduced when compared with other psychological therapies. However at follow-up, the results were inconsistent and the studies did not fit well together, making it difficult to draw any conclusions. Very few studies reported on the acceptability of CBT and no studies examined side effects. Only two studies compared the effectiveness of CBT against other treatments, both exercise therapy, and just one study compared a combination of CBT and other treatments with usual care. More studies should be carried out to establish whether CBT is more helpful than other treatments for CFS, and whether CBT in combination with other treatments is more helpful than single treatment approaches."
    },
    {
        "index": "cochrane-simplification-test-117",
        "sentence": "One double-blind randomised controlled study including 46 people with sickle cell disease (HbSS, HbSC, HbS\u03b2+thal and HbS\u03b20thal) was eligible for inclusion in this review. Of the 46 enrolled participants, seven withdrew before randomisation leaving 39 participants who were randomised. Only 25 participants completed the full six months of follow up. Participants were randomised to receive oral vitamin D3 (cholecalciferol) (n = 20) or placebo (n = 19) for six weeks and were followed up to six months. Two participants from the treatment group have missing values of baseline serum 25-hydroxyvitamin D, therefore the number of samples analysed was 37 (vitamin D n = 18, placebo n = 19). The included study had a high risk of bias with regards to incomplete outcome data (high dropout rate in the placebo group), but a low risk of bias for other domains such as random sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, selective outcome reporting; and an unclear risk of other biases. Compared to the placebo group, the vitamin D group had significantly higher serum 25-hydroxyvitamin D (25(OH)D) levels at eight weeks, mean difference 29.79 (95% confidence interval 26.63 to 32.95); at 16 weeks, mean difference 12.67 (95% confidence interval 10.43 to 14.90); and at 24 weeks, mean difference 15.52 (95% confidence interval 13.50 to 17.54). We determined the quality of the evidence for this outcome to be moderate. There was no significant difference of adverse events (tingling of lips or hands) between the vitamin D and placebo groups, risk ratio 3.16 (95% confidence interval 0.14 to 72.84), but the quality of the evidence was low. Regarding the frequency of pain, the vitamin D group had significantly fewer pain days compared to the placebo group, mean difference -10.00 (95% confidence interval -16.47 to -3.53), but again the quality of the evidence was low. Furthermore, the review included physical functioning PedsQL scores which was reported as absolute change from baseline. The vitamin D group had a lower (worse) health-related quality of life score than the placebo group but this was not significant at eight weeks, mean difference -2.02 (95% confidence interval -6.34 to 2.30). However, the difference was significant at both 16 weeks, mean difference -12.56 (95% confidence interval -16.44 to -8.69) and 24 weeks, mean difference -12.59 (95% confidence interval -17.43 to -7.76). We determined the quality of evidence for this outcome to be low. We included only one low-quality clinical study which had a high risk of bias with regards to incomplete outcome data. Therefore, we consider that the evidence is not of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider the relevant existing guidelines for vitamin D supplementation (e.g. the Endocrine Society Clinical Practice Guidelines) and dietary reference intakes for calcium and vitamin D (e.g. from the USA Institute of Medicine). Evidence of vitamin D supplementation in sickle cell disease from high quality studies is needed. Well-designed, randomised, placebo-controlled studies of parallel design, are required to determine the effects and the safety of vitamin D supplementation in children and adults with sickle cell disease.",
        "gold": "The review included one study which recruited 46 people with sickle cell disease aged between seven and 21 years; of these 39 people in the study were randomly selected to take vitamin D tablets or placebo tablets for six weeks and then followed up for six months. The study reported results from 37 people. People taking a vitamin D supplement had higher levels of vitamin D in their blood when it was measured after eight, 16 and 24 weeks. There were no differences in the number of people reporting side effects, such as tingling in the lips or hands between the vitamin D group and the placebo group. The vitamin D group had fewer days of pain compared to the placebo group. The study also reported on health-related quality of life (physical functioning scores). After eight weeks the vitamin D group had a slightly worse score than the placebo group, but the difference was much greater after 16 and 24 weeks. Given these results from this small single study with moderate to low quality of the evidence, we do not think the results of our review are of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider relevant existing guidelines for vitamin D supplementation (e.g. the Endocrine Society Clinical Practice Guidelines), and recommendations for calcium and vitamin D intake (from e.g. the USA Institute of Medicine). High-quality studies looking at the effects of supplementing vitamin D in children and adults with sickle cell disease are needed. We do not think there are risks of bias in the way people were put into the different groups and we do not think anyone (either the participant or the doctor) could guess which group they were in once the study started. Even though the adverse events were not reported in the original report, the study author provided the information upon request. More people dropped out of the placebo group (68.4%) than the vitamin D group (5%), and two people assigned to vitamin D group but not included in the analysis. We considered there was a high risk of bias in the way the study reported results. The evidence is only applicable to people with sickle cell disease when they are in a steady state, i.e. at least 30 days from blood transfusion and at least 14 days from any acute sickle complication. The quality of evidence for the outcomes ranged from moderate to low. We considered the quality of the evidence for vitamin D blood levels to be moderate, and for adverse events, days of pain and health-related quality of life, the quality of the evidence was low."
    },
    {
        "index": "cochrane-simplification-test-118",
        "sentence": "This review includes only one RCT, funded by the Australian Research Council; the University of Sydney International Development Fund; Douglas and Lola Douglas Scholarship on Child and Adolescent Health; Nadia Verrall Memorial Scholarship; and a James Kentley Memorial Fellowship. This study recruited 26 children aged 4 to 12 years, with mild to moderate CAS of unknown cause, and compared two interventions: the Nuffield Dyspraxia Programme-3 (NDP-3); and the Rapid Syllable Transitions Treatment (ReST). Children were allocated randomly to one of the two treatments. Treatments were delivered intensively in one-hour sessions, four days a week for three weeks, in a university clinic in Australia. Speech pathology students delivered the treatments in the English language. Outcomes were assessed before therapy, immediately after therapy, at one month and four months post-therapy. Our review looked at one-month post-therapy outcomes only. A number of cases in each cohort had recommenced usual treatment by their speech and language pathologist between one month and four months post-treatment (NDP-3: 9/13 participants; ReST: 9/13 participants). Hence, maintenance of treatment effects to four months post-treatment could not be analysed without significant potential bias, and thus this time point was not included for further analysis in this review. We judged all core outcome domains to be low risk of bias. We downgraded the quality of the evidence by one level to moderate due to imprecision, given that only one RCT was identified. Both the NDP-3 and ReST therapies demonstrated improvement at one month post-treatment. For three outcomes the effect was marginally greater for NDP-3 than ReST: accuracy of production on treated words (NDP-3 mean difference (MD) = 36.0, ReST MD = 33.9; absolute MD = 2.1 between groups); speech production consistency, measured by 25 real words repeated three times using the inconsistency subtest of the Diagnostic Evaluation of Articulation and Phonology (DEAP) test (NDP-3 MD = 11.1, ReST MD = 10.9; absolute MD = 0.2 between groups); and accuracy of connected speech, assessed by imitated word accuracy in connected speech of at least three word combinations (NDP-3 MD = 14.3, ReST MD = 11.5; absolute MD = 2.8 between groups). ReST (MD = 18.3) demonstrated a marginally greater effect than NDP-3 (MD = 18.2) for accuracy of production on non-treated words at one month post-treatment (absolute MD = 0.1 between groups). The study did not assess the outcome of functional communication. There is limited evidence that, when delivered intensively, both NDP-3 and ReST may effect improvement in word accuracy in 4- to 12-year-old children with CAS, measured by the accuracy of production on treated and non-treated words, speech production consistency and the accuracy of connected speech. The study did not measure functional communication. No formal analyses were conducted to compare NDP-3 and ReST by the original study authors, hence one treatment cannot be reliably advocated over the other. We are also unable to say whether either treatment is better than no treatment or treatment as usual. No evidence currently exists to support the effectiveness of other treatments for children aged 4 to 12 years with idiopathic CAS without other comorbid neurodevelopmental disorders. Further RCTs replicating this study would strengthen the evidence base. Similarly, further RCTs are needed of other interventions, in other age ranges and populations with CAS and with co-occurring disorders.",
        "gold": "We found one study with 26 children aged 4 to 12 years with CAS. The children had mild to severe CAS without a known cause. Children were allocated randomly (using a method like coin tossing) to one of two treatments: the Nuffield Dyspraxia Programme - Third Edition (NDP-3); and the Rapid Syllable Transition treatment (ReST). Both therapies were delivered intensively in one-hour sessions, four days a week for three weeks. The treatments were delivered by speech pathology students in a university clinic. Outcomes were assessed before therapy, immediately after therapy, at one month and four months post-therapy. Our review looked at one-month post-therapy outcomes only. The included study was funded by the Australian Research Council; the University of Sydney International Development Fund; Douglas & Lola Douglas Scholarship on Child and Adolescent Health; Nadia Verrall Memorial Scholarship; and a James Kentley Memorial Fellowship. Further studies replicating these findings would strengthen available evidence. The study provides limited evidence that the NDP-3 may improve the accuracy of production on treated items and the accuracy of connected speech. There is limited evidence that the NDP-3 has a negligible effect on speech production consistency, and the ReST a negligible effect on accuracy of production on non-treated words. The study did not measure functional communication. The included study was a randomised controlled trial with an overall low risk of bias. We downgraded the quality of the evidence by one level to moderate, due to imprecision, given that only one RCT was identified. There is limited evidence that the NDP-3 or ReST may be helpful for children with CAS of unknown origin, aged 4 to 12 years, without other co-occurring conditions. We were not able to find out whether one of these treatment was better than the other, or whether either was better than no treatment or treatment as usual. There is currently no available evidence for other treatments. Further RCTs \u2014 including studies comparing treatments to a no-treatment (wait-list) control group \u2014 would strengthen the evidence base. Further research is also needed for children with CAS and other disorders or diagnoses."
    },
    {
        "index": "cochrane-simplification-test-119",
        "sentence": "Four trials that randomised a total of 268 participants met the inclusion criteria. In all four studies antibiotic was administered orally. One study conducted in Brazil in both adults and children compared trimethoprim-sulfamexacocol over 20 months to no treatment and was judged to be at high risk of performance, detection, and attrition bias. The other three studies compared antibiotic treatment to placebo. We judged these three studies to be at a mixture of low or unclear risk of bias due to poor reporting. One study conducted in the US in adults studied pyrimethamine-trisulfapyrimidine for eight weeks; one study conducted in the UK in children and adults evaluated pyrimethamine for four weeks; and one study conducted in Brazil in adults investigated trimethoprim-sulfamethoxazole for 12 months. In the last study, all participants had active retinochoroiditis and were treated with antibiotics for 45 days prior to randomisation to trimethoprim-sulfamethoxazole versus placebo. Only the study in Brazil of trimethoprim-sulfamethoxazole over 12 months, in participants with healed lesions, reported the effect of treatment on visual acuity. People treated with antibiotics may have a similar change in visual acuity compared with people treated with placebo at one year (mean difference -1.00 letters, 95% confidence interval (CI) -7.93 to 5.93 letters; 93 participants; low-quality evidence). Treatment with antibiotics probably reduces the risk of recurrent retinochoroiditis compared with placebo (risk ratio (RR) 0.26, 95% CI 0.11 to 0.63; 227 participants; 3 studies; I2 = 0%; moderate-quality evidence); similar results were seen for acute and chronic retinochoroiditis. The UK study of pyrimethamine for four weeks reported an improvement in intraocular inflammation in treated compared with control participants (RR 1.76, 95% CI 0.98 to 3.19; 29 participants; low-quality evidence). The study in Brazil of trimethoprim-sulfamethoxazole for 12 months stated that the severity of inflammation was higher in the comparator group when compared to the antibiotic-treated group but did not provide further details. In the US study of pyrimethamine-trisulfapyrimidine for eight weeks intraocular inflammation had almost completely resolved by eight weeks in all participants, however in this study all participants received steroid treatment. Two studies (UK and US studies) reported an increased risk of adverse events in treated participants. These were a fall in haemoglobin, leucocyte, and platelet count, nausea, loss of appetite, rash, and arthralgia. Treatment with antibiotics probably reduces the risk of recurrent toxoplasma retinochoroiditis, but there is currently no good evidence that this leads to better visual outcomes. However, absence of evidence of effect is not the same as evidence of no effect. Further trials of people with acute and chronic toxoplasma retinochoroiditis affecting any part of the retina are required to determine the effects of antibiotic treatment on visual outcomes.",
        "gold": "We found four studies with a total of 268 participants. These studies were conducted in Brazil, the UK, and the US. The evidence is current to 22 February 2016. Only one of the four studies compared the effect of antibiotic treatment for 12 months with placebo on visual acuity and found similar changes in both groups. Three studies examined the effect of antibiotics on reducing the number of recurring episodes of the disease. Two of these three studies were conducted in Brazil in adults infected with the more aggressive South American strains of the parasite, which can cause frequently recurring eye symptoms. The studies from Brazil found that the long-term antibiotics over 14 and 12 months, respectively, reduced the number of recurrent episodes of retinochoroiditis. The other study did not find that short-term (eight weeks) treatment with antibiotics made any difference. Two studies reported an improvement in intraocular inflammation in antibiotic-treated compared with untreated participants, and one study reported no changes. Two studies investigated side effects of giving antibiotics such as decreased white blood cells, loss of appetite, rashes and other allergic reactions and found only weak evidence that antibiotics increase the risk of side effects. There were problems with the design, conduct, and analyses of all of the studies, which could have biased the results. There was a lack of evidence about whether antibiotics (short or long term) prevent vision loss. More trials are needed, including trials of newer antibiotics."
    },
    {
        "index": "cochrane-simplification-test-120",
        "sentence": "We included 43 trials containing predominantly older people with mainly trochanteric fractures.   Twenty-two trials (3749 participants) compared the Gamma nail with the sliding hip screw (SHS). The Gamma nail was associated with increased risk of operative and later fracture of the femur and increased reoperation rate. There were no major differences between implants in wound infection, mortality or medical complications. Five trials (623 participants) compared the intramedullary hip screw (IMHS) with the SHS. Fracture fixation complications were more common in the IMHS group. Results for post-operative complications, mortality and functional outcomes were similar in both groups. Three trials (394 participants) showed no difference in fracture fixation complications, reoperation, wound infection and length of hospital stay for proximal femoral nail (PFN) versus the SHS. None of the 10 trials (1491 participants) of other nail versus extramedullary implant comparisons for trochanteric fractures provided sufficient evidence to establish definite differences between the implants under test. Two trials (65 participants) found intramedullary nails were associated with fewer fracture fixation complications than fixed nail plates for unstable fractures at the level of the lesser trochanter. Two trials (124 participants) found a tendency to less fracture healing complications with the intramedullary nails compared with fixed nail plates for subtrochanteric fractures. With its lower complication rate in comparison with intramedullary nails, and absence of functional outcome data to the contrary, the SHS appears superior for trochanteric fractures. Further studies are required to confirm whether more recently developed designs of intramedullary nail avoid the complications of previous nails. Intramedullary nails may have advantages over fixed angle plates for subtrochanteric and some unstable trochanteric fractures, but further studies are required.",
        "gold": "The main results were for the comparisons of various types of intramedullary nails with the sliding hip screw. Twenty-two trials, involving 3749 participants, tested the Gamma nail. Five trials, involving 623 participants, tested the intramedullary hip screw (IMHS). Three trials, involving 394 participants, tested the proximal femoral nail. Other trials involved newer varieties of intramedullary nails. Most older trials showed a tendency for the nails to be associated with an increased risk of fracture of the thigh bone both during and after the operation. More recent trials testing newer varieties of nails seemed to avoid this specific problem to some extent. The review found that using intramedullary nails resulted in one extra reoperation in every 50 people. Mortality and, where data were available, other long-term outcomes were similar between the implants. The review concluded that current evidence supports the continued use of the sliding hip screw for fixing the more common types of extracapsular hip fractures. This may not be the case for some of the more recently developed designs of intramedullary nails or for specific fracture types, but further research is required to confirm this."
    },
    {
        "index": "cochrane-simplification-test-121",
        "sentence": "The search strategy identified 183 unique references of which 22 were identified as being potentially eligible on the basis of title and abstract. Only one study met our inclusion criteria and was included in the review. It analysed retrospective data for 47 women who received either palliative surgery (n = 27) or medical management with Octreotide (n = 20) and reported overall survival and perioperative mortality and morbidity. Women with poor performance status were excluded from surgery. Although six (22%) women who received surgery had serious complications of the operation and three (11%) died of complications, multivariable analysis found that women who received surgery had significantly (p < 0.001) better survival than women who received Octreotide, after adjustment for important prognostic factors. However, the magnitude of this effect was not reported. Quality of life (QoL) was not reported and adverse events were incompletely documented. We found only low quality evidence comparing palliative surgery and medical management for bowel obstruction in ovarian cancer. Therefore we are unable to reach definite conclusions about the relative benefits and harms of the two forms of treatment, or to identify sub-groups of women who are likely to benefit from one treatment or the other. However, there is weak evidence in support of surgical management to prolong survival.",
        "gold": "We found only one relevant study. It included only 47 cases: 27 had an operation to relieve bowel obstruction and the 20 who did not have an operation were given a drug called Octreotide to control the amount of vomiting that often results from bowel obstruction. Among the 27 women who had an operation, six women could not have their bowel obstruction corrected because the cancer had spread too far, six women had serious complications of surgery and three died of these complications. \u00a0Nevertheless, the authors of the study reported that women who had the operation survived longer, on average, than those who did not, even after allowing for their underlying better health. It was unclear how much of the difference in survival could be ascribed to the differences in treatment and how much to the better health of women undergoing surgery. Unfortunately the study did not assess their QoL or level of pain. The study reported the numbers of women who could start eating again after their treatment (surgery or Octreotide) but it didn't analyse this allowing for the underlying difference in health of women in the two groups, so it is impossible to interpret these results. We were therefore unable to reach definite conclusions about the relative benefits and harms of the two forms of treatment and we were unable to identify sub-groups of women who are likely to benefit from one treatment or the other."
    },
    {
        "index": "cochrane-simplification-test-122",
        "sentence": "Four trials fulfilled the criteria for inclusion. They comprised a total of 244 women with PCOS receiving 12 weeks or 6 weeks of treatment. Two trials (184 women randomised) studied the effects of simvastatin and two trials (60 women randomised) studied the effects of atorvastatin. There was no good evidence that statins improved menstrual regularity, spontaneous ovulation rate, hirsutism or acne, either alone or in combination with the combined oral contraceptive pill (OCP). Nor were there any significant effects on body mass index (BMI). Statins were effective in lowering testosterone levels (nmol/L) (mean difference (MD) -0.90, 95% CI -1.18 to -0.62, P < 0.00001, 3 RCTs, 105 women) when used alone or with the OCP. Statins also improved total cholesterol, low-density lipoprotein (LDL) and triglycerides but had no significant effect on high-density lipoprotein (HDL) levels, high sensitivity (HS) C-reactive protein (HS-CRP), fasting insulin or homeostatic model assessment (HOMA) insulin resistance. No serious adverse events were reported in any of the included studies. Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well-designed RCTs to assess clinical outcomes.",
        "gold": "There is no good evidence from this review that statins improve menstrual regularity, spontaneous ovulation rate, hirsutism or acne, either alone or in combination with the combined oral contraceptive pill. There is also no good evidence that statins have a beneficial effect on hirsutism or acne (pimples) associated with PCOS. In women with PCOS, statins are effective in reducing serum androgen levels and decreasing bad cholesterol (LDL), but statins are not effective in reducing fasting insulin or insulin resistance. There is no good evidence available on the long-term use of statins (alone or in combination) for the management of PCOS."
    },
    {
        "index": "cochrane-simplification-test-123",
        "sentence": "The search strategy identified 1522 unique references of which we excluded 1330 on the basis of title and abstract. We retrieved the remaining 22 articles in full, but none satisfied the inclusion criteria. We identified only observational data from single-arm studies of women treated with formalin-soaked packs, interventional radiology or radiotherapy techniques for palliative control of vaginal bleeding in women with cervical cancer. Since the last version of this review we found no new studies. There is no evidence from controlled trials to support or refute the use of any of the proposed interventions compared with radiotherapy. Therefore, the choice of intervention will be based on local resources. Radiotherapy techniques for managing vaginal bleeding are not readily available in resource-poor settings, where advanced cases of cervical cancer are predominant. Thus, this systematic review identified the need for a randomised controlled trial assessing the benefits and risks of palliative treatments for vaginal bleeding in women with advanced cervical cancer.",
        "gold": "the searches were updated to March 2018. We found no randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) for inclusion, so there is an absence of evidence that tranexamic acid, vaginal packing (with or without formalin-soaked packs), interventional radiology techniques or other interventions are as effective or safe as radiotherapy for palliative control of bleeding from the vagina in advanced cervical cancer. There is a need for randomised controlled trials or good-quality non-randomised comparative studies to determine the effectiveness and safety of these interventions when compared with radiotherapy in terms of symptom control, quality of life and side events. no studies fulfilled the inclusion criteria and so there is no good-certainty evidence."
    },
    {
        "index": "cochrane-simplification-test-124",
        "sentence": "For primary therapy three RCTs were identified, enrolling a total of 745 patients, that investigated temozolomide in combination with radiotherapy versus radiotherapy alone for glioblastoma multiforme (GBM). Temozolomide increased OS (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.46 to 0.79, P value 0.0003) and increased PFS (HR 0.63, 95% CI 0.43 to 0.92, P value 0.02), when compared with radiotherapy alone, although these benefits only appear to emerge when therapy is given in both concomitant and adjuvant phases of treatment. A single RCT found that temozolomide did not have a statistically significant effect on QoL. Risk of haematological complications, fatigue and infections were increased with temozolomide. In recurrent HGG, two RCTs enrolling 672 patients in total found that temozolomide did not increase OS compared to standard chemotherapy (HR 0.9, 95% CI 0.76 to 1.06, P value 0.2) but it did increase PFS in a subgroup analysis of grade IV GBM tumours (HR 0.68, 95% CI 0.51 to 0.90, P value 0.008). Adverse events were similar between arms. In the elderly, 2 RCTs of 664 patients found OS and PFS was similar with temozolomide alone versus radiotherapy alone. QoL did not appear to differ between arms in a single trial but certain adverse events were significantly more common with temozolomide. Temozolomide when given in both concomitant and adjuvant phases is an effective primary therapy in GBM compared to radiotherapy alone. It prolongs survival and delays progression without impacting on QoL but it does increase early adverse events. In recurrent GBM, temozolomide compared with standard chemotherapy improves time-to-progression (TTP) and may have benefits on QoL without increasing adverse events but it does not improve overall. In the elderly, temozolomide alone appears comparable to radiotherapy in terms of OS and PFS but with a higher instance of adverse events.",
        "gold": "Three randomised controlled trials (RCTs) enrolling patients with newly diagnosed glioblastoma multiforme (GBM - a form of HGG) have studied chemotherapy with temozolomide during and after radiotherapy. This was compared with radiotherapy only. Those who received temozolomide had an improved survival and delayed progression of the disease. The short-term adverse events associated with temozolomide are low but can be severe, while the long-term effects are unknown. No RCTs investigated the use of temozolomide in HGGs other than GBM. In recurrent GBM, temozolomide delayed progression but did not improve overall survival. In the elderly population (age over 60 years), temozolomide alone appears to be a suitable alternative to radiotherapy alone for primary therapy of GBM. Either treatment has similar overall survival, progression-free survival and quality of life, but there are possibly more adverse events with temozolomide. All these trials enrolled highly selected patients with good prognostic features that are not entirely representative of all patients with HGG limiting the general applicability of these results."
    },
    {
        "index": "cochrane-simplification-test-125",
        "sentence": "Two studies met our inclusion criteria. The findings of one study conducted in Cambodia provide low quality evidence that private contracts with international nongovernmental organizations (NGOs) for district health systems management ('contracting-in') may improve health care access and utilization. Contracting-in increased use of antenatal care by 28% and use of public facilities by 14%. However, contracting-in was not found to have an effect on population health outcomes. The findings of the other study provide low quality evidence that intermittent training courses over 18 months may improve district health system managers\u2019 performance. In three countries in Latin America, managers who did not receive the intermittent training courses had between 2.4 and 8.3 times more management deficiencies than managers who received the training courses. No studies that aimed to investigate interventions for retaining district health systems managers met our study selection criteria for inclusion in this review. There is low quality evidence that contracting-in may improve health care accessibility and utilization and that intermittent training courses may improve district health systems managers\u2019 performance. More evidence is required before firm conclusions can be drawn regarding the effectiveness of these interventions in diverse settings. Other interventions that might be promising candidates for hiring and retaining (e.g., government regulations, professional support programs) as well as training district health systems managers (e.g., in-service workshops with on-site support) have not been adequately investigated.",
        "gold": "It is difficult to draw any conclusions about the effects of these types of interventions as the review only found two relevant studies. In addition, the evidence that the review did identify was of low quality. Training: The available evidence suggests that in-service district manager training: \u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 may lead to more knowledge about planning processes \u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 may lead to better monitoring and evaluation skills None of the studies assessed the effects of district manager training on people\u2019s health, on their access to or use of health care, or on the quality or efficiency of care. Contracting-in: The available evidence suggests that private contracts with international NGOs for district health systems management: \u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 may not affect people\u2019s illness reporting, diarrhea incidence or infant death \u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 may increase the likelihood that a health facility is open 24 hours \u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 may increase the availability of medical equipment and supplies \u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 may increase people\u2019s use of antenatal care and public facilities None of the studies assessed the effects of contracting-in district management on the quality or efficiency of health care, on job vacancy rates, or on district manager knowledge and skills."
    },
    {
        "index": "cochrane-simplification-test-126",
        "sentence": "We included three studies that involved 123 people. The methods used for blinding the participants and researchers to the treatment group were not reported, but as the comparison is surgical treatment with medical treatment this bias is hard to avoid. There was no description of concealment of the randomization sequence in two studies. All three studies reported on mortality, and deaths occurred in two studies. There was no clear evidence of a difference in mortality between treatment groups (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.13 to 2.42); however, the analysis was underpowered to detect a difference between groups. Out of the 123 people randomized and treated, six people died; the causes of death were pneumonia, pulmonary embolism, mediastinitis, and septic shock. Among people randomized to surgery, there were reductions in pneumonia (RR 0.36, 95% 0.15 to 0.85; three studies, 123 participants), chest deformity (RR 0.13, 95% CI 0.03 to 0.67; two studies, 86 participants), and tracheostomy (RR 0.38, 95% CI 0.14 to 1.02; two studies, 83 participants). Duration of mechanical ventilation, length of intensive care unit stay (ICU), and length of hospital stay were measured in the three studies. Due to differences in reporting, we could not combine the results and have listed them separately. Chest pain, chest tightness, bodily pain, and adverse effects were each measured in one study. There was some evidence from three small studies that showed surgical treatment was preferable to nonsurgical management in reducing pneumonia, chest deformity, tracheostomy, duration of mechanical ventilation, and length of ICU stay. Further well-designed studies with a sufficient sample size are required to confirm these results and to detect possible surgical effects on mortality.",
        "gold": "We searched scientific databases for studies comparing surgical treatment with nonsurgical treatment in adults or children with flail chest. We included three studies in this review, which involved 123 people. In these studies, people with flail chest were randomly allocated into the surgery or no surgery study groups. The results show that surgery to repair the broken ribs reduces pneumonia, chest deformity, tracheostomy, duration of mechanical ventilation and length of ICU stay. There was no difference in deaths between people treated with surgery or no surgery. Since only six people died across the three studies, due to a variety of causes, more research is needed in order to know for certain which treatment is better for reducing deaths. These three small studies have shown that surgical treatment is preferable to nonsurgical treatment in reducing pneumonia, chest deformity, tracheostomy, mechanical ventilation and length of stay in the ICU. More research is needed in order to know which treatment is better for reducing deaths. Three more studies are being undertaken by researchers in the USA and Canada at the moment, and the results will be incorporated into the review in the future."
    },
    {
        "index": "cochrane-simplification-test-127",
        "sentence": "Fifty trials (19 RCTs and 31 before-and-after studies) evaluated the dose-related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any age with and without cardiovascular disease and the trials studied cerivastatin effects within a treatment period of three to 12 weeks. Cerivastatin 0.025 mg/day to 0.8 mg/day caused LDL cholesterol decreases of 11.0% to 40.8%, total cholesterol decreases of 8.0% to 28.8% and triglyceride decreases of 9.0% to 21.4%. We judged the certainty of evidence for these effects to be high. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on LDL cholesterol, total cholesterol and triglycerides. When compared to fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin at reducing LDL cholesterol; 233-fold more potent than fluvastatin, 18-fold more potent than atorvastatin and six-fold more potent than rosuvastatin at reducing total cholesterol; and 125-fold more potent than fluvastatin, 11-fold more potent than atorvastatin and 13-fold more potent than rosuvastatin at reducing triglycerides. There was no dose-related effect of cerivastatin on HDL cholesterol, but overall cerivastatin increased HDL cholesterol by 5%. There was a high risk of bias for the outcome withdrawals due to adverse effects, but a low risk of bias for the lipid measurements. Withdrawals due to adverse effects were not different between cerivastatin and placebo in 11 of 19 of these short-term trials (risk ratio 1.09, 95% confidence interval 0.68 to 1.74). The LDL cholesterol, total cholesterol, and triglyceride lowering effect of cerivastatin was linearly dependent on dose. Cerivastatin log dose-response data were linear over the commonly prescribed dose range. Based on an informal comparison with fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin in reducing LDL cholesterol, and 233-fold greater potency than fluvastatin, 18-fold greater potency than atorvastatin and six-fold greater potency than rosuvastatin at reducing total cholesterol. This review did not provide a good estimate of the incidence of harms associated with cerivastatin because of the short duration of the trials and the lack of reporting of adverse effects in 42% of the RCTs.",
        "gold": "We looked for high quality randomised trials (RCTs) and before-and-after studies with cerivastatin in\u00a0different dose sizes\u00a0. The trials were between three and twelve\u00a0weeks long. People of any age and gender, either with or without heart disease were in these trials. Participants could be of any age and gender, with or without cardiovascular disease. We found fifty trials with 13,018 participants who had their lipid levels measured. 12,877 participants had their LDL cholesterol measured. People taking 0.025 to 0.8 mg of\u00a0cerivastatin per\u00a0day\u00a0lowered their LDL cholesterol by 12% to 42%. The higher the dose,\u00a0the lower the levels of three measures of\u00a0cholesterol. HDL cholesterol increased by 5%. For lowering\u00a0LDL cholesterol, cerivastatin is 250-times\u00a0stronger than fluvastatin, 20-times\u00a0stronger than atorvastatin and 5.5 times stronger than rosuvastatin. Only 11 of the 19 RCTs reported the number of people who dropped out of the studies because of adverse effects. The level of drop outs due to adverse effects were similar in the people who took cerivastatin and placebo. There is a high level of trust\u00a0around the results\u00a0 for total cholesterol and LDL cholesterol and very low to moderate for triglycerides. We have a low level of trust in the evidence around drop outs because many (8 out of 19 trials) did not report drop outs due to adverse effects."
    },
    {
        "index": "cochrane-simplification-test-128",
        "sentence": "We included 28 studies which randomised a total of 6851 patients. Risk of bias assessment indicated unclear to low risk of bias for most studies. For consistency regarding the direction of effects, continuous outcomes with negative values, and dichotomous outcomes with values less than one favour remote ischaemic preconditioning. Based on high quality evidence, remote ischaemic preconditioning made little or no difference to the reduction of serum creatinine levels at postoperative days one (14 studies, 1022 participants: MD -0.02 mg/dL, 95% CI -0.05 to 0.02; I2 = 21%), two (9 studies, 770 participants: MD -0.04 mg/dL, 95% CI -0.09 to 0.02; I2 = 31%), and three (6 studies, 417 participants: MD -0.05 mg/dL, 95% CI -0.19 to 0.10; I2 = 68%) compared to control. Serious adverse events occurred in four patients receiving remote ischaemic preconditioning by iliac clamping. It is uncertain whether remote ischaemic preconditioning by cuff inflation leads to increased adverse effects compared to control because the certainty of the evidence is low (15 studies, 3993 participants: RR 3.47, 95% CI 0.55 to 21.76; I2 = 0%); only two of 15 studies reported any adverse effects (6/1999 in the remote ischaemic preconditioning group and 1/1994 in the control group), the remaining 13 studies stated no adverse effects were observed in either group. Compared to control, remote ischaemic preconditioning made little or no difference to the need for dialysis (13 studies, 2417 participants: RR 0.85, 95% CI 0.37 to 1.94; I2 = 60%; moderate quality evidence), length of hospital stay (8 studies, 920 participants: MD 0.17 days, 95% CI -0.46 to 0.80; I2 = 49%, high quality evidence), or all-cause mortality (24 studies, 4931 participants: RR 0.86, 95% CI 0.54 to 1.37; I2 = 0%, high quality evidence). Remote ischaemic preconditioning may have slightly improved the incidence of acute kidney injury using either the AKIN (8 studies, 2364 participants: RR 0.76, 95% CI 0.57 to 1.00; I2 = 61%, high quality evidence) or RIFLE criteria (3 studies, 1586 participants: RR 0.91, 95% CI 0.75 to 1.12; I2 = 0%, moderate quality evidence). Remote ischaemic preconditioning by cuff inflation appears to be a safe method, and probably leads to little or no difference in serum creatinine, adverse effects, need for dialysis, length of hospital stay, death and in the incidence of acute kidney injury. Overall we had moderate-high certainty evidence however the available data does not confirm the efficacy of remote ischaemic preconditioning in reducing renal ischaemia reperfusion injury in patients undergoing major cardiac and vascular surgery in which renal ischaemia reperfusion injury may occur.",
        "gold": "We performed a search off all available literature on 8 August 2016 to find all randomised controlled studies. 28 studies including 6851 patients were included in this analysis. Five studies included children undergoing cardiac surgery. Adult studies included patients undergoing major vascular surgery (three studies), cardiac surgery (nine studies), coronary bypass surgery (10 studies) and partial kidney resection (one study). The overall quality of the studies was acceptable. Twenty studies were funded without economical interest. One study was funded from a source with commercial interest. The other seven studies did not report funding. Remote ischaemic preconditioning performed with a blood pressure cuff appears to be safe as only two of 15 studies reported adverse effects (6/1999 in the remote ischaemic preconditioning group and 1/1994 in the control group). However remote ischaemic preconditioning by vascular clamping may cause vascular complications. Kidney injury in patients undergoing (surgical) procedures in which kidney injury may occur, was not reduced by remote Ischaemic preconditioning measured at day one, two or three after surgery. The need for dialysis, hospital stay and death were not reduced by remote ischaemic preconditioning. Although remote ischaemic preconditioning by cuff inflation is safe, available data do not confirm the efficacy of remote ischaemic preconditioning in reducing kidney injury."
    },
    {
        "index": "cochrane-simplification-test-129",
        "sentence": "We retrieved 12,490 citations, obtained full texts for 58 studies and included 12 trials (three from the 2008 search and nine from the 2014 search) with 703 participants. Eight trials primarily investigated the efficacy in treating PSF, of which six trials with seven comparisons provided data suitable for meta-analysis (five pharmacological interventions: fluoxetine, enerion, (-)-OSU6162, citicoline and a combination of Chinese herbs; and two non-pharmacological interventions: a fatigue education programme and a mindfulness-based stress reduction programme). The fatigue severity was lower in the intervention groups than in the control groups (244 participants, pooled SMD -1.07, 95% confidence interval (CI) -1.93 to -0.21), with significant heterogeneity between trials (I2 = 87%, degrees of freedom (df) = 6, P value < 0.00001). The beneficial effect was not seen in trials that had used adequate allocation concealment (two trials, 89 participants, SMD -0.38, 95% CI -0.80 to 0.04) or trials that had used adequate blinding of outcome assessors (four trials, 198 participants, SMD -1.10, 95% CI -2.31 to 0.11). No trial primarily investigated the efficacy in preventing PSF. Four trials (248 participants) did not primarily investigate the efficacy on fatigue but other symptoms after stroke. None of these interventions showed any benefit on reducing PSF, which included tirilazad mesylate, continuous positive airway pressure for sleep apnoea, antidepressants and a self management programme for recovery from chronic diseases. There was insufficient evidence on the efficacy of any intervention to treat or prevent fatigue after stroke. Trials to date have been small and heterogeneous, and some have had a high risk of bias. Some of the interventions described were feasible in people with stroke, but their efficacy should be investigated in RCTs with a more robust study design and adequate sample sizes.",
        "gold": "The evidence is current to May 2014. We found 12 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 703 people with stroke. Of these 12 trials, eight trials recruited only people with fatigue and were primarily intended to treat fatigue, no trial was primarily intended to prevent fatigue and the other four trials were not primarily intended to treat or prevent fatigue but reported fatigue as an outcome. There was insufficient evidence to support the use of any intervention to treat or prevent fatigue in people with stroke. The general study quality was low. The available data were limited as each identified intervention was only investigated in a single trial. In addition, some trials were small and used poor study designs. Therefore, further trials of better quality are needed."
    },
    {
        "index": "cochrane-simplification-test-130",
        "sentence": "Three randomised trials, enrolling 74 preterm infants (outcome data available on 71 infants) evaluated interventions for hyperkalaemia. Urine output was ascertained in only one study (Hu 1999). In none of the trials could we ascertain that allocation to the comparison groups was concealed. The sample sizes of the three trials were very small with 12 (Malone 1991), 19 (Singh 2002) and 40 infants enrolled (Hu 1999). The intervention and the outcome assessments could not be blinded to the clinical staff in two trials (Malone 1991; Hu 1999). One study (Malone 1991), glucose and insulin, compared to cation-exchange resin, caused a reduction in all cause mortality that was of borderline statistical significance: RR 0.18 (95% CI 0.03 to 1.15); RD -0.66 (95% CI -1.09 to -0.22); NNTB 2 (95% CI 1 to 5)]. In the study of Hu (Hu 1999), the incidence of intraventricular haemorrhage \u2265 grade 2 was significantly reduced [RR 0.30 (95% CI 0.10 to 0.93); RD -0.35 (95% CI -0.62 to -0.08); NNTB 3 (95% CI 2 to 13). Albuterol inhalation versus saline inhalation changed serum K+ from baseline at four hours [WMD -0.69 mmol/L (95% CI -0.87 to -0.51)] and at eight hours [WMD -0.59 mmol/L (95% CI -0.78 to -0.40)] after initiation of treatment. No differences noted in mortality or other clinical outcomes (Singh 2002). No serious side effects were noted with either the combination of insulin and glucose or albuterol inhalation. Other interventions listed in our objectives have not been studied to date. In view of the limited information from small studies of uncertain quality, no firm recommendations for clinical practice can be made. It appears that the combination of insulin and glucose is preferred over treatment with rectal cation-resin for hyperkalaemia in preterm infants. Both the combination of insulin and glucose and albuterol inhalation deserve further study. The two interventions could possibly be tested against each other. The effectiveness of other potentially effective interventions for non-oliguric hyperkalaemia (diuretics, exchange transfusion, peritoneal dialysis and calcium) have not been tested in randomised controlled trials.",
        "gold": "The objective of this review was to determine the effectiveness and safety of interventions for this serious condition. Two studies enrolling 52 infants that assessed the use of a combination of insulin and sugar to reduce the blood levels of potassium were identified. This combination reduced the duration of high blood levels of potassium and the risk for bleeds in the brains of the infants. One study that enrolled 19 patients reported on the use of albuterol (a medication that helps to move potassium from the blood to the body cells). Albuterol lowered the blood levels of potassium both at four and at eight hours after the treatment had started. Because of the few infants enrolled in the studies to date, no firm recommendations for the treatment of too high blood levels of potassium in neonates can be made. Further research is needed."
    },
    {
        "index": "cochrane-simplification-test-131",
        "sentence": "Twelve trials were found to be eligible for inclusion in this review. Seven trials with a variable risk of bias compared IVIg with PE in 623 severely affected participants. In five trials with 536 participants for whom the outcome was available, the mean difference (MD) of change in a seven-grade disability scale after four weeks was not significantly different between the two treatments: MD of 0.02 of a grade more improvement in the intravenous immunoglobulin than the plasma exchange group; 95% confidence interval (CI) 0.25 to -0.20. There were also no statistically significant differences in the other measures considered. Three studies including a total of 75 children suggested that IVIg significantly hastens recovery compared with supportive care. The primary outcome for this review, available for only one trial with 21 mildly affected children, showed significantly more improvement in disability grade after four weeks with IVIg than supportive treatment alone, MD 1.42, 95% CI 2.57 to 0.27. In one trial involving 249 participants comparing PE followed by IVIg with PE alone, the mean grade improvement was 0.2 (95% CI -0.14 to 0.54) more in the combined treatment group than in the PE alone group; not clinically significantly different, but not excluding the possibility of significant extra benefit. Another trial with 34 participants comparing immunoabsorption followed by IVIg with immunoabsorption alone did not reveal significant extra benefit from the combined treatment. Adverse events were not significantly more frequent with either treatment, but IVIg is significantly much more likely to be completed than PE. One trial in altogether 51 children showed no significant difference when the standard dose was given over two days rather than five days. A previous Cochrane review has shown that PE hastens recovery compared with supportive treatment alone. There are no adequate comparisons of IVIg with placebo in adults, but this review provides moderate quality evidence that, in severe disease, IVIg started within two weeks from onset hastens recovery as much as PE. Adverse events were not significantly more frequent with either treatment but IVIg is significantly much more likely to be completed than PE. Also, according to moderate quality evidence, giving IVIg after PE did not confer significant extra benefit. In children, according to low quality evidence, IVIg probably hastens recovery compared with supportive care alone. More research is needed in mild disease and in patients whose treatment starts more than two weeks after onset. Dose-ranging studies are also needed and one is in progress.",
        "gold": "We included trials of IVIg compared to no treatment, dummy treatment, PE, immunoabsorption (in which specific antibodies are removed from blood) or other immune treatments. We also considered trials of IVIg added to another treatment. We found 12 trials. Some of these compared more than two treatments. - Seven trials compared IVIg with PE (in 623 participants with severe GBS). - One compared PE alone to PE followed by IVIg (in 249 participants). - Three compared IVIg with supportive care (in a total of 75 children). - One compared a two-day to a five-day IVIg treatment plan (in 51 children). - One compared IVIg with immunoabsorption (in 48 participants). - One compared IVIg plus immunoabsorption with immunoabsorption (in 34 participants). For this review, we chose change in a disability scale after four weeks\u2019 treatment as the main measure of the effect of IVIg. Five of the trials comparing IVIg and PE measured change in disability. IVIg and PE produced a similar amount of improvement in disability in the 536 trial participants. This evidence was of moderate quality. Harmful effects were no more frequent with PE or IVIg, but people were more likely to finish a course of IVIg. In one trial involving 249 participants who received PE or PE followed by IVIg, there was slightly more improvement from PE and IVIg together. The effect was probably not large enough to be noticeable but the results do not rule out the possibility. This evidence was of moderate quality. Three studies in children suggested that IVIg speeds up recovery compared with supportive care. Only one used the disability scale. They provided low quality evidence. In one small trial in children, the effect on disability appeared similar with a standard dose over two days rather than five days. Giving IVIg after immunoabsorption provided no extra benefit over immunoabsorption alone. No conclusions can be drawn from the trial comparing IVIg with immunoabsorption. The risk of bias in the included studies was variable. More research is needed to find the best dose of IVIg in adults and children, and one trial of giving a second dose to people who otherwise would be expected to do badly is in progress. The evidence is current to December 2013."
    },
    {
        "index": "cochrane-simplification-test-132",
        "sentence": "We included 28 randomized clinical trials (9330 participants); in the 21 trials reporting relevant outcomes for this review, 7597 participants were randomly assigned to a high fraction of inspired oxygen versus a routine fraction of inspired oxygen. In trials with an overall low risk of bias, a high fraction of inspired oxygen compared with a routine fraction of inspired oxygen was not associated with all-cause mortality (random-effects model: RR 1.12, 95% confidence interval (CI) 0.93 to 1.36; GRADE: low quality) within the longest follow-up and within 30 days of follow-up (Peto odds ratio (OR) 0.99, 95% CI 0.61 to 1.60; GRADE: low quality). In a trial sequential analysis, the required information size was not reached and the analysis could not refute a 20% increase in mortality. Similarly, when all trials were included, a high fraction of inspired oxygen was not associated with all-cause mortality to the longest follow-up (RR 1.07, 95% CI 0.87 to 1.33) or within 30 days of follow-up (Peto OR 0.83, 95% CI 0.54 to 1.29), both of very low quality according to GRADE. Neither was a high fraction of inspired oxygen associated with the risk of surgical site infection in trials with low risk of bias (RR 0.86, 95% CI 0.63 to 1.17; GRADE: low quality) or in all trials (RR 0.87, 95% CI 0.71 to 1.07; GRADE: low quality). A high fraction of inspired oxygen was not associated with respiratory insufficiency (RR 1.25, 95% CI 0.79 to 1.99), serious adverse events (RR 0.96, 95% CI 0.65 to 1.43) or length of stay (mean difference -0.06 days, 95% CI -0.44 to 0.32 days). In subgroup analyses of nine trials using preoperative antibiotics, a high fraction of inspired oxygen was associated with a decrease in surgical site infections (RR 0.76, 95% CI 0.60 to 0.97; GRADE: very low quality); a similar effect was noted in the five trials adequately blinded for the outcome assessment (RR 0.79, 95% CI 0.66 to 0.96; GRADE: very low quality). We did not observe an effect of a high fraction of inspired oxygen on surgical site infections in any other subgroup analyses. As the risk of adverse events, including mortality, may be increased by a fraction of inspired oxygen of 60% or higher, and as robust evidence is lacking for a beneficial effect of a fraction of inspired oxygen of 60% or higher on surgical site infection, our overall results suggest that evidence is insufficient to support the routine use of a high fraction of inspired oxygen during anaesthesia and surgery. Given the risk of attrition and outcome reporting bias, as well as other weaknesses in the available evidence, further randomized clinical trials with low risk of bias in all bias domains, including a large sample size and long-term follow-up, are warranted.",
        "gold": "We identified 28 randomized clinical trials. Eight trials with 4918 participants reported on risk of death, and 15 trials with 7219 participants reported on surgical site infections within 14 to 30 days of surgery. Four trials reported serious adverse events, three trials respiratory insufficiency, nine trials length of stay during the associated hospital admission and one trial quality of life. All trials were conducted without direct industry funding. The number of participants in each trial ranged from 38 to 2012. The mean age of participants was 50 years (range 15 to 92 years) and 63% were women. Types of surgery included abdominal surgery (eight trials), caesarean section (four trials), breast surgery (one trial), orthopaedic surgery (two trials) and various other surgical procedures (four trials). A high percentage of inspired oxygen was not statistically associated with increased risk of death, or with a decrease in surgical site infections, in all trials that measured these outcomes, in trials of highest quality and in those with longest follow-up. An increased risk of adverse events could not be proved right or wrong for a high percentage of inspired oxygen during anaesthesia and surgery. Only five of the included trials had low risk of bias. The trials randomly assigned 9330 participants, of whom only 7537 participants provided data for this review. The number of participants required to detect or reject a 20% relative risk reduction in deaths was not reached; therefore the observed results were uncertain."
    },
    {
        "index": "cochrane-simplification-test-133",
        "sentence": "Twenty-five trials (3663 children) were eligible for inclusion. Two trials did not report on any of the outcomes of interest, leaving 23 trials (3258 children) covering a range of antibiotics, participants, outcome measures and time points for evaluation. Overall, we assessed most studies as being at low to moderate risk of bias. We found moderate quality evidence (six trials including 484 children) that children treated with oral antibiotics are more likely to have complete resolution at two to three months post-randomisation (primary outcome) than those allocated to the control treatment (risk ratio (RR) 2.00, 95% confidence interval (CI) 1.58 to 2.53; number needed to treat to benefit (NNTB) 5). However, there is evidence (albeit of low quality; five trials, 742 children) indicating that children treated with oral antibiotics are more likely to experience diarrhoea, vomiting or skin rash (primary outcome) than those allocated to control treatment (RR 2.15, 95% CI 1.29 to 3.60; number needed to treat to harm (NNTH) 20). In respect of the secondary outcome of complete resolution at any time point, we found low to moderate quality evidence from five meta-analyses, including between two and 14 trials, of a beneficial effect of antibiotics, with a NNTB ranging from 3 to 7. Time periods ranged from 10 to 14 days to six months. In terms of other secondary outcomes, only two trials (849 children) reported on hearing levels at two to four weeks and found conflicting results. None of the trials reported data on speech, language and cognitive development or quality of life. Low quality evidence did not show that oral antibiotics were associated with a decrease in the rate of ventilation tube insertion (two trials, 121 children) or in tympanic membrane sequelae (one trial, 103 children), while low quality evidence indicated that children treated with antibiotics were less likely to have acute otitis media episodes within four to eight weeks (five trials, 1086 children; NNTB 18) and within six months post-randomisation (two trials, 199 children; NNTB 5). It should, however, be noted that the beneficial effect of oral antibiotics on acute otitis media episodes within four to eight weeks was no longer significant when we excluded studies with high risk of bias. This review presents evidence of both benefits and harms associated with the use of oral antibiotics to treat children up to 16 years with OME. Although evidence indicates that oral antibiotics are associated with an increased chance of complete resolution of OME at various time points, we also found evidence that these children are more likely to experience diarrhoea, vomiting or skin rash. The impact of antibiotics on short-term hearing is uncertain and low quality evidence did not show that oral antibiotics were associated with fewer ventilation tube insertions. Furthermore, we found no data on the impact of antibiotics on other important outcomes such as speech, language and cognitive development or quality of life. Even in situations where clear and relevant benefits of oral antibiotics have been demonstrated, these must always be carefully balanced against adverse effects and the emergence of bacterial resistance. This has specifically been linked to the widespread use of antibiotics for common conditions such as otitis media.",
        "gold": "This review included evidence available up to 14 April 2016. In total 25 studies (3663 children) were eligible for inclusion. Two studies did not report on any of the outcomes of interest, leaving 23 studies (3258 children). Overall, we assessed most studies as being at low to moderate risk of bias. In the 23 studies many different antibiotics were used and the children were of different ages and had suffered from glue ear for various lengths of time. They looked at the benefits at various time points after the treatment was given. The most important outcomes that we measured were the difference in the proportion of children who no longer had glue ear two to three months after the treatment was started and adverse effects of antibiotics (diarrhoea, vomiting or skin rash). We found moderate quality evidence (six trials including 484 children) that children treated with oral antibiotics are more likely to have glue ear resolved two to three months after the treatment was started than those allocated to control treatment. The number of children needed to treat for one beneficial outcome (NNTB) was five. However, there is evidence (albeit of low quality; five trials, 742 children) indicating that children treated with oral antibiotics are more likely to experience diarrhoea, vomiting or skin rash than those allocated to control treatment. The number of children needed to treat for one harmful outcome (NNTH) was 20. In respect of the secondary outcome of having glue ear resolved at any time point, we found low to moderate quality evidence from five of our analyses where we combined data from studies (meta-analyses), which included between two and 14 studies, of a beneficial effect of antibiotics, with a NNTB ranging from three to seven. Time periods ranged from 10 to 14 days to six months. In terms of other secondary outcomes, only two trials (849 children) reported on hearing levels at two to four weeks and found conflicting results. None of the trials reported data on speech, language and cognitive development or quality of life. Low quality evidence did not show that oral antibiotics were associated with fewer ventilation tube (grommet) insertions (two trials, 121 children) or in adverse consequences for the tympanic membrane (ear drum) (one trial, 103 children). Low quality evidence indicated that children treated with oral antibiotics were less likely to have acute otitis media (ear infection) episodes within four to eight weeks (five trials, 1086 children; NNTB 18) and within six months after treatment was started (two trials, 199 children; NNTB 5). It should however be noted that the beneficial effect of oral antibiotics on ear infection episodes within four to eight weeks was no longer significant when studies with high risk of bias were excluded. Moderate quality evidence is available that children with glue ear do benefit from oral antibiotics in terms of resolving glue ear at various time points and reducing acute otitis media episodes during follow-up compared with control treatment. Low quality evidence is available that children treated with oral antibiotics are more likely to experience diarrhoea, vomiting and skin rash than those receiving the control treatment. Currently only two trials have assessed the impact of oral antibiotics on hearing and these showed conflicting results (low quality evidence). Low quality evidence did not show that oral antibiotics were associated with fewer ventilation tube insertions or in adverse consequences for the tympanic membrane."
    },
    {
        "index": "cochrane-simplification-test-134",
        "sentence": "Twelve studies were included, nine RCTs and three before and after studies. Only one study explored all-cause mortality and end-stage renal disease (ESRD) as endpoints. The relative risk (RR) of ESRD or death was 0.23 (95% confidence interval (CI) 0.07 to 0.72) for patients assigned to a low protein diet (LPD). Pooling of the seven RCTs in patients with type 1 diabetes resulted in a non-significant reduction in the decline of glomerular filtration rate (GFR) of 0.1 ml/min/month (95% CI -0.1 to 0.3) in the LPD group. For type 2 diabetes, one trial showed a small insignificant improvement in the rate of decline of GFR in the protein-restricted group and a second found a similar decline in both the intervention and control groups. Actual protein intake in the intervention groups ranged from 0.7 to 1.1 g/kg/day. One study noted malnutrition in the LPD group. We found no data on the effects of LPDs on health-related quality of life and costs. The results show that reducing protein intake appears to slightly slow progression to renal failure but not statistically significantly so. However, questions concerning the level of protein intake and compliance remain. Further longer-term research on large representative groups of patients with both type 1 and type 2 diabetes mellitus is necessary. Because of the variability amongst patients, there might perhaps be a six month therapeutic trial of protein restriction in all individuals, with continuation only in those who responded best. Trials are required of different types of protein.",
        "gold": "Based on 12 studies, including from eight to 160 people with type 1 and type 2 diabetes for at least an average four-month period, restricted protein intake appeared to slow progression of diabetic kidney disease, but not by much on average. However, individual variation existed, therefore a low-protein diet may benefit some individuals. A low-protein diet can be difficult to adhere to, especially over the long term. Reducing the amount of animal protein is the usual method but some evidence suggests that a shift from red meat to white meat and fish or vegetables may give similar results. We found no data on the effects of low-protein diet on health-related quality of life and costs."
    },
    {
        "index": "cochrane-simplification-test-135",
        "sentence": "We identified a total of 19 studies involving 3480 people. Twelve studies were of good methodological quality and seven were of lower quality, according to the van Tulder scoring system. Within the subgroup of predominantly mild brain injury, 'strong evidence' suggested that most individuals made a good recovery when appropriate information was provided, without the need for additional specific interventions. For moderate to severe injury, 'strong evidence' showed benefit from formal intervention, and 'limited evidence' indicated that commencing rehabilitation early after injury results in better outcomes. For participants with moderate to severe ABI already in rehabilitation, 'strong evidence' revealed that more intensive programmes are associated with earlier functional gains, and 'moderate evidence' suggested that continued outpatient therapy could help to sustain gains made in early post-acute rehabilitation. The context of multi-disciplinary rehabilitation appears to influence outcomes. 'Strong evidence' supports the use of a milieu-oriented model for patients with severe brain injury, in which comprehensive cognitive rehabilitation takes place in a therapeutic environment and involves a peer group of patients. 'Limited evidence' shows that specialist in-patient rehabilitation and specialist multi-disciplinary community rehabilitation may provide additional functional gains, but studies serve to highlight the particular practical and ethical restraints imposed on randomisation of severely affected individuals for whom no realistic alternatives to specialist intervention are available. Problems following ABI vary. Consequently, different interventions and combinations of interventions are required to meet the needs of patients with different problems. Patients who present acutely to hospital with mild brain injury benefit from follow-up and appropriate information and advice. Those with moderate to severe brain injury benefit from routine follow-up so their needs for rehabilitation can be assessed. Intensive intervention appears to lead to earlier gains, and earlier intervention whilst still in emergency and acute care has been supported by limited evidence. The balance between intensity and cost-effectiveness has yet to be determined. Patients discharged from in-patient rehabilitation benefit from access to out-patient or community-based services appropriate to their needs. Group-based rehabilitation in a therapeutic milieu (where patients undergo neuropsychological rehabilitation in a therapeutic environment with a peer group of individuals facing similar challenges) represents an effective approach for patients requiring neuropsychological rehabilitation following severe brain injury. Not all questions in rehabilitation can be addressed by randomised controlled trials or other experimental approaches. For example, trial-based literature does not tell us which treatments work best for which patients over the long term, and which models of service represent value for money in the context of life-long care. In the future, such questions will need to be considered alongside practice-based evidence gathered from large systematic longitudinal cohort studies conducted in the context of routine clinical practice.",
        "gold": "Studies eligible for inclusion in this review were controlled trials, in which one group of people received treatment (such as MD rehabilitation) and was compared with a similar group that received a different treatment. We found 19 relevant studies, which involved a total of 3480 people. We searched the medical literature worldwide on 14 September 2015. We used the Van Tulder system to rate the strength of the evidence as it distinguished better between trials of different quality than the standard GRADE system on criteria that are important in the context of rehabilitation. For mild brain injury, information and advice were usually more appropriate than intensive rehabilitation. As a whole, studies suggest that patients with moderate to severe brain injury who received more intensive rehabilitation showed earlier improvement, and that earlier rehabilitation was better than delayed treatment. Strong evidence supports the provision of cognitive rehabilitation in a therapeutic 'milieu', that is, an environment in which patients receive predominantly group-based rehabilitation alongside a peer group of others who are facing similar challenges. Trial-based literature provided little evidence related to other aspects of MD rehabilitation, so the review authors recommend that additional research should be done. Rehabilitation for brain injury is such an individualised and long-term process that research studies do not necessarily facilitate general conclusions. Overall the included studies were of good quality; 12 of 19 studies were judged to be of high quality according to the van Tulder scoring system. The other studies were at risk of bias because of elements of their design, for example, in one study, treatment depended on the availability of a bed in the rehabilitation unit. Bed availability is a haphazard way of allocating treatment to patients, and this makes results of the study prone to bias."
    },
    {
        "index": "cochrane-simplification-test-136",
        "sentence": "We included one trial (involving 176 women) in this review. This trial included four groups with a factorial design. The factorial design took into account two factors, i.e. infant location in relation to the mother and the type of infant apparel. We combined three of the groups as the intervention (rooming-in) group and the fourth group acted as the control (separate care) and we analysed the results as a single pair-wise comparison. Primary outcomes The primary outcome, duration of any breastfeeding, was reported by authors as median values because the distribution was found to be skewed. They reported the overall median duration of any breastfeeding to be four months, with no difference found between groups. Duration of exclusive breastfeeding and the proportion of infants being exclusively breastfed at six months of age was not reported in the trial. There was no difference found between the two groups in the proportion of infants receiving any breastfeeding at six months of age (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.51 to 1.39; one trial; 137 women; low-quality evidence). Secondary outcomes The mean frequency of breastfeeds per day on day four postpartum for the rooming-in group was 8.3 (standard deviation (SD) 2.2), slightly higher than the separate care group, i.e. seven times per day. However, between-group comparison of this outcome was not appropriate since every infant in the separate care group was breastfed at a fixed schedule of seven times per day (SD = 0) resulting in no estimable comparison. The rate of exclusive breastfeeding on day four postpartum before discharge from hospital was significantly higher in the rooming-in group 86% (99 of 115) compared with separate care group, 45% (17 of 38), (RR 1.92; 95% CI 1.34 to 2.76; one trial, 153 women; low-quality evidence). None of our other pre-specified secondary outcomes were reported. We found little evidence to support or refute the practice of rooming-in versus mother-infant separation. Further well-designed RCTs to investigate full mother-infant rooming-in versus partial rooming-in or separate care including all important outcomes are needed.",
        "gold": "The latest search was done on 30th May 2016. No new studies were identified. Only one study is included in the review. One trial (involving 176 women) was analysed which provided information on the rate of exclusive breastfeeding on discharge from hospital. We found that there was low-quality evidence that keeping mother and infant together in the same room after birth until they are discharged from the hospital increased the rate of exclusive breastfeeding at four days after birth. There was no difference between the groups in the proportion of infants receiving any breastfeeding at six months of age. We found little evidence to support or refute the practice of rooming-in after birth. A randomised controlled trial is needed and it should report all important outcomes, including breastfeeding duration."
    },
    {
        "index": "cochrane-simplification-test-137",
        "sentence": "Eight trials involving 660 participants were included. Seven of the eight studies were of poor quality. Follow-up time was less than one month in six trials. Only two trials provided data for the number of participants who were dead or dependent at the end of 28 days of treatment, indicating a significantly lower rate of death and dependency in the sanchi group than in the control group (relative risk (RR) 0.63, 95% confidence interval (Cl) 0.45 to 0.88). One trial reported higher Barthel index scores in the sanchi group. Pooled analysis of seven trials indicated that sanchi might improve neurological deficit more than control with a significant difference (RR 0.29, 95%Cl 0.18 to 0.47). The total case fatality rate was lower than 1% indicating that participants probably had mild strokes. Few adverse events were reported. Data were limited in respect of stroke recurrence and quality of life. Sanchi appears to be beneficial and safe for acute ischaemic stroke in this review, but the small sample and inferior quality of studies prevented a definite conclusion. More well-designed randomised controlled trials are required.",
        "gold": "This review of eight trials, involving 660 participants, indicated that sanchi improved short-term outcome. However, the evidence from the small sample size and inferior quality of the studies does not support its routine use for acute ischaemic stroke. Well-designed trials are required."
    },
    {
        "index": "cochrane-simplification-test-138",
        "sentence": "Fourteen eligible RCTs were identified but only seven trials could be included. Four RCTs evaluated implant placement timing. Two RCTs compared immediate versus delayed implants in 126 patients and found no statistically significant differences. One RCT compared immediate-delayed versus delayed implants in 46 patients. After 2 years patients in the immediate-delayed group perceived the time to functional loading significantly shorter, were more satisfied and independent blinded assessor judged the level of the perimplant marginal mucosa in relation to that of the adjacent teeth as more appropriate (RR = 1.68; 95% CI 1.04 to 2.72). These differences disappeared 5 years after loading but significantly more complications occurred in the immediate-delayed group (RR = 4.20; 95% CI 1.01 to 17.43). One RCT compared immediate with immediately delayed implants in 16 patients for 2 years and found no differences. Three RCTs evaluated different techniques of bone grafting for implants immediately placed in extraction sockets. No statistically significant difference was observed when evaluating whether autogenous bone is needed in postextractive sites (1 trial with 26 patients) or which was the most effective augmentation technique (2 trials with 56 patients). There is insufficient evidence to determine possible advantages or disadvantages of immediate, immediate-delayed or delayed implants, therefore these preliminary conclusions are based on few underpowered trials often judged to be at high risk of bias. There is a suggestion that immediate and immediate-delayed implants may be at higher risks of implant failures and complications than delayed implants on the other hand the aesthetic outcome might be better when placing implants just after teeth extraction. There is not enough reliable evidence supporting or refuting the need for augmentation procedures at immediate implants placed in fresh extraction sockets or whether any of the augmentation techniques is superior to the others.",
        "gold": "The seven identified studies included too few patients to answer the questions. Four studies evaluated which is the best time to place implants. One study evaluated whether bone grafting is advantageous at implant placement and two studies evaluated which are the best grafting techniques. There is currently too little evidence to draw any reliable conclusions, however, the aesthetic outcome could be slightly better when placing implants early after tooth extraction, though early placed implants might be at a higher risk of failure. There is not enough evidence supporting or refusing the need of bone augmentation when extracted teeth are immediately replaced with dental implants, nor it is known whether any augmentation procedure is better than the others. Bone substitutes (anorganic bovine bone) can be used instead of self generated (autogenous) bone graft."
    },
    {
        "index": "cochrane-simplification-test-139",
        "sentence": "Two MPAC trials were identified. One trial compared clioquinol (PBT1) with placebo in 36 patients and 32 had sufficient data for per protocol analysis. There was no statistically significant difference in cognition (as measured on the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog)) between the active treatment and placebo groups at 36 weeks. The difference in mean change from baseline ADAS-Cog score in the clioquinol arm compared with the placebo arm at weeks 24 and 36 was a difference of 7.37 (95% confidence interval (CI) 1.51 to 13.24) and 6.36 (95% CI -0.50 to 13.23), respectively.There was no significant impact on non-cognitive symptoms or clinical global impression. One participant in the active treatment group developed neurological symptoms (impaired visual acuity and colour vision) which resolved on cessation of treatment and were possibly attributable to the drug. In the second trial a successor compound, PBT2, was compared with placebo in 78 participants with mild Alzheimer's dementia; all were included in the intention-to-treat analysis. There was no significant difference in the Neuropsychological Test Battery (NTB) composite or memory between placebo and PBT2 in the least squares mean change from baseline at week 12. However, two executive function component tests of the NTB showed significant improvement over placebo in the PBT2 250 mg group from baseline to week 12: category fluency test (2.8 words, 95% CI 0.1 to 5.4; P = 0.041) and trail making part B (-48.0 s, 95% CI -83.0 to -13.0; P = 0.009). In the executive factor Z score, the difference in least squares mean change from baseline at week 12 for PBT2 250 mg compared with placebo was 0\u00b727 (0\u00b701 to 0\u00b753; p=0\u00b7042).There was no significant effect on cognition on Mini-Mental State Examination (MMSE) or ADAS-Cog scales. PBT2 had a favourable safety profile. There is an absence of evidence as to whether clioquinol (PBT1) has any positive clinical benefit for patients with AD, or whether the drug is safe. We have some concerns about the quality of the study methodology; there was an imbalance in treatment and control groups after randomisation (participants in the active treatment group had a higher mean pre-morbid IQ) and the secondary analyses of results stratified by baseline dementia severity. The planned phase III trial of PBT1 has been abandoned and this compound has been withdrawn from development. The second trial of PBT2 was more rigorously conducted and showed that after 12 weeks this compound appeared to be safe and well tolerated in people with mild Alzheimer's dementia. Larger trials are now required to demonstrate cognitive efficacy.",
        "gold": "Two different types of MPAC have been used in clinical trials and the drugs are known as PBT1 and PBT2. The trial of PBT1 compared with placebo (in 36 patients) showed no statistically significant difference in cognition or memory between the active treatment and placebo groups at 36 weeks. We therefore conclude that there is no current evidence that treatment with clioquinol (PBT1) has any significant effect on cognition and in particular memory (as measured by the ADAS-Cog scale) in patients with Alzheimer's dementia. This drug has now been withdrawn from development. The trial of PBT2 showed it was safe after 12 weeks of treatment but demonstrated no overall significant effect on cognition or memory."
    },
    {
        "index": "cochrane-simplification-test-140",
        "sentence": "We included 36 studies with 2999 participants (with pulmonary hypertension from all causes) in the final review. Trials were conducted for 14 weeks on average, with some as long as 12 months. Two trials specifically included children. Nineteen trials included group 1 PAH participants. PAH participants treated with PDE5 inhibitors were more likely to improve their WHO functional class (odds ratio (OR) 8.59, 95% confidence interval (CI) 3.95 to 18.72; 4 trials, 282 participants), to walk 48 metres further in 6MWD (95% CI 40 to 56; 8 trials, 880 participants), and were 22% less likely to die over a mean duration of 14 weeks (95% CI 0.07 to 0.68; 8 trials, 1119 participants) compared to placebo (high-certainty evidence). The number needed to treat to prevent one additional death was 32 participants. There was an increased risk of adverse events with PDE5 inhibitors, especially headache (OR 1.97, 95% CI 1.33 to 2.92; 5 trials, 848 participants), gastrointestinal upset (OR 1.63, 95% CI 1.07 to 2.48; 5 trials, 848 participants), flushing (OR 4.12, 95% CI 1.83 to 9.26; 3 trials, 748 participants), and muscle aches and joint pains (OR 2.52, 95% CI 1.59 to 3.99; 4 trials, 792 participants). Data comparing PDE5 inhibitors to placebo whilst on other PAH-specific therapy were limited by the small number of included trials. Those PAH participants on PDE5 inhibitors plus combination therapy walked 19.66 metres further in six minutes (95% CI 9 to 30; 4 trials, 509 participants) compared to placebo (moderate-certainty evidence). There were limited trials comparing PDE5 inhibitors directly with other PAH-specific therapy (endothelin receptor antagonists (ERAs)). Those on PDE5 inhibitors walked 49 metres further than on ERAs (95% CI 4 to 95; 2 trials, 36 participants) (low-certainty evidence). There was no evidence of a difference in WHO functional class or mortality across both treatments. Five trials compared PDE5 inhibitors to placebo in PH secondary to left-heart disease (PH-LHD). The quality of data were low due to imprecision and inconsistency across trials. In those with PH-LHD there were reduced odds of an improvement in WHO functional class using PDE5 inhibitors compared to placebo (OR 0.53, 95% CI 0.32 to 0.87; 3 trials, 285 participants), and those using PDE5 inhibitors walked 34 metres further compared to placebo (95% CI 23 to 46; 3 trials, 284 participants). There was no evidence of a difference in mortality. Five trials compared PDE5 inhibitors to placebo in PH secondary to lung disease/hypoxia, mostly in COPD. Data were of low quality due to imprecision of effect and inconsistency across trials. There was a small improvement of 27 metres in 6MWD using PDE5 inhibitors compared to placebo in those with PH due to lung disease. There was no evidence of worsening hypoxia using PDE5 inhibitors, although data were limited. Three studies compared PDE5 inhibitors to placebo or other PAH-specific therapy in chronic thromboembolic disease. There was no significant difference in any outcomes. Data quality was low due to imprecision of effect and heterogeneity across trials. PDE5 inhibitors appear to have clear beneficial effects in group 1 PAH. Sildenafil, tadalafil and vardenafil are all efficacious in this clinical setting, and clinicians should consider the side-effect profile for each individual when choosing which PDE5 inhibitor to prescribe. While there appears to be some benefit for the use of PDE5 inhibitors in PH-left-heart disease, it is not clear based on the mostly small, short-term studies, which type of left-heart disease stands to benefit. These data suggest possible harm in valvular heart disease. There is no clear benefit for PDE5 inhibitors in pulmonary hypertension secondary to lung disease or chronic thromboembolic disease. Further research is required into the mechanisms of pulmonary hypertension secondary to left-heart disease, and cautious consideration of which subset of these patients may benefit from PDE5 inhibitors. Future trials in PH-LHD should be sufficiently powered, with long-term follow-up, and should include invasive haemodynamic data, WHO functional class, six-minute walk distance, and clinical worsening.",
        "gold": "We included 36 studies with 2999 people. Trials were conducted for 14 weeks on average, with some as long as 12 months. Most trials involved adults, and two trials specifically included children. Nineteen trials included those with group 1 pulmonary arterial hypertension (inherited, unknown, due to connective tissue diseases). People who were given PDE5 inhibitors were compared with those not given PDE5 inhibitors. This review shows that when given PDE5 inhibitors, on average people walked 48 meters further in six minutes (8 trials, 880 people). They also improved their functional class (reducing the physical limitations associated with PH), and were less likely to die (high-certainty evidence). They were also more likely to have side effects, including headache, flushing and muscle aches. Five trials included people with pulmonary hypertension due to left-heart disease. This review shows that when given PDE5 inhibitors, these people were on average able to walk 34 metres further in six minutes (3 trials, 284 people; low-certainty evidence). However, there was no difference in survival, compared to those who were not given PDE5 inhibitors. Five trials included people with pulmonary hypertension due to lung disease (mostly chronic obstructive pulmonary disease and some idiopathic pulmonary fibrosis). When given PDE5 inhibitors, they were able to walk 27 meters further in six minutes (low-certainty evidence), but with no difference in survival, compared to those who were not given PDE5 inhibitors. Three trials included people with pulmonary hypertension due to blood clots; there was no significant difference in outcomes for those who used PDE5 inhibitors compared to those who did not. There was good-quality evidence for those with pulmonary arterial hypertension, giving us some confidence that the results are correct. The evidence for those with pulmonary hypertension due to heart disease was less certain. The quality of evidence in this group was low because there were few trials, small numbers of people taking part, and the trials were quite different from each other, making it difficult to draw firm conclusions."
    },
    {
        "index": "cochrane-simplification-test-141",
        "sentence": "We included one new trial involving 45 participants in this updated review. In total we included 22 trials involving a total of 2193 participants who received regional anaesthesia for hand, wrist, forearm or elbow surgery. 'Risk of bias' assessment indicated that trial design and conduct were generally adequate; the most common areas of weakness were in blinding and allocation concealment. Nine trials comparing double versus single injections showed a statistically significant decrease in primary anaesthesia failure (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.34 to 0.89, high-quality evidence). Subgroup analysis by method of nerve location showed that the effect size was greater when neurostimulation was used rather than the transarterial technique. Nine trials comparing multiple with single injections showed a statistically significant decrease in primary anaesthesia failure (RR 0.25, 95% CI 0.14 to 0.42, high-quality evidence). Pooled data from five trials also showed a significant decrease in incomplete motor block (RR 0.61, 95% CI 0.39 to 0.96, high-quality evidence) in the multiple-injection group. Twelve trials comparing multiple versus double injections showed a statistically significant decrease in primary anaesthesia failure (RR 0.27, 95% CI 0.19 to 0.39, high-quality evidence). Pooled data from six trials also showed a significant decrease in incomplete motor block (RR 0.55, 95% CI 0.36 to 0.85, high-quality evidence) in the multiple injection group. Tourniquet pain was significantly reduced with multiple injections compared with double injections (RR 0.53, 95% CI 0.33 to 0.84, high-quality evidence). Otherwise there were no statistically significant differences between groups in any of the three comparisons on secondary analgesia failure, complications and patient discomfort. Compared with multiple injections, the time for block performance was significantly shorter for single injection (MD 3.33 minutes, 95% CI 2.76 to 3.90) and double injections (MD 1.54 minutes, 95% CI 0.80 to 2.29); however there was no difference in time to readiness for surgery. This review provides evidence that multiple-injection techniques using nerve stimulation for axillary plexus block produce more effective anaesthesia than either double or single-injection techniques. However, there was insufficient evidence to draw any definitive conclusions regarding differences in other outcomes, including safety.",
        "gold": "We searched the literature up until April 2016 and identified 22 randomized controlled trials for inclusion in the review. These trials involved a total of 2193 participants who were given regional anaesthesia for hand, wrist, forearm or elbow surgery. The trials used methods that were generally adequate and did not affect the validity of the findings. Nine trials compared double versus single injections. These found that people in the double-injection group had a 45% reduction in their chance of needing additional anaesthesia. The effect was more certain in the four trials where the nerves were located using the more precise method of neurostimulation. In the nine trials comparing multiple with single injections, and the 12 trials comparing multiple with double injections, there were significant reductions in the chance of needing additional anaesthesia in the multiple-injection groups (75% and 73% reductions when compared to single and double injections respectively). In addition, people in the multiple-injection group were 47% less likely to experience pain from the surgical tourniquet compared to the double-injection group. There were no other statistically significant differences in complications or patient discomfort between the two groups for any of the three comparisons. Single and double injections took less time to perform than multiple injections, but this did not reduce the total time required for adequate surgical anaesthesia to be established. Overall, there is high-quality evidence showing that multiple injections of anaesthetic close to three or four nerves in the armpit provide more complete anaesthesia for hand and forearm surgery than one or two injections. There was, however, not enough evidence to determine if there was a significant difference in the other outcomes, including safety."
    },
    {
        "index": "cochrane-simplification-test-142",
        "sentence": "One hundred and fifty-nine citations were identified by the search strategy and bibliography review. Three studies met the inclusion criteria. All used beclomethasone 200 mcg twice daily delivered by dry powder Diskhaler to treat children with mild-moderate asthma. Study duration was 7-12 months. In all three studies, a significant decrease in linear growth occurred in children treated with beclomethasone compared to those receiving placebo or non-steroidal asthma therapy. The average decrease, calculated through meta-analysis, was -1.54 cm per year (95% CI -1.15, -1.94). In children with mild-moderate asthma, beclomethasone 200 mcg twice daily caused a decrease in linear growth of -1.54 cm per year. These studies lasted a maximum of 54 weeks, so it remains unclear whether the decrease in growth is sustained or whether it reverses with 'catch up' after therapy is discontinued. We are unable to comment on growth effects of other inhaled steroids that have potentially less systemic effects. If inhaled steroids are required to control a child's asthma, we recommend using the minimum dose that effectively controls the child's asthma and closely following growth.",
        "gold": "The review of trials found that the inhaled steroid, beclomethasone causes an average decrease in growth of about one and a half centimetres a year. However, it is not known whether there is any catch-up growth once the treatment is stopped. More research is needed."
    },
    {
        "index": "cochrane-simplification-test-143",
        "sentence": "Three trials (139 patients) were included. APD did not differ from CAPD with respect to mortality (RR 1.49, 95% CI 0.51 to 4.37), risk of peritonitis (RR 0.75, 95% CI 0.50 to 1.11), switching from original PD modality to a different dialysis modality (RR 0.50, 95% CI 0.25 to 1.02), hernias (RR 1.26, 95% interval 0.32 to 5.01), PD fluid leaks (RR 1.06, 95% CI 0.11 to 9.83), PD catheter removal (RR 0.64, 95% CI 0.27 to 1.48) or hospital admissions (RR 0.96, 95% CI 0.43 to 2.17). There was no difference between either PD modality with respect to residual renal function (MD -0.17, 95% CI -1.66 to 1.32). One study found that peritonitis rates and hospitalisation were significantly less in patients on APD when results were expressed as episodes/patient-year. Another study found that patients on APD had significantly more time for work, family and social activities. APD has not been shown to have significant advantages over CAPD in terms of important clinical outcomes. APD may however be considered advantageous in select group of patients such as in the younger PD population and those in employment or education due to its psychosocial advantages. There is a need for a RCT comparing CAPD with APD with sufficiently large patient numbers looking at important clinical outcomes including residual renal function, accompanied by an economic evaluation to clarify the relative clinical and cost-effectiveness of both modalities.",
        "gold": "The aim of this review was to compare the effectiveness of CAPD and APD. Only three small randomised controlled trials (RCTs) (139 patients) were identified after an extensive literature search, and we found no difference between CAPD and APD for clinically important outcomes. APD may however be considered advantageous in select group of patients such as in the younger PD population and those in employment or education due to its psychosocial advantages. These outcomes were only reported in one trial. Large, long-term RCTs are needed in this area."
    },
    {
        "index": "cochrane-simplification-test-144",
        "sentence": "37 trials (9312 patients) were analysed: 15 (3343) for RT vs. CRT, 16 (2861) for CT vs. CRT, 3 (415) for RT vs. CT and 10 (3221) for IF-RT vs. EF-RT.  CRT was superior to RT in terms of OS (OR=0.76, 95% CI 0.66 to 0.89, P = 0.0004), PFS (OR=0.49, 95% CI 0.43 to 0.56, P < 0.0001) and SM (OR = 0.78, 95% CI 0.62 to 0.98, P = 0.03). The superiority of CRT also applied to early and advanced stages (mainly IIIA) separately. Excess SM with RT is due mainly to ST and is apparently caused by greater need for salvage therapy after RT.  CRT was superior to CT in terms of PFS (OR = 77, 95 % CI 0.68 to 0.77, P < 0.0001). OS was better with CRT for early stages only (OR=0.62, 95% CI 0.44 to 0.88, P = 0.006). SM risk was higher with CRT (OR = 1.38, 95% CI 1.00 to 1.89, P = 0.05), although not significant for early stages alone. This effect, also seen in AL and ST separately, was due directly to first-line treatment.  Data were insufficient to compare RT to CT.  EF-RT was superior to IF-RT (each additional to CT in most trials) in terms of PFS (OR=81, 95% CI 0.68 to 0.95, P = 0.009) but not OS. No significant difference in SM was observed. CRT seems to be optimal for most early stage (I-II) HD patients. For advanced stages (III to IV), CRT better prevents progression/relapse but CT alone seems to cause less SM.  RT alone gives a higher overall SM risk than CRT due to increased need for salvage therapy. Reduced SM risk after IF-RT instead of EF-RT could not be demonstrated. Due to the large number of studies excluded because no IPD were received, to the inclusion of many outdated treatments and to the limited amount of long-term data, one must be cautious in applying these results to current therapies.",
        "gold": "A meta-analysis of data from 37 randomised trials including over 9000 patients was conducted. For early-stage patients, CRT resulted in longer survival and longer HD-free survival than either RT or CT alone. Second malignancy (SM) risk was lower with CRT than with RT (no difference in between CRT and CT was demonstrated). For advanced stages, no difference in survival between CRT and CT was established. With CRT, HD-free survival was longer but SM risk was higher."
    },
    {
        "index": "cochrane-simplification-test-145",
        "sentence": "We reviewed 26 studies with 27 treatment groups that enrolled a total of 4893 participants. Twenty five of the studies were case series or uncontrolled long-term trial continuations, the other was an RCT comparing two opioids. Opioids were administered orally (number of study treatments groups [abbreviated as \"k\"] = 12, n = 3040), transdermally (k = 5, n = 1628), or intrathecally (k = 10, n = 231). Many participants discontinued due to adverse effects (oral: 22.9% [95% confidence interval (CI): 15.3% to 32.8%]; transdermal: 12.1% [95% CI: 4.9% to 27.0%]; intrathecal: 8.9% [95% CI: 4.0% to 26.1%]); or insufficient pain relief (oral: 10.3% [95% CI: 7.6% to 13.9%]; intrathecal: 7.6% [95% CI: 3.7% to 14.8%]; transdermal: 5.8% [95% CI: 4.2% to 7.9%]). Signs of opioid addiction were reported in 0.27% of participants in the studies that reported that outcome. All three modes of administration were associated with clinically significant reductions in pain, but the amount of pain relief varied among studies. Findings regarding quality of life and functional status were inconclusive due to an insufficient quantity of evidence for oral administration studies and inconclusive statistical findings for transdermal and intrathecal administration studies. Many patients discontinue long-term opioid therapy (especially oral opioids) due to adverse events or insufficient pain relief; however, weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief. Whether quality of life or functioning improves is inconclusive. Many minor adverse events (like nausea and headache) occurred, but serious adverse events, including iatrogenic opioid addiction, were rare.",
        "gold": "The findings of this systematic review suggest that proper management of a type of strong painkiller (opioids) in well-selected patients with no history of substance addiction or abuse can lead to long-term pain relief for some patients with a very small (though not zero) risk of developing addiction, abuse, or other serious side effects. However, the evidence supporting these conclusions is weak, and longer-term studies are needed to identify the patients who are most likely to benefit from treatment."
    },
    {
        "index": "cochrane-simplification-test-146",
        "sentence": "The review contains only one trial with a total of 212 participants, all with spinal cord injury and open pressure ulcers classed as stage III and IV. The participants were mainly male (98.2%, 106/108) with a mean age of 58.4 (standard deviation 10.4) years in the oxandrolone group and were all male (100%, 104/104) with a mean age of 57.3 (standard deviation 11.6) years in the placebo group. This trial compared oxandrolone (20 mg/day, administered orally) with a dose of placebo (an inactive substance consisting of 98% starch and 2% magnesium stearate) and reported data on complete healing of ulcers and adverse events. There was very low-certainty evidence on the relative effect of oxandrolone on complete ulcer healing at the end of a 24-week treatment period (risk ratio RR) 0.81, 95% confidence interval (CI) 0.52 to 1.26) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, we are uncertain whether oxandrolone improves or reduces the complete healing of pressure ulcers, as we assessed the certainty of the evidence as very low. There was low-certainty evidence on the risk of non-serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 3.85, 95% CI 1.12 to 13.26) (downgraded once for imprecision and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, the treatment with oxandrolone may increase the risk of non-serious adverse events reported in participants. There was very low-certainty evidence on the risk of serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 0.54, 95% CI 0.25 to 1.17) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Of the five serious adverse events reported in the oxandrolone-treated group, none were classed by the trial teams as being related to treatment. We are uncertain whether oxandrolone increases or decreases the risk of serious adverse events as we assessed the certainty of the evidence as very low. Secondary outcomes such as pain, length of hospital stay, change in wound size or wound surface area, incidence of different type of infection, cost of treatment and quality of life were not reported in the included trial. Overall the evidence in this study was of very low quality (downgraded for imprecision and indirectness). This trial stopped early when the futility analysis (interim analysis) in the opinion of the study authors showed that oxandrolone had no benefit over placebo for improving ulcer healing. There is no high quality evidence to support the use of anabolic steroids in treating pressure ulcers. Further well-designed, multicenter trials, at low risk of bias, are necessary to assess the effect of anabolic steroids on treating pressure ulcers, but careful consideration of the current trial and its early termination are required when planning future research.",
        "gold": "In March 2017, we searched for randomised controlled trials, which compared the use of anabolic steroids with other treatments for pressure ulcers. We found only one trial involving a total of 212 participants. This trial compared the effects of an anabolic steroid (oxandrolone capsules) with a placebo (dummy treatment containing no active medicine) on pressure ulcer healing in people with spinal cord injuries. The participants were mostly male (98.2%) with a mean age of 58.4 years in the oxandrolone group, which was comparable with the participants in the placebo group (male: 100%; mean age: 57.3 years). The trial was conducted over 24 weeks with a further follow-up for eight weeks. The trial was ended early as the trial authors deemed that the interim results suggested that there was unlikely to be a benefit from treatment with oxandrolone. Because of the limited data available from one trial, we remain uncertain whether anabolic steroids have beneficial effects on pressure ulcer healing, whether the treatment causes increased serious adverse events and if the treatment may increase the risk of non-serious adverse events. Overall, the evidence from this study was judged to be of very low quality. More, better-designed studies are necessary to provide evidence as to whether anabolic steroids are beneficial or not in treating pressure ulcers. This plain language summary is up to date as of March 2017."
    },
    {
        "index": "cochrane-simplification-test-147",
        "sentence": "We included six randomised controlled trials involving 8372 people. All trials were judged to be at high risk of bias for at least one domain. Four trials compared email communication to standard mail and two compared email communication to usual care. For the primary health service outcome of uptake of preventive screening, there was no difference between email and standard mail (OR 0.93; 95% CI 0.69 to 1.24). For both comparisons (email versus standard mail and email versus usual care) there was no difference between the groups for patient or caregiver understanding and support. Results were inconclusive for patient or caregiver behaviours and actions. For email versus usual care only, there was no significant difference between groups for the primary outcome of patient health status and well-being. No data were reported relating to healthcare professionals or harms. The evidence on the use of email for the provision of information on disease prevention and health promotion was weak, and therefore inadequate to inform clinical practice. The available trials mostly provide inconclusive, or no evidence for the outcomes of interest in this review. Future research needs to use high-quality study designs that take advantage of the most recent developments in information technology, with consideration of the complexity of email as an intervention.",
        "gold": "We found that there was not much evidence on the effects of using email to give people information on disease prevention and health promotion. We found only six trials with 8372 participants in total. All of the trials had elements of bias. Four studies compared email to standard mail as a method of communication, and found that using email instead of mail did not make any difference to patient or caregiver understanding, or the uptake of preventive screening. Two studies compared email with usual care, and found that using email instead of usual methods of information delivery did make any difference to patient or caregiver understanding and support, or patient health status and well-being. We were unable to properly assess email's impact on patient or caregiver behaviours/actions as the results were mixed. As there is a lack of good quality evidence for whether email can be used by healthcare professionals to provide information to patients or caregivers on how to stay healthy and avoid disease, we need to think about how to get good measurable information on this. Future studies should follow advice on good ways of carrying out and presenting research. It would be useful if they could look at the costs of using email and take into account ongoing changes in technology."
    },
    {
        "index": "cochrane-simplification-test-148",
        "sentence": "The review includes 11 trials involving 855 participants. A total of nine studies used post-Epley postural restrictions as their modification of the Epley manoeuvre. There was no evidence of a difference in the results for post-treatment vertigo intensity or subjective assessment of improvement in individual or pooled data. All nine trials included the conversion of a positive to a negative Dix-Hallpike test as an outcome measure. Pooled data identified a significant difference from the addition of postural restrictions in the frequency of Dix-Hallpike conversion when compared to the Epley manoeuvre alone. In the experimental group 88.7% (220 out of 248) patients versus 78.2% (219 out of 280) in the control group converted from a positive to negative Dix-Hallpike test (risk ratio (RR) 1.13, 95% confidence interval (CI) 1.05 to 1.22, P = 0.002). No serious adverse effects were reported, however three studies reported minor complications such as neck stiffness, horizontal BPPV, dizziness and disequilibrium in some patients. There was no evidence of benefit of mastoid oscillation applied during the Epley manoeuvre, or of additional steps in the Epley manoeuvre. No adverse effects were reported. There is evidence supporting a statistically significant effect of post-Epley postural restrictions in comparison to the Epley manoeuvre alone. However, it important to note that this statistically significant effect only highlights a small improvement in treatment efficacy. An Epley manoeuvre alone is effective in just under 80% of patients with typical BPPV. The additional intervention of postural restrictions has a number needed to treat (NNT) of 10. The addition of postural restrictions does not expose the majority of patients to risk of harm, does not pose a major inconvenience, and can be routinely discussed and advised. Specific patients who experience discomfort due to wearing a cervical collar and inconvenience in sleeping upright may be treated with the Epley manoeuvre alone and still expect to be cured in most instances. There is insufficient evidence to support the routine application of mastoid oscillation during the Epley manoeuvre, or additional steps in an 'augmented' Epley manoeuvre. Neither treatment is associated with adverse outcomes. Further studies should employ a rigorous randomisation technique, blinded outcome assessment, a post-treatment Dix-Hallpike test as an outcome measure and longer-term follow-up of patients.",
        "gold": "We included 11 studies in this review, with a total of 855 participants. Nine studies looked at post-treatment postural restrictions (using a neck brace/head movement restrictions/instructions to sleep upright) following the Epley manoeuvre. There was a statistically significant difference found when these restrictions were compared to a control treatment of the Epley manoeuvre alone. Although there was a difference between the groups, adding postural restrictions conferred only a small additional benefit since the Epley manoeuvre was effective alone in just under 80% of patients. Four of the studies reported minor complications such as neck stiffness, horizontal BPPV (a subtype of BPPV which is similar to posterior canal BPPV, but has some distinct differences in terms of the signs and symptoms), dizziness and disequilibrium (the feeling of unsteadiness on ones feet) in some patients. Additionally, two studies looked into the application of oscillation/vibration to the mastoid region during the Epley manoeuvre compared to control; the intervention produced no difference in outcome between these groups. One study that also researched post-treatment postural restrictions looked into extra steps in the Epley manoeuvre. Compared to the control treatment there were no significant differences in outcomes. No serious adverse effects were reported in any of the studies in the review. The results should be interpreted carefully and further trials are needed."
    },
    {
        "index": "cochrane-simplification-test-149",
        "sentence": "Four studies (231 participants randomised) are included in the review. No studies were at low risk of bias. The studies compared different types of surgery versus various types and doses of systemic and topical steroids and antibiotics. There were three comparison pairs: (1) endoscopic sinus surgery (ESS) versus systemic steroids (one study, n = 109), (2) polypectomy versus systemic steroids (two studies, n = 87); (3) ESS plus topical steroid versus antibiotics plus high-dose topical steroid (one study, n = 35). All participants also received topical steroids but doses and types were the same between the treatment arms of each study, except for the study using antibiotics. In that study, the medical treatment arm had higher doses than the surgical arm. In two of the studies, the authors failed to report the outcomes of interest. Although there were important differences in the types of treatments and comparisons used in these studies, the results were similar. Primary outcomes: symptom scores and quality of life scores There were no important differences between groups in either the patient-reported disease-specific symptom scores or the health-related quality of life scores. Two studies (one comparing ESS plus topical steroid versus antibiotics plus high-dose topical steroid, the other ESS versus systemic steroids) failed to find a difference in generic health-related quality of life scores. The quality of this evidence is low or very low. Endoscopic scores and other secondary outcomes Two studies reported endoscopic scores. One study (ESS versus systemic steroids) reported a large, significant effect size in the surgical group, with a mean difference (MD) in score of -1.5 (95% confidence interval (CI) -1.78 to -1.22, n = 95) on a scale of 0 to 3 (0 = no polyposis, 3 = severe polyposis). In the other study (ESS plus topical steroid versus antibiotics plus high-dose topical steroid) no difference was found between the groups (MD 2.3%, 95% CI -17.4% to 12.8%, n = 34). None of the included studies reported recurrence rates. No differences were found for any objective measurements or olfactory tests in those studies in which they were measured. Complications Complication rates were not reported in all studies, but rates of up to 21% for medical treatment and 14.3% for surgical treatment are described. Epistaxis was the most commonly reported complication with both medical and surgical treatments, with severe complications reported rarely. The evidence relating to the effectiveness of different types of surgery versus medical treatment for adults with chronic rhinosinusitis with nasal polyps is of very low quality. The evidence does not show that one treatment is better than another in terms of patient-reported symptom scores and quality of life measurements. The one positive finding from amongst the several studies examining a number of different comparisons must be treated with appropriate caution, in particular when the clinical significance of the measure is uncertain. As the overall evidence is of very low quality (serious methodological limitations, reporting bias, indirectness and imprecision) and insufficient to draw firm conclusions, further research to investigate this problem, which has significant implications for quality of life and healthcare service usage, is justified.",
        "gold": "Four randomised controlled trials, involving a total of 231 patients with chronic rhinosinusitis with nasal polyps, are included in this review. The number of patients in each study ranged from 34 to 109. The studies took place in ENT departments in several European countries. All patients were adults and most of the studies enrolled more men than women. In all studies the patients were randomly assigned to either surgery or medical treatment (such as antibiotics or steroid tablets or injections) in addition to topical steroids given as nasal sprays or drops. Both the type of surgery performed and the medical treatments used varied widely between the studies, and did not allow all of the studies to be looked at together. Rather, we considered the treatment groups in the four studies as three separate pairs of comparisons instead of simply 'surgical' versus 'medical' treatments. The main outcome measures were patient-reported disease-specific symptom scores and health-related quality of life scores, as well as generic health-related quality of life scores. There were no important differences between groups in either the patient-reported disease-specific symptom scores or the health-related quality of life scores. Two studies (one comparing ESS plus topical steroid versus antibiotics plus high-dose topical steroid, the other ESS versus systemic steroids) did not find a difference in general health-related quality of life scores. Two studies reported changes in polyp size (when looked at with an endoscope) using a score. One study (ESS versus systemic steroids) reported a significantly better score in the surgery group than in the steroids group at 12 months. In the other study (ESS plus topical steroid versus antibiotics plus high-dose topical steroid) no difference was found between the groups. There were no reported differences between the different medical and surgical treatment groups in any study for any other objective (clinician-based) measurements. Complication rates were not reported in all studies, but nosebleeds (epistaxis) were the most commonly described complication with both medical and surgical treatment; severe complications were reported rarely in either group. The evidence does not show that one treatment is better than another in terms of patient-reported symptom scores and quality of life measurements. One positive finding (polyps size scores) from amongst the several studies examining a number of different comparisons must be treated with appropriate caution, in particular when the clinical significance of the measure is uncertain. There is not enough evidence to draw firm conclusions regarding the most appropriate treatment for this condition. Chronic rhinosinusitis with nasal polyps has significant implications for quality of life and the use of healthcare services. Further research to investigate this problem is justified. Overall, we found this evidence to be of low or very low quality. We have low confidence in the estimates of these studies; further research will very likely change these estimates. There were serious limitations in how the studies were carried out or reported (or both), and the number of participants involved was small. In addition, some of the treatment regimens used in the trials are no longer current standards of therapy for patients with chronic rhinosinusitis with nasal polyps. This evidence is up to date to 20 February 2014."
    },
    {
        "index": "cochrane-simplification-test-150",
        "sentence": "We included eight trials (709 participants); seven were from middle-income countries of Asia, Africa, Europe, and Latin America where zinc deficiency is likely to be a public health problem. Four trials compared the effect of zinc-fortified staple foods with unfortified foods (comparison 1), and four compared zinc-fortified staple foods in combination with other nutrients/factors with the same foods containing other nutrients or factors without zinc (comparison 2). The interventions lasted between one and nine months. We categorised most trials as having unclear or high risk of bias for randomisation, but low risk of bias for blinding and attrition. None of the studies in comparison 1 reported data on zinc deficiency. Foods fortified with zinc increased the serum or plasma zinc levels in comparison to foods without added zinc (mean difference (MD) 2.12 \u00b5mol/L, 95% confidence interval (CI) 1.25 to 3.00 \u00b5mol/L; 3 studies; 158 participants; low-quality evidence). Participants consuming foods fortified with zinc versus participants consuming the same food without zinc had similar risk of underweight (average risk ratio 3.10, 95% CI 0.52 to 18.38; 2 studies; 397 participants; low-quality evidence) and stunting (risk ratio (RR) 0.88, 95% CI 0.36 to 2.13; 2 studies; 397 participants; low-quality evidence). A single trial of addition of zinc to iron in wheat flour did not find a reduction in proportion of zinc deficiency (RR 0.17, 95% CI 0.01 to 3.94; very low-quality evidence). We did not find a difference in serum or plasma zinc levels in participants consuming foods fortified with zinc plus other micronutrients when compared with participants consuming the same foods with micronutrients but no added zinc (MD 0.03 \u00b5mol/L, 95% CI -0.67 to 0.72 \u00b5mol/L; 4 studies; 250 participants; low-quality evidence). No trial in comparison 2 provided information about underweight or stunting. There was no reported adverse effect of fortification of foods with zinc on indicators of iron or copper status. Fortification of foods with zinc may improve the serum zinc status of populations if zinc is the only micronutrient used for fortification. If zinc is added to food in combination with other micronutrients, it may make little or no difference to the serum zinc status. Effects of fortification of foods with zinc on other outcomes including zinc deficiency, children\u2019s growth, cognition, work capacity of adults, or on haematological indicators are unknown. Given the small number of trials and participants in each trial, further investigation of these outcomes is required.",
        "gold": "We included eight trials (709 participants); seven were from middle-income countries of Asia, Africa, Europe, and Latin America where zinc deficiency is likely to be a public health problem. The effect of fortification of foods with zinc on incidence of zinc deficiency is uncertain. Fortification of foods with zinc may slightly improve the blood zinc levels of populations if zinc is the only micronutrient used for fortification. Zinc added to food in combination with other micronutrients may make little or no difference to blood zinc levels. The fortification of foods with zinc may make little or no difference on incidence of underweight or stunting. The effects of fortification of foods with zinc on other outcomes, including wasting and weight/height, are unknown. Fortification of foods with zinc does not seem to have any adverse effect on indicators of iron or copper status. Most studies included in this review involved a small number of participants and were judged to be at low or unclear risk of bias. There were also some inconsistencies in the results across different studies."
    },
    {
        "index": "cochrane-simplification-test-151",
        "sentence": "Eleven studies involving 3060 randomly assigned participants were included in this review. The quality of evidence is hampered by risk of bias. Use of non-steroidal antiandrogens decreased overall survival (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.05 to 1.48, six studies, 2712 participants) and increased clinical progression (one year: risk ratio (RR) 1.25, 95% CI 1.08 to 1.45, five studies, 2067 participants; 70 weeks: RR 1.26, 95% CI 1.08 to 1.45, six studies, 2373 participants; two years: RR 1.14, 95% CI 1.04 to 1.25, three studies, 1336 participants), as well as treatment failure (one year: RR 1.19, 95% CI 1.02 to 1.38, four studies, 1539 participants; 70 weeks: RR 1.27, 95% CI 1.05 to 1.52, five studies, 1845 participants; two years: RR 1.14, 95% CI 1.05 to 1.24, two studies, 808 participants), compared with medical or surgical castration. The quality of evidence for overall survival, clinical progression and treatment failure was rated as moderate according to GRADE. Predefined subgroup analyses showed that use of non-steroidal antiandrogens, compared with castration, was less favourable for overall survival, clinical progression (at one year, 70 weeks, two years) and treatment failure (at one year, 70 weeks, two years) in men with metastatic disease. Use of non-steroidal antiandrogens also increased the risk for treatment discontinuation due to adverse events (RR 1.82, 95% CI 1.13 to 2.94, eight studies, 1559 participants), including events such as breast pain (RR 22.97, 95% CI 14.79 to 35.67, eight studies, 2670 participants), gynaecomastia (RR 8.43, 95% CI 3.19 to 22.28, nine studies, 2774 participants) and asthenia (RR 1.77, 95% CI 1.36 to 2.31, five studies, 2073 participants). The risk of other adverse events, such as hot flashes (RR 0.23, 95% CI 0.19 to 0.27, nine studies, 2774 participants), haemorrhage (RR 0.07, 95% CI 0.01 to 0.54, two studies, 546 participants), nocturia (RR 0.38, 95% CI 0.20 to 0.69, one study, 480 participants), fatigue (RR 0.52, 95% CI 0.31 to 0.88, one study, 51 participants), loss of sexual interest (RR 0.50, 95% CI 0.30 to 0.83, one study, 51 participants) and urinary frequency (RR 0.22, 95% CI 0.11 to 0.47, one study, 480 participants) was decreased when non-steroidal antiandrogens were used. The quality of evidence for breast pain, gynaecomastia and hot flashes was rated as moderate according to GRADE. The effects of non-steroidal antiandrogens on cancer-specific survival and biochemical progression remained unclear. Currently available evidence suggests that use of non-steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation due to adverse events. Evidence quality was rated as moderate according to GRADE. Further research is likely to have an important impact on results for patients with advanced but non-metastatic prostate cancer treated with non-steroidal antiandrogen monotherapy. However, we believe that research is likely not necessary on non-steroidal antiandrogen monotherapy for men with metastatic prostate cancer. Only high-quality, randomised controlled trials with long-term follow-up should be conducted. If further research is planned to investigate biochemical progression, studies with standardised follow-up schedules using measurements of prostate-specific antigen based on current guidelines should be conducted.",
        "gold": "The evidence is current to December 2013. We included 11 studies involving 3060 randomly assigned participants at advanced stages of prostate cancer. The follow-up period of participants ranged from six months to six years. In seven studies, authors reported possible conflicts of interest. In three studies, no conflicts of interest were declared. In one study, authors reported that they had received an educational grant from the sponsor, who had no role in any aspect of analysis or data interpretation. Use of non-steroidal antiandrogens decreased overall survival and increased clinical progression and treatment failure. Subgroup analyses showed that non-steroidal antiandrogens, compared with castration, were less favourable for overall survival, for clinical progression and for treatment failure in men with metastatic disease. Participants receiving antiandrogens were also more likely to stop treatment as the result of side effects. The risk of suffering breast pain, enlargement of breast tissue or symptoms of physical weakness was also increased with non-steroidal antiandrogens. The risks of feeling intense heat with sweating and rapid heartbeat and of bleeding, the need to get up in the night to urinate, loss of sexual interest, extreme tiredness and the need to urinate more often than usual were increased with castration. No difference was noted for other side effects. The effect of non-steroidal antiandrogens on cancer-specific survival and biochemical progression remained unclear. Included studies were poorly conducted, and the quality of evidence was rated as moderate. This means that further research is likely to have an important impact on our confidence in the accuracy of results."
    },
    {
        "index": "cochrane-simplification-test-152",
        "sentence": "Eight eligible trials were identified. We excluded a trial because the randomisation had failed to produce comparable groups.The eligible trials included 600,000 women in the analyses in the age range 39 to 74 years. Three trials with adequate randomisation did not show a statistically significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomisation showed a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87).  We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on total cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03). Total numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR 1.31, 95% CI 1.22 to 1.42), as were number of mastectomies (RR 1.20, 95% CI 1.08 to 1.32). The use of radiotherapy was similarly increased whereas there was no difference in the use of chemotherapy (data available in only two trials). If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings. To help ensure that the women are fully informed before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening.",
        "gold": "Screening with mammography uses X-ray imaging to find breast cancer before a lump can be felt. The goal is to treat cancer earlier, when a cure is more likely. The review includes seven trials that involved 600,000 women in the age range 39 to 74 years who were randomly assigned to receive screening mammograms or not. The studies which provided the most reliable information showed that screening did not reduce breast cancer mortality. Studies that were potentially more biased (less carefully done) found that screening reduced breast cancer mortality. However, screening will result in some women getting a cancer diagnosis even though their cancer would not have led to death or sickness. Currently, it is not possible to tell which women these are, and they are therefore likely to have breasts or lumps removed and to receive radiotherapy unnecessarily. If we assume that screening reduces breast cancer mortality by 15% after 13 years of follow-up and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings. Women invited to screening should be fully informed of both the benefits and harms. To help ensure that the requirements for informed choice for women contemplating whether or not to attend a screening programme can be met, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening."
    },
    {
        "index": "cochrane-simplification-test-153",
        "sentence": "We included four studies, with a total of 522 women, in the review. One of these studies did not report outcomes per woman randomised, and so was not included in formal analysis. Three studies investigated 10,000 units hCG priming compared to no priming. One study investigated 20,000 units hCG compared to 10,000 units hCG priming. Three studies only included women with PCOS (N = 122), while this was an exclusion criteria in the fourth study (N = 400). We rated all four studies as having an unclear risk of bias in more than one of the seven domains assessed. The quality of the evidence was low, the main limitations being lack of blinding and imprecision. When 10,000 units hCG priming was compared to no priming, we found no evidence of a difference in the live birth rates per woman randomised (OR 0.65, 95% confidence intervals (CI) 0.24 to 1.74; one RCT; N = 82; low quality evidence); miscarriage rate (OR 0.60, 95% CI 0.21 to 1.72; two RCTs; N = 282; I\u00b2 statistic = 21%; low quality evidence), or clinical pregnancy rate (OR 0.52, 95% CI 0.26 to 1.03; two RCTs, N = 282, I\u00b2 statistic = 0%, low quality evidence). Though inconclusive, our findings suggested that hCG may be associated with a reduction in clinical pregnancy rates; 22% of women who received no priming achieved pregnancy, while between 7% and 23% of women who received hCG priming did so. The study comparing 20,000 units hCG with 10,000 units hCG did not report sufficient data to enable us to calculate odds ratios. No studies reported on adverse events (other than miscarriage) or drug reactions. This review found no conclusive evidence that hCG priming had an effect on live birth, pregnancy, or miscarriage rates in IVM. There was low quality evidence that suggested that hCG priming may reduce clinical pregnancy rates, however, these findings were limited by the small number of data included. As no data were available on adverse events (other than miscarriage) or on drug reactions, we could not adequately assess the safety of hCG priming. We need further evidence from well-designed RCTs before we can come to definitive conclusions about the role of hCG priming, and the optimal dose and timing.",
        "gold": "This review included four randomised controlled trials, with a total of 522 women. One study investigated the use of 20,000 units hCG priming compared to 10,000 units. The remaining studies investigated 10,000 units hCG priming compared to no priming. The main outcomes were live birth rate and miscarriage rate per woman randomised. Evidence published up to 29 August 2016 was examined. Only one study reported the main outcome of live birth per woman randomised; two studies reported clinical pregnancy. We found no certain evidence of a difference between 10,000 units hCG priming and no priming. However, there was some low quality evidence to suggest that hCG may be associated with a reduction in pregnancy rates; 22% of women who received no priming achieved pregnancy, while between 7% and 23% of women who received hCG priming did so. Two studies reported miscarriage rate per woman randomised, and found no evidence of a difference between 10,000 units hCG priming and no priming. No studies reported on adverse events (other than miscarriage) or drug reactions. Overall, there was insufficient evidence to draw any definite conclusions on the use of hCG priming in IVM. Further randomised trials are necessary, in particular, focusing on women with PCOS. The quality of the evidence was low, the main limitations being imprecision (random error) and lack of blinding (the process in which participant and assessor are prevented from knowing which intervention has been received)."
    },
    {
        "index": "cochrane-simplification-test-154",
        "sentence": "In total, 24 trials were included, but only 16 (10,114 women) had analysable data. Meta-analyses showed no effects of either ERT or HRT on prevention of cognitive impairment after five and four years of treatment, respectively (odds ratio 1.34, 95% CI 0.95 to 1.9; odds ratio 1.05, 95% CI 0.72 to 1.54 respectively) (trend favouring control in both instances). Analyses assessing the effects of treatment over time found that both ERT and HRT did not maintain or improve cognitive function and may even adversely affect this outcome (WMD = -0.45, 95% CI -0.99 to 0.09; WMD = -0.16, 95% CI -0.58 to 0.26, respectively at maximum follow up). Negative effects were found for ERT after one year and HRT after three and four years of therapy. Results from smaller trials assessing effects on individual cognitive domains mostly reported no evidence of benefit. There is good evidence that both ERT and HRT do not prevent cognitive decline in older postmenopausal women when given as short term or longer term (up to five years) therapy. It is not known whether either specific types of ERT or HRT have specific effects in subgroups of women, although there was evidence that combined hormone therapy in similarly aged women was associated with a decrement in a number of verbal memory tests and a small improvement in a test of figural memory. There is insufficient evidence to determine whether subgroups of women using specific types of hormone therapy could benefit from treatment. It remains to be determined whether factors such as younger age (< 60 years of age), type of menopause (surgical or natural) and type of treatment (type of estrogen with or without a progestagen), mode of delivery (transdermal, oral or intramuscular) and dosage have positive effects at a clinically relevant level. In addition, whether the absence or presence of menopausal symptoms can modify treatment effects should be investigated in more detail. Large RCTs currently underway in the USA may be able to provide answers to these uncertainties by the year 2010. In the meantime, based on the available evidence, ERT or HRT cannot be recommended for overall cognitive improvement or maintenance in older postmenopausal women without cognitive impairment.",
        "gold": "Animal studies (performed both in the laboratory and on living animals) suggest that estrogen alone might protect the brain as women get older. After the menopause, levels of estrogens decline in women and estrogen therapy has been claimed to maintain or enhance cognitive function in postmenopausal women. This review found no evidence of a benefit of any types of estrogen on overall cognitive functioning in older postmenopausal women when given either as short term or longer term (up to five years) therapy. There was also no evidence of a beneficial effect of combined estrogen and progestagen therapy overall. There was insufficient evidence to determine whether any type of hormone replacement therapy had beneficial or harmful effects on specific types of cognitive ability, such as verbal or visual memory."
    },
    {
        "index": "cochrane-simplification-test-155",
        "sentence": "We included two studies with 880 participants. We identified one ongoing trial with planned recruitment of 80 participants. Included studies enrolled participants with both partially reversible and non-reversible COPD and baseline mean per cent predicted (%pred) forced expiratory volume in one second (FEV\u2081) of 43.4 to 49.6. Both studies lasted 12 weeks. Both studies used the same combination of inhaled ICS/LABA (fluticasone furoate and vilanterol 100/25 mcg once daily; FF/VI) versus LAMA (18 mcg tiotropium; TIO). They were published as full articles, and neither study was at low risk of bias in all domains. Compared to the TIO arm, results for pooled primary outcomes for the FF/VI arm were as follows: mortality: OR 0.20, 95% CI 0.02 to 1.73, 880 participants (deaths reported only in the TIO arm), very low-quality evidence; COPD exacerbation (requiring short-burst oral corticosteroids or antibiotics, or both): OR 0.72, 95% Cl 0.35 to 1.50, 880 participants, very low-quality evidence; pneumonia: reported in both studies only during treatment with FF/VI: OR 6.12, 95% Cl 0.73 to 51.24, 880 participants, very low-quality evidence; and total serious adverse events: OR 0.96, 95% Cl 0.50 to 1.83, 880 participants, very low-quality evidence. None of the pneumonias were fatal. Compared to the TIO arm, we found no statistically significant difference for pooled secondary outcomes, including St George's Respiratory Questionnaire (SGRQ) mean total score change; hospital admissions (all-cause); disease-specific adverse events; mean weekly rescue medication use (results available from only one of the studies); and mean weekly percentage of rescue-free days for FF/VI. We found no statistically significant differences between ICS/LABA and LAMA for improvement in symptoms measured by the COPD Assessment Test (CAT score) nor for FEV\u2081 (change from baseline trough in 24-hour weighted mean on treatment day 84). Many pooled estimates lacked precision. Data for other endpoints such as exacerbations leading to intubation and physical activity measures were not available in included trials. Based on analysis of primary and secondary outcomes, we are uncertain whether once-daily ICS/LABA, combined in one inhaler, has a different efficacy or adverse effect profile compared to LAMA for treatment of people with COPD. However, the current review is based on only two trials with the main focus on primary outcomes other than those considered in this review. The short follow-up period and the very low quality of evidence limit our confidence in the result and increase uncertainty. Further trials of longer duration are needed. Current evidence is not strong enough to demonstrate important differences between inhalers in terms of effects, nor to establish that once-daily fluticasone/vilanterol 100/25 mcg and tiotropium 18 mcg are equivalent.",
        "gold": "We found two studies involving 880 participants that compared the benefits and harms of once-daily inhaled ICS/LABA combined in one inhaler versus inhaled LAMA for treatment of adults with COPD. These studies lasted 12 weeks. Participants were men and women aged 40 or older who had COPD with various degrees of severity. No consistent differences were found between the two different types of inhalers included in this review. Researchers reported no major differences in death rate, numbers of COPD exacerbations, lung inflammation, or other serious unwanted events.  People receiving both inhalers showed similar improvements in quality of life, symptoms, and lung function tests. Overall, we assessed the evidence presented in this review to be of very low quality, which means we have very little confidence in the findings. The main reasons for such judgement include the small number of identified studies and the fact that these studies were not focused on the outcomes of interest for this review. Also, both studies had a short observation time, which means that most of the undesired events may have occurred after the observation period was over. From this review, we did not find evidence strong enough to demonstrate major differences between inhalers or to establish that these inhalers have the same effect."
    },
    {
        "index": "cochrane-simplification-test-156",
        "sentence": "Two pharmacotherapy and three psychotherapy trials were eligible for inclusion in the review, with data from four short-term RCTs (169 participants) available for analysis. Response data from a single placebo-controlled trial of fluoxetine suggested overall superiority of medication relative to placebo (relative risk (RR) 3.07, 95% CI 1.4 to 6.72, n = 67). Symptom severity was also significantly reduced in the RCTs of fluoxetine and clomipramine (relative to desipramine), as well as in the two CBT trials (WMD -44.96, 95% CI -54.43 to -35.49, n = 73). A low relapse rate (4/22) was demonstrated in one trial of CBT. Results from the small number of available RCTs suggest that SRIs and CBT may be useful in treating patients with BDD. The findings of these studies need to be replicated. In addition, future controlled studies in other samples, such as adolescents, and using other selective SRIs, as well as a range of psychological therapy approaches and modalities (alone and in combination), are essential in supplementing the sparse data currently available.",
        "gold": "Our systematic review of randomised controlled trials assesses the effects of drug treatment or psychotherapy when used on their own or in combination. We found five eligible trials, including three of psychotherapy (cognitive behavioural therapy (CBT) and exposure and response prevention (ERP)) and two of medication (the serotonin reuptake inhibitors (SRIs) fluoxetine and clomipramine). In the only placebo-controlled medication trial included in our review, people with BDD treated with fluoxetine were more likely to respond (56%, 19 out of 34) than those allocated placebo (18%, 6 out of 33). Symptoms became less severe after treatment with both medication and psychotherapy. Adverse events were mild to moderate in severity and none of the people in the active treatment groups were reported to have dropped out of the studies because of treatment-emergent adverse events. There is preliminary evidence from one trial of CBT that the effects of CBT may persist once treatment has ended. Treatment response in the medication trials was not effected by the degree to which people had insight into their condition. Although few controlled trials have been done, and those that have been conducted were small, indicating that our findings should be used with caution unless confirmed by larger studies (some of which are ongoing), the results suggest that treatment with both medication or psychotherapy can be effective in treating the symptoms of body dysmorphic disorder."
    },
    {
        "index": "cochrane-simplification-test-157",
        "sentence": "Three trials that examined cotrimoxazole prophylaxis and involving 268 adults were included. Meta-analysis of these studies found a beneficial effect of using a desensitization protocol over a rechallenge protocol at six months of follow-up for preventing discontinuation of cotrimoxazole (number needed to treat (NNT) 7.14, 95% confidence interval (CI) 4.0-33.0), and for lower incidence of overall hypersensitivity (NNT 4.55, 95% CI 3.03-9.09). No severe hypersensitivity reactions occurred for either protocol in the three studies. In the small trials included in this review, when compared to cotrimoxazole rechallenge for prophylaxis of opportunistic infections, cotrimoxazole desensitization resulted in fewer treatment discontinuations and overall adverse reactions in HIV-infected patients with a previous history of mild or moderate hypersensitivity to cotrimoxazole. Paediatric data and trials in resource-poor settings are urgently required. Further randomised controlled trials are also needed for the treatment of opportunistic infections, treating-through, adjunctive medications, and different desensitization-dosing schedules.",
        "gold": "Three trials examining the use of cotrimoxazole in preventing opportunistic infections were included in the review. When compared to rechallenge, desensitization appeared to result in fewer treatment stoppages and side effects in HIV-infected adult patients who had a previous mild or moderate reaction to cotrimoxazole. However, more data are needed for these results to be conclusive. It is important to note that reintroduction of cotrimoxazole was usually successful using either desensitization or rechallenge, with 44.4% to 79.4% of patients still on cotrimoxazole after six months in the three studies. Furthermore, in the studies reviewed, no strategy resulted in severe hypersensitivity reactions. Severe limitations of this review included the absence of data in paediatric populations and the minimal data from resource-poor populations."
    },
    {
        "index": "cochrane-simplification-test-158",
        "sentence": "We included in the review three trials enrolling 148 neonates. We identified no new trials for this update. Using different sedation scales, each study showed a statistically significantly higher sedation level in the midazolam group compared with the placebo group. However, none of the sedation scales used have been validated in preterm infants; therefore, we could not ascertain the effectiveness of midazolam in this population. Duration of NICU stay was significantly longer in the midazolam group than in the placebo group (WMD 5.4 days, 95% CI 0.40 to 10.5; I2 = 0%; two studies, 89 infants). One study (43 infants) reported significantly lower Premature Infant Pain Profile (PIPP) scores during midazolam infusion than during dextrose (placebo) infusion (MD -3.80, 95% CI -5.93 to -1.67). Another study (46 infants) observed a higher incidence of adverse neurological events at 28 days' postnatal age (death, grade III or IV IVH or PVL) in the midazolam group compared with the morphine group (RR 7.64, 95% CI 1.02 to 57.21; RD 0.28, 95% CI 0.07 to 0.49; NNTH 4, 95% CI 2 to 14) (tests for heterogeneity not applicable). We considered these trials to be of moderate quality according to GRADE assessment based on the following outcomes: mortality during hospital stay, length of NICU stay, adequacy of analgesia according to PIPP scores and poor neurological outcomes by 28 days' postnatal age. Data are insufficient to promote the use of intravenous midazolam infusion as a sedative for neonates undergoing intensive care. This review raises concerns about the safety of midazolam in neonates. Further research on the effectiveness and safety of midazolam in neonates is needed.",
        "gold": "We have selected for inclusion in this review randomised controlled trials of continuous intravenous drip of midazolam as a sedative in babies aged 28 days or younger. We included three clinical trials in this review. Using different scales to measure level of sedation, each study showed that midazolam was effective in providing sedation to babies. However, the validity of the sedation scales used in these studies has not been proven in babies; therefore, we cannot be certain that midazolam is, in fact, an effective sedative for babies. Moreover, one study showed that babies who received midazolam had a significantly higher risk of death or brain injury, and combined results of two studies showed that midazolam use may prolong length of stay in the NICU. One of the studies included in this review received support from industry, and for the other two studies, industry provided all study drugs. We assessed the quality of the evidence on the outcomes of mortality during hospital stay, length of stay in the NICU, pain, and neurological outcomes at 28 days of life and found the evidence to be of moderate quality, as there was not enough evidence available. Therefore, we conclude there is not enough evidence to support the use of midazolam as a sedative for babies undergoing intensive care. Additional research is needed to address the safety and effectiveness of midazolam in this population."
    },
    {
        "index": "cochrane-simplification-test-159",
        "sentence": "Twelve trials involving 767 participants were included. No differences were detected between the antibiotic and placebo/no treatment arms for people with diarrhoea at two to four days after treatment (risk ratio (RR) 1.75, 95% confidence interval (CI) 0.42 to 7.21; one trial, 46 participants; very low quality evidence). No difference was detected for the presence of diarrhoea at five to seven days after treatment (RR 0.83, 95% CI 0.62 to 1.12; two trials, 192 participants; very low quality evidence), clinical failure (RR 0.88, 95% CI 0.62 to 1.25; seven trials, 440 participants; very low quality evidence). The mean difference for diarrhoea was 0 days (95% CI -0.54 to 0.54; 202 participants, four studies; low quality evidence);for fever was 0.27 days (95% CI -0.11 to 0.65; 107 participants, two studies; very low quality evidence); and for duration of illness was 0 days (95% CI -0.68 to 0.68; 116 participants, two studies; very low quality evidence). Quinolone antibiotic treatment resulted in a significantly higher number of negative stool cultures for NTS during the first week of treatment (microbiological failure: RR 0.33, 95% CI 0.20 to 0.56; 166 participants, four trials). Antibiotic treatment meant passage of the same Salmonella serovar one month after treatment was almost twice as likely (RR 1.96, 95% CI 1.29 to 2.98; 112 participants, three trials), which was statistically significant. Non-severe adverse drug reactions were more common among the patients who received antibiotic treatment. There is no evidence of benefit for antibiotics in NTS diarrhoea in otherwise healthy people. We are uncertain of the effects in very young people, very old people, and in people with severe and extraintestinal disease. A slightly higher number of adverse events were noted in people who received antibiotic treatment for NTS.",
        "gold": "In this review, we investigated the benefits and safety of antibiotics for treatment of NTS versus placebo or no antibiotic treatment. We found that in otherwise healthy people, treatment with antibiotics did not have any benefit over treatment with no antibiotics. Furthermore, treatment with antibiotics made it more likely that patients would continue to excrete the same organisms for up to one month after treatment. We are unable to comment on the use of antibiotics in very young people, very old people and people who are unable to fight off infection because the trials we identified did not include these patients."
    },
    {
        "index": "cochrane-simplification-test-160",
        "sentence": "We included 23 studies (n = 4192) assessing the accuracy of IL-6 for the diagnosis of sepsis in critically ill adults. Twenty studies that were available as conference proceedings only are awaiting classification. The included participants were heterogeneous in terms of their distribution of age, gender, main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and origin of infection, among other factors. Prevalence of sepsis greatly varied across studies, ranging from 12% to 78%. We considered all studies to be at high risk of bias due to issues related to the index test domain in QUADAS-2. The SROC curve showed a great dispersion in individual studies accuracy estimates (21 studies, 3650 adult patients), therefore the considerable heterogeneity in the collected data prevented us from calculating formal accuracy estimates. Using a fixed prevalence of sepsis of 50% and a fixed specificity of 74%, we found a sensitivity of 66% (95% confidence interval 60 to 72). If we test a cohort 1000 adult patients under suspicion of sepsis with IL-6, we will find that 330 patients would receive appropriate and timely antibiotic therapy, while 130 patients would be wrongly considered to have sepsis. In addition, 370 out of 1000 patients would avoid unnecessary antibiotic therapy, and 170 patients would have been undiagnosed of sepsis. This numerical approach should be interpreted with caution due to the limitations described above. Our evidence assessment of plasma interleukin-6 concentrations for the diagnosis of sepsis in critically ill adults reveals several limitations. High heterogeneity of collected evidence regarding the main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and the origin of infection, among other factors, along with the potential number of misclassifications, remain significant constraints for its implementation. The 20 conference proceedings assessed as studies awaiting classification may alter the conclusions of the review once they are fully published and evaluated. Further studies about the accuracy of interleukin-6 for the diagnosis of sepsis in adults that apply rigorous methodology for conducting diagnostic test accuracy studies are needed. The conclusions of the review will likely change once the 20 studies pending publication are fully published and included.",
        "gold": "We performed a thorough literature search for studies reporting the use of IL-6 levels for detection of sepsis up to January 2019. We found 23 studies enrolling 4192 severely ill adults. Our assessment of the evidence reveals the complexity of the research topic, represented in the high variability of information reported by the studies. We found the characteristics of assessed patients to vary considerably between studies in terms of age, gender, setting, initial diagnosis, indicative value for sepsis, and source of infection, among other factors. This variability in the collected data prevented a formal numerical synthesis of the findings. Using the available data to perform an approximated estimation of the consequences, we found that 700 out of 1000 patients under suspicion of sepsis might be correctly classified, but 130 out of 1000 patients would be wrongly considered as having sepsis, while 170 out of 1000 patients might be incorrectly considered as not having sepsis. These errors would result in a serious increase in the risk of further morbidity and death due to delays of adequate treatment. This information should be interpreted with caution due to limitations in the collected data. We judged the included studies to have important limitations in their validity, hence they are at high risk of providing distorted results (i.e. to be at high risk of bias)."
    },
    {
        "index": "cochrane-simplification-test-161",
        "sentence": "We included 29 trials (5718 participants). All studies except one were at an unclear or high risk of bias. Studies were small, reported low numbers of SSI events and were often not clearly reported. There were 16 trials that included people with wounds resulting from surgical procedures with a 'clean' classification, five trials that included people undergoing what was considered 'clean/contaminated' surgery, with the remaining studies including people undergoing a variety of surgical procedures with different contamination classifications. Four trials compared wound dressings with no wound dressing (wound exposure); the remaining 25 studies compared alternative dressing types, with the majority comparing a basic wound contact dressing with film dressings, silver dressings or hydrocolloid dressings. The review contains 11 comparisons in total. Primary outcome: SSI It is uncertain whether wound exposure or any dressing reduces or increases the risk of SSI compared with alternative options investigated: we assessed the certainty of evidence as very low for most comparisons (and low for others), with downgrading (according to GRADE criteria) largely due to risk of bias and imprecision. We summarise the results of comparisons with meta-analysed data below: - film dressings compared with basic wound contact dressings following clean surgery (RR 1.34, 95% CI 0.70 to 2.55), very low certainty evidence downgraded once for risk of bias and twice for imprecision. - hydrocolloid dressings compared with basic wound contact dressings following clean surgery (RR 0.91, 95% CI 0.30 to 2.78), very low certainty evidence downgraded once for risk of bias and twice for imprecision. - hydrocolloid dressings compared with basic wound contact dressings following potentially contaminated surgery (RR 0.57, 95% CI 0.22 to 1.51), very low certainty evidence downgraded twice for risk of bias and twice for imprecision. - silver-containing dressings compared with basic wound contact dressings following clean surgery (RR 1.11, 95% CI 0.47 to 2.62), very low certainty evidence downgraded once for risk of bias and twice for imprecision. - silver-containing dressings compared with basic wound contact dressings following potentially contaminated surgery (RR 0.83, 95% CI 0.51 to 1.37), very low certainty evidence downgraded twice for risk of bias and twice for imprecision. Secondary outcomes There was limited and low or very low certainty evidence on secondary outcomes such as scarring, acceptability of dressing and ease of removal, and uncertainty whether wound dressings influenced these outcomes. It is uncertain whether covering surgical wounds healing by primary intention with wound dressings reduces the risk of SSI, or whether any particular wound dressing is more effective than others in reducing the risk of SSI, improving scarring, reducing pain, improving acceptability to patients, or is easier to remove. Most studies in this review were small and at a high or unclear risk of bias. Based on the current evidence, decision makers may wish to base decisions about how to dress a wound following surgery on dressing costs as well as patient preference.",
        "gold": "We conducted a review of all available, relevant evidence about the impact of dressings on the prevention of surgical site infections in surgical wounds healing by primary intention. This review examined data from 29 randomised controlled trials (which provide the most reliable evidence). These investigated the use of dressings in surgery that had a low risk of surgical site infection (clean surgery) and surgery with a higher risk (potentially contaminated surgery). We found no clear evidence to suggest that one dressing type was better than any other at reducing the risk of surgical site infection, nor that covering wounds with any dressing at all reduced the risk of surgical site infection. Additionally, there was no clear evidence that any dressing type improves scarring, pain control, patient acceptability or ease of removal. Currently decision makers may opt to make decisions about whether and how to dress a wound based on patient and clinician preferences and dressing costs. It is important to note that many trials in this review were small and the evidence was of low or very low certainty meaning that current information is uncertain. Assessed as up to date September 2016."
    },
    {
        "index": "cochrane-simplification-test-162",
        "sentence": "We included two randomised controlled trials. One trial compared oral 100 microgram (\u00b5g) selenium yeast tablets with placebo, taken from the first trimester until birth. The trial randomised 179 women but outcome data were only provided for 85 women. Eighty-three women were randomised to each arm of the trial. Sixty-one women completed the selenium arm, 44 of whom completed an Edinburgh Postnatal Depression Scale (EPDS). In the placebo arm, 64 women completed the trial, 41 of whom completed an EPDS. This included study (n = 85) found selenium had an effect on EPDS scores but did not reach statistical significance (P = 0.07). There was a mean difference (MD) of -1.90 (95% confidence interval (CI) -3.92 to 0.12) of the self-reported EPDS completed by participants within eight weeks of delivery. There was a high risk of attrition bias due to a large proportion of women withdrawing from the study or not completing an EPDS. This included study did not report on any of the secondary outcomes of this review. The other trial compared docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA) with placebo. The trial randomised 126 women at risk of postpartum depression to three arms: 42 were allocated to EPA, 42 to DHA, and 42 to placebo. Three women in the EPA arm, four in the DHA arm, and one woman in the placebo arm were lost to follow-up. Women who were found to have major depressive disorder, bipolar disorder, current substance abuse or dependence, suicidal ideation or schizophrenia at recruitment were excluded from the study. The women who discontinued the intervention (five in the EPA arm, four in the DHA arm and seven in the placebo arm) were included in the intention-to-treat analysis, while those who were lost to follow-up were not. Women received supplements or placebo from recruitment at a gestational age of 12 to 20 weeks until their final review visit six to eight weeks postpartum. The primary outcome measure was the Beck Depression Inventory (BDI) score at the fifth visit (six to eight weeks postpartum). No benefit was found for EPA-rich fish oil (MD 0.70, 95% CI -1.78 to 3.18) or DHA-rich fish oil supplementation (MD 0.90, 95% CI -1.33 to 3.13) in preventing postpartum depression. No difference was found in the effect on postnatal depression comparing EPA with DHA (MD -0.20, 95% CI -2.61 to 2.21). No benefit or significant effect was found in terms of the secondary outcomes of the presence of major depressive disorder at six to eight weeks postpartum, the number of women who commenced antidepressants, maternal estimated blood loss at delivery or admission of neonates to the neonatal intensive care unit. There is insufficient evidence to conclude that selenium, DHA or EPA prevent postnatal depression. There is currently no evidence to recommend any other dietary supplement for prevention of postnatal depression.",
        "gold": "This review identified two randomised controlled studies. One study examined the effect of selenium supplements taken by women from the first trimester to birth in preventing postnatal depression. This study had a high risk of bias because of women withdrawing or not completing their self-scoring system for depression (Edinburgh Postnatal Depression Scale). It may also have been difficult to ensure that the women took their supplements because of concerns that exist about taking supplements during pregnancy. More high-quality studies would be required to confirm any benefit in preventing postnatal depression using selenium. This review also identified one randomised controlled study that compared docosahexanoic and eicosapentaenoic acid to placebo in women at risk of postpartum depression. This study found that neither docosahexanoic acid nor eicosapentaenoic acid prevented postpartum depression. Overall, there is not enough evidence at this stage to recommend selenium, docosahexanoic acid, eicosapentaenoic acid or any other dietary supplement for the prevention of postnatal depression. Unfortunately there were no other studies of other dietary supplements that met our selection criteria. Other dietary supplements need to be studied in trials where depressed women are excluded from entry to determine if supplements prevent postnatal depression."
    },
    {
        "index": "cochrane-simplification-test-163",
        "sentence": "We identified 11 studies: 7 evaluated different infusion durations (803 participants), and 4 evaluated different peak doses (5280 participants). Seven studies were RCTs addressing different anthracycline infusion durations; we identified long-term follow-up data for one of the trials in this update. The meta-analysis showed a statistically significant lower rate of clinical heart failure with an infusion duration of six hours or longer as compared to a shorter infusion duration (risk ratio (RR) 0.27; 95% confidence interval 0.09 to 0.81; 5 studies; 557 participants). The majority of participants included in these studies were adults with different solid tumours. For different anthracycline peak doses, we identified two RCTs addressing a doxorubicin peak dose of less than 60 mg/m2 versus 60 mg/m2 or more, one RCT addressing a liposomal doxorubicin peak dose of 25 mg/m2 versus 50 mg/m2, and one RCT addressing an epirubicin peak dose of 83 mg/m2 versus 110 mg/m2. A significant difference in the occurrence of clinical heart failure was identified in none of the studies. The participants included in these studies were adults with different solid tumours. High or unclear 'Risk of bias' issues were present in all studies. An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure, and it seems to reduce the risk of subclinical cardiac damage. Since there is only a small amount of data for children and data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children. We identified no significant difference in the occurrence of clinical heart failure in participants treated with a doxorubicin peak dose of less than 60 mg/m2 or 60 mg/m2 or more. Only one RCT was available for the other identified peak doses, so we can make no definitive conclusions about the occurrence of cardiotoxicity. More high-quality research is needed, both in children and adults and in leukaemias and solid tumours.",
        "gold": "The evidence is current to December 2015. We found 11 studies: 7 evaluated different infusion durations (803 participants), and 4 evaluated different peak doses (5280 participants). Participants had different types of cancer. For the use of different anthracycline infusion durations, the authors found that an anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure (for example shortness of breath or leg oedema), and it seems to reduce the risk of subclinical heart failure (that is heart damage diagnosed for example by an echocardiography in people without symptoms). Only a small amount of data was available for children and individuals with leukaemia, since most studies evaluating different anthracycline infusion durations were performed in adults with solid tumours. Based on the currently available evidence, we are not able to favour either a doxorubicin peak dose of less than 60 mg/m2 or 60 mg/m2 or more. There was not enough high-quality evidence available for the use of other anthracycline peak doses to be able to draw conclusions. No data were available for children and individuals with leukaemia. Further high-quality research is needed. All studies had problems relating to quality of the evidence."
    },
    {
        "index": "cochrane-simplification-test-164",
        "sentence": "We included 37 eligible trials with a total of 3110 randomised participants; nine of these were new studies since the last update (2009) and five studies had been previously excluded but were re-assessed and included during the 2017 update. We identified two ongoing studies from searches of clinical trials registers and database searches and two studies await classification. Studies included both adults and children with TBI. Most studies commenced treatment immediately on admission to hospital or after craniotomies and all treatment was maintained for at least 24 hours. Thirty-three studies reported data for mortality, 31 studies reported data for unfavourable outcomes (death, vegetative state or severe disability), and 14 studies reported pneumonia. Visual inspection of the results for these outcomes showed inconsistencies among studies, with differences in the direction of effect, and we did not pool these data for meta-analysis. We considered duration of hypothermia therapy and the length of follow-up in collected data for these subgroups; differences in study data remained such that we did not perform meta-analysis. Studies were generally poorly reported and we were unable to assess risk of bias adequately. Heterogeneity was evident both in the trial designs and participant inclusion. Inconsistencies in results may be explained by heterogeneity among study participants or bias introduced by individual study methodology but we did not explore this in detail in subgroup or sensitivity analyses. We used the GRADE approach to judge the quality of the evidence for each outcome and downgraded the evidence for mortality and unfavourable outcome to very low. We downgraded the evidence for the pneumonia outcome to low. Despite a large number studies, there remains no high-quality evidence that hypothermia is beneficial in the treatment of people with TBI. Further research, which is methodologically robust, is required in this field to establish the effect of hypothermia for people with TBI.",
        "gold": "We included 37 studies with 3110 participants. In each trial, patients were randomly divided into two groups: one group remained at normal body temperature of 36.5 to 38 \u00b0C, and the other group was cooled to a maximum of 35 \u00b0C for at least 12 hours. We did not combine results of these studies to assess whether hypothermia improves patient outcome. This was because the results had large differences which we could not explain. We identified some differences in the ways in which the studies were carried out and the participants that study authors had recruited, but we did not assess whether this could explain the differences in results. We did not have enough good quality evidence that was sufficiently similar to be confident that treating people who have had a severe brain injury with hypothermia will reduce the incidence of death or severe disability, or increase the incidence of pneumonia. Many of the studies were not well reported and we were unable to assess whether differences between the quality of the studies may also have affected our results. We used the GRADE approach to judge the quality of evidence. We judged the evidence for death or severe disability to be very low quality, and the evidence for pneumonia to be low quality."
    },
    {
        "index": "cochrane-simplification-test-165",
        "sentence": "Three high-quality and three low-quality studies, involving 519 people with depression, were identified. The studies were very heterogeneous in terms of interventions, participants, and measuring instruments. Despite fairly good methodological quality and positive findings of some studies, evidence for the effectiveness of family therapy for depression did not exceed level 3 (limited or conflicting evidence), except for moderate evidence (level 2), based on the non-combined findings from three studies, indicating that family therapy is more effective than no treatment or waiting list condition on decreasing depression, and on increasing family functioning. The current evidence base is too heterogeneous and sparse to draw conclusions on the overall effectiveness of family therapy in the treatment of depression. At this point, use of psychological interventions for the treatment of depression for which there is already an evidence-base would seem to be preferable to family therapy. Further high quality trials examining the effectiveness and comparative effectiveness of explicitly defined forms of family therapy are required.",
        "gold": "This review looks at whether family therapy is an effective intervention in treating people of any age with depression. Family therapy for depression is widely used, especially in the United Kingdom and the United States. The small number of randomised controlled trials included in the review were very heterogeneous, and therefore difficult to synthesise. Family therapy seems more effective than no treatment or being placed on a waiting list, but it remains unclear how effective this intervention is in comparison to other interventions. Further randomised controlled trials are needed."
    },
    {
        "index": "cochrane-simplification-test-166",
        "sentence": "Three trials involving a total of 206 participants were included, all patients with vascular dementia. All three included studies were assessed as being at high risk of bias. When analysing these trials together, there was significant beneficial effect of Duxil on the improvement of cognitive function measured by MMSE (WMD 2.04, 95% CI 1.43 to 2.66). No data on behaviour and death at the end of treatment and follow-up were available from the included trials. Two trials failed to show an improvement of functional performance measured by ADL (WMD -1.68; 95% CI -3.70 to 0.35). Of the three included trials, all described the adverse events in detail, there were no statistically significant differences across the trials (OR 4.84, 95%CI 0.55 to 42.67). Behaviour disturbance, quality of life, caregiver burden were not undertaken in the included trials. Due to the low methodological quality of included trials, small number of trials and probable publication bias, this review did not provide sufficient evidence to support the routine use of Duxil for the treatment of patients with dementia. High-quality and large-scale randomised controlled trials are needed to confirm or refute these results.",
        "gold": "Duxil is described as having several properties which may be beneficial for dementia. This review looked for randomized trials comparing Duxil with control in patients with dementia. Three trials were identified. Though there was significant beneficial effect of Duxil on the improvement of cognitive function, due to the low methodological quality of included trials, small number of trials and probable publication bias, this review did not provide sufficient evidence to support the routine use of Duxil for the treatment of patients with dementia. More large, high-quality randomized trials are needed."
    },
    {
        "index": "cochrane-simplification-test-167",
        "sentence": "Seven RCTs including 960 participants were identified. The quality of trials was generally low, with several studies at risk of selection bias, and no studies used blinding during treatment or outcome assessment. There was a high level of statistical variation between the studies, which therefore reduces the reliability of the evidence. The OR for seroma formation was 0.46 (95% confidence interval (CI) 0.23 to 0.91, P = 0.03) in favour of a reduced incidence of seroma in participants with drains inserted. There was no significant difference in infection rates between drainage and no drainage groups (OR = 0.70; 95% CI 0.44 to 1.12, P = 0.14). The mean difference in length of hospital stay, reported in four trials consisting of 600 participants, was 1.47 days greater in the drained population (95% CI 0.67 to 2.28, P = 0.0003). A mean difference of 0.79 fewer postoperative seroma aspirations was found in the drained population (95% CI 1.23 to 0.35 fewer, P = 0.0004) in two trials including 212 participants. No significant difference in volume of seroma aspirations was reported (MD -19.44, 95% CI -59.45 to 20.57, P = 0.34) in three trials including 519 participants. No significant difference in the incidence of lymphoedema was noted (OR 2.31 favouring no drainage, 95% CI 0.47 to 11.37, P = 0.30), with only six instances reported in three trials of 360 participants, nor was any significant difference in the incidence of haematoma observed (OR 1.68, 95% CI 0.33 to 8.51, P = 0.53), with only five instances reported in two trials of 314 participants. There is limited quality evidence that insertion of a drain following axillary lymphadenectomy reduced the odds of developing a seroma and reduced the number of post-operative seroma aspirations. These benefits should be balanced against an increased length of hospital stay in the drained population.",
        "gold": "This Cochrane review aims to determine whether drain tube insertion reduces complication rates or is associated with any risks or harms. We analysed seven randomised controlled trials including 960 participants that compared drain insertion with no drainage after axillary lymphadenectomy for the treatment of breast cancer. We found that the chance of getting a seroma if a drain was inserted was less than if no drain was inserted (0.46 times less likely), and that the number of aspirations required (using a needle to drain seroma fluid in the outpatient clinic) was lower (on average, 0.79 fewer per participant). These benefits must be balanced against a longer average hospital stay of 1.47 days in the drained population, although increasingly patients can be discharged with their drain in place, to be removed at a later date. Risk of infection, volume of fluid aspirated and rates of lymphoedema (arm swelling) or haematoma (bruising) did not differ between drained and undrained participants."
    },
    {
        "index": "cochrane-simplification-test-168",
        "sentence": "Eight studies with 390,769 participants were included. Five studies used a prospective cohort design, two were case-control studies and one a randomised controlled trial (RCT). The methodological quality was measured using the Newcastle-Ottawa scale (NOS). The three prospective cohort studies were of high methodological quality, and two were of medium quality. The two case-control studies were of medium methodological quality. The results form the studies assessing associations between flavonoids, colorectal cancer and adenomas were contradictory. There was no evidence that total flavonoid intake reduced the risk of colorectal neoplasms. The evidence for Isoflavones, Flavonols, Flavones and Flavanones was conflicting. For Flavan-3-ols, the results from two studies suggested that increased intake of Flavan-3-ols reduced the risk of both CRC and colorectal adenomas. A statistically significant reduced risk of CRC was found with high intake of epicatechin. There was medium quality evidence to support that increased intake of procyanidin and phytoestrogen could reduced the incidence of CRC. There was no evidence that suggested that high anthocyanin intake had an inverse association with colorectal adenomas. There is insufficient and conflicting evidence regarding flavonoid intake and the prevention of colorectal neoplasms. It is difficult to determine flavonoid intake. Therefore, more evidence is needed to clarify the association between flavonoids and colorectal neoplasms.",
        "gold": "Eight studies with 390,769 participants, mainly observational, were included in this systematic review. The aim of the studies reviewed was to determine an association of the intake of total flavonoids, and eight main flavonoid subclasses, with colorectal neoplasms including CRC and adenomas. The majority of the studies were of medium to high methodological quality. The evidence that intake of dietary flavonoids reduces the risk of colorectal neoplasms was conflicting, and could partly be explained due to difficulties in quantifying the intake of flavonoids. Therefore, the association of dietary flavonoids and prevention of colorectal neoplasms remains unproven."
    },
    {
        "index": "cochrane-simplification-test-169",
        "sentence": "We included seven trials with 1369 participants. All trials had high risk of bias. Five trials used our first definition of slow responders, and three other trials (including one that used both definitions) used the second definition. None of the included trials mentioned our primary outcomes. However, regarding the secondary outcomes, extension of the treatment period to 72 weeks increased the sustained virological response according to both definitions (71/217 (32.7%) versus 52/194 (26.8%); risk ratio (RR) 1.43, 95% confidence interval (CI) 1.07 to 1.92, P = 0.02, I2 = 8%; and 265/499 (53.1%) versus 207/496 (41.7%); RR 1.27, 95% CI 1.07 to 1.50, P = 0.006, I2 = 38%), with a risk difference of 0.11 and calculated number needed to treat of nine. The end of treatment response was not significantly different between the two treatment groups. The number of participants who relapsed virologically was found to be lower in the groups that had been treated for 72 weeks using both definitions (27/84 (32.1%) versus 46/91 (50.5%); RR 0.59, 95% CI 0.40 to 0.86, P = 0.007, I2 = 18%, 3 trials; and 85/350 (24.3%) versus 146/353 (41.4%); RR 0.59, 95% CI 0.47, 0.73, P < 0.000001, I2 = 0%, 3 trials). The length of treatment did not significantly affect the adherence (247/279 (88.5%) versus 252/274 (92.0%); RR 0.95, 95% CI 0.84 to 1.07, P = 0.42, I2 = 69%, 3 trials). In the single trial that reported adverse events, no significant difference was seen between the two treatment groups. This review demonstrates higher a proportion of sustained virological response after extension of treatment from 48 weeks to 72 weeks in HCV genotype 1 infected patients in whom HCV RNA was still detectable but decreased by \u2265 2 log after 12 weeks and became negative after 24 weeks of treatment, and in patients with detectable HCV RNA after four weeks of treatment with peginterferon plus ribavirin. The observed intervention effects can be caused by both systematic error (bias) and random errors (play of chance). There was no reporting on mortality and the reporting of clinical outcomes and adverse events was insufficient. More data are needed in order to recommend or reject the policy of extending the treatment period for slow responders.",
        "gold": "We found seven randomised clinical trials that compared a treatment duration of 72 weeks with 48 weeks in 1369 participants. The quality of all trials was low. Mortality and liver-related morbidity were not reported in any of the included trials. Sustained virological response (that is, undetectable hepatitis C virus RNA after six months from the end of an entire course of treatment) was increased when the decision to prolong treatment was taken based on viral load after 12 weeks of treatment (RR 1.43, 95% CI 1.07 to 1.92) as well as when the decision to prolong treatment was taken based on the results of the viral load after four weeks of treatment (RR 1.27, 95% CI 1.07 to 1.50). The calculated number needed to treat to achieve an increase in sustained virological response proportions was nine (meaning that among nine participants treated for 72 weeks instead of 48 weeks, only one more will achieve a sustained virological response compared to the participants treated for 48 weeks). The higher sustained virological response after 72 weeks of treatment was caused by a reduction in the number of patients in this group who experienced a virological relapse after treatment. Adherence to treatment was not different between the two groups. Serious adverse events were mentioned in only one trial, and they were not different in the two treatment groups. The findings may be influenced by both risks of systematic errors (bias) and the risk of random errors (play of chance). Further large-scale, randomised trials with reporting of patient relevant outcomes are warranted."
    },
    {
        "index": "cochrane-simplification-test-170",
        "sentence": "Only two studies (34 participants) met the inclusion criteria of this systematic review. Both studies evaluated the diagnostic test accuracy of EUS in assessing the resectability with curative intent in pancreatic cancers. There was low concerns about applicability for most domains in both studies. The overall risk of bias was low in one study and unclear or high in the second study. The mean probability of unresectable disease after CT scan across studies was 60.5% (that is 61 out of 100 patients who had resectable cancer after CT scan had unresectable disease on laparotomy). The summary estimate of sensitivity of EUS for unresectability was 0.87 (95% confidence interval (CI) 0.54 to 0.97) and the summary estimate of specificity for unresectability was 0.80 (95% CI 0.40 to 0.96). The positive likelihood ratio and negative likelihood ratio were 4.3 (95% CI 1.0 to 18.6) and 0.2 (95% CI 0.0 to 0.8) respectively. At the mean pre-test probability of 60.5%, the post-test probability of unresectable disease for people with a positive EUS (EUS indicating unresectability) was 86.9% (95% CI 60.9% to 96.6%) and the post-test probability of unresectable disease for people with a negative EUS (EUS indicating resectability) was 20.0% (5.1% to 53.7%). This means that 13% of people (95% CI 3% to 39%) with positive EUS have potentially resectable cancer and 20% (5% to 53%) of people with negative EUS have unresectable cancer. Based on two small studies, there is significant uncertainty in the utility of EUS in people with pancreatic cancer found to have resectable disease on CT scan. No studies have assessed the utility of EUS in people with periampullary cancer. There is no evidence to suggest that it should be performed routinely in people with pancreatic cancer or periampullary cancer found to have resectable disease on CT scan.",
        "gold": "We included two studies with a total of 34 patients in this review. Both studies evaluated the diagnostic performance of EUS. This evidence is current to 5 November 2015. Of the two studies, one study was conducted as well as such a study could be conducted. The methodological quality of the other study was poor. The two included studies showed that in those people with pancreatic cancer in whom CT alone showed their cancer was capable of being fully surgically removed, 61% (61 out of 100) would prove to have cancer that was too fully spread to make this possible when a laparotomy was attempted. Due to the small sample size, there is significant uncertainty in the utility of EUS in people with pancreatic cancer found to have resectable disease on CT scan. There is no evidence to suggest that it should be performed routinely in people with pancreatic cancer found to have resectable disease on CT scan."
    },
    {
        "index": "cochrane-simplification-test-171",
        "sentence": "There were 34 studies (2169 participants with blepharitis) included in this review: 20 studies (14 RCTs and 6 CCTs) included 1661 participants with anterior or mixed blepharitis and 14 studies (12 RCTs and 2 CCTs) included 508 participants with posterior blepharitis (MGD). Due to the heterogeneity of study characteristics among the included studies, with respect to follow-up periods and types of interventions, comparisons, and condition of participants, our ability to perform meta-analyses was limited. Topical antibiotics were shown to provide some symptomatic relief and were effective in eradicating bacteria from the eyelid margin for anterior blepharitis. Lid hygiene may provide symptomatic relief for anterior and posterior blepharitis. The effectiveness of other treatments for blepharitis, such as topical steroids and oral antibiotics, were inconclusive. Despite identifying 34 trials related to treatments for blepharitis, there is no strong evidence for any of the treatments in terms of curing chronic blepharitis. Commercial products are marketed to consumers and prescribed to patients without substantial evidence of effectiveness. Further research is needed to evaluate the effectiveness of such treatments. Any RCT designed for this purpose should separate participants by type of condition (e.g. staphylococcal blepharitis or MGD) in order to minimize imbalances between groups (type I errors) and to achieve statistical power for analyses (prevent type II errors). Medical interventions and commercial products should be compared with conventional lid hygiene measures, such as warm compresses and eyelid margin washing, to determine effectiveness, as well as head-to-head to show comparative effectiveness between treatments. Outcomes of interest should be patient-centered and measured using validated questionnaires or scales. It is important that participants be followed long-term, at least one year, to assess chronic outcomes properly.",
        "gold": "This review focuses on chronic blepharitis and stratifies anterior and posterior blepharitis. There were 34 studies (2169 participants with blepharitis) included in the review, 20 of which included participants with anterior blepharitis and 14 of which included participants with posterior blepharitis. For anterior blepharitis, topical antibiotics provided some symptomatic relief and were effective in clearing bacteria from the eyelid margins. There was no difference between the types of topical antibiotics used. Topical steroids also provided some symptomatic relief; however, they were ineffective in eliminating bacteria. Lid hygiene, including warm compresses and lid scrubs, showed some symptomatic relief in both anterior and posterior blepharitis. Overall, there was no strong evidence for any of the treatments in terms of curing chronic blepharitis. Further research should be done to evaluate the effectiveness of treatments for blepharitis, with particular attention paid to adequate diagnosis and classification of the disease."
    },
    {
        "index": "cochrane-simplification-test-172",
        "sentence": "We included one trial with a total of 23 participants. This study was at high risk of bias. None of our primary outcomes and only one of our secondary outcomes (reduction in volume of disease, assessed endoscopically) was measured in the study. There was no significant difference between the groups (very low-quality evidence). Adverse effects reported included airway swelling requiring intubation in a child with severe RRP a few hours after photodynamic therapy. There is insufficient evidence from high-quality randomised controlled trials to determine whether photodynamic therapy alters the course of disease or provides an added benefit to surgery in patients with recurrent respiratory papillomatosis. Multicentre randomised controlled trials with appropriate sample sizes and long-term follow-up are required to evaluate whether photodynamic therapy is of benefit. Outcomes such as improvement in symptoms (respiratory function and voice quality) and quality of life should be measured in future trials.",
        "gold": "We found one randomised controlled trial with a total of 23 participants for inclusion in this review. The study took place at two centres in the USA. Six of the 23 patients did not complete the study (dropped out). Participants who completed the study were outpatients, their age range was four to 60 years and 76% were men and 24% women. The study did not measure any of the outcomes important to patients (symptom improvement - respiratory distress/dyspnoea and voice quality, quality of life improvement and recurrence-free interval). It did measure the reduction in the volume of disease (assessed with an endoscope). We found insufficient evidence from the included study that photodynamic therapy has a benefit on its own or in combination with surgery in recurrent respiratory papillomatosis. There was no clear evidence that effects observed in the treatment group were different to those in the control group. Adverse effects reported included airway swelling in a child with severe disease a few hours after photodynamic therapy, which required insertion of a breathing tube and a prolonged stay in hospital. The overall quality of the evidence is very low: there was no blinding of treatment and a high rate of drop-out. This evidence is up to date to January 2014."
    },
    {
        "index": "cochrane-simplification-test-173",
        "sentence": "We identified 42 primary studies with 4220 participants. Twenty studies provided accuracy data based on the number of individual participants (seven of which provided data with and without the use of contrast). Sixteen of these studies evaluated the accuracy of CDUS. These studies were generally of moderate to low quality: only three studies fulfilled all the QUADAS items; in six (40%) of the studies, the delay between the tests was unclear or longer than four weeks; in eight (50%), the blinding of either the index test or the reference standard was not clearly reported or was not performed; and in two studies (12%), the interpretation of the reference standard was not clearly reported. Eleven studies evaluated the accuracy of CE-CDUS. These studies were of better quality than the CDUS studies: five (45%) studies fulfilled all the QUADAS items; four (36%) did not report clearly the blinding interpretation of the reference standard; and two (18%) did not clearly report the delay between the two tests. Based on the bivariate model, the summary estimates for CDUS were 0.82 (95% confidence interval (CI) 0.66 to 0.91) for sensitivity and 0.93 (95% CI 0.87 to 0.96) for specificity whereas for CE-CDUS the estimates were 0.94 (95% CI 0.85 to 0.98) for sensitivity and 0.95 (95% CI 0.90 to 0.98) for specificity. Regression analysis showed that CE-CDUS was superior to CDUS in terms of sensitivity (LR Chi2 = 5.08, 1 degree of freedom (df); P = 0.0242 for model improvement). Seven studies provided estimates before and after administration of contrast. Sensitivity before contrast was 0.67 (95% CI 0.47 to 0.83) and after contrast was 0.97 (95% CI 0.92 to 0.99). The improvement in sensitivity with of contrast use was statistically significant (LR Chi2 = 13.47, 1 df; P = 0.0002 for model improvement). Regression testing showed evidence of statistically significant effect bias related to year of publication and study quality within individual participants based CDUS studies. Sensitivity estimates were higher in the studies published before 2006 than the estimates obtained from studies published in 2006 or later (P < 0.001); and studies judged as low/unclear quality provided higher estimates in sensitivity. When regression testing was applied to the individual based CE-CDUS studies, none of the items, namely direction of the study design, quality, and age, were identified as a source of heterogeneity. Twenty-two studies provided accuracy data based on number of scans performed (of which four provided data with and without the use of contrast). Analysis of the studies that provided scan based data showed similar results. Summary estimates for CDUS (18 studies) showed 0.72 (95% CI 0.55 to 0.85) for sensitivity and 0.95 (95% CI 0.90 to 0.96) for specificity whereas summary estimates for CE-CDUS (eight studies) were 0.91 (95% CI 0.68 to 0.98) for sensitivity and 0.89 (95% CI 0.71 to 0.96) for specificity. This review demonstrates that both ultrasound modalities (with or without contrast) showed high specificity. For ruling in endoleaks, CE-CDUS appears superior to CDUS. In an endoleak surveillance programme CE-CDUS can be introduced as a routine diagnostic modality followed by CT scan only when the ultrasound is positive to establish the type of endoleak and the subsequent therapeutic management.",
        "gold": "We collected the most recent evidence (to July 2016) and conducted a meta-analysis according to the most appropriate methods for diagnostic tests. We included 42 studies with 4220 participants in the review. The analyses measured sensitivity (how well a test identified people with endoleak correctly) and specificity (how well a test identified people without endoleak correctly). The summary accuracy estimates were sensitivity 82% (95% confidence interval 66% to 91%) and specificity 93% (95% confidence interval 87% to 96%) for ultrasonography without contrast; and sensitivity 94% (95% confidence interval 85% to 98%) and specificity 95% (95% confidence interval 90% to 98%) for ultrasonography with contrast. Use of contrast improved the sensitivity of ultrasound significantly. Based on these results, we would expect 94% of people with endoleaks will be correctly identified by contrast-enhanced ultrasound. Studies that evaluated contrast-enhanced ultrasound used better methods than the studies that evaluated ultrasound alone."
    },
    {
        "index": "cochrane-simplification-test-174",
        "sentence": "We included seven studies, with 766 participants: four used intracutaneous injections, two subcutaneous, and one both. All reported on low back pain in labour only. Methodological quality was good, but four studies were at high risk of bias due to small size of treatment groups, incomplete outcome data, and performance bias. All studies reported treatment group mean or median scores, finding greater reduction in pain for sterile water. However, failure to demonstrate a normal distribution for pain intensity or relief, and use of different scales, meant meta-analysis was inappropriate. No study reported primary dichotomous efficacy outcomes. One reported the number self-scoring 4/10 cm or more reduction in pain; significantly more had this outcome with sterile water (50% to 60%) than with placebo (20% to 25%). There was no significant difference between sterile water and saline for rates of caesarean section (risk ratio (RR) 0.58, 95% confidence interval (CI) 0.33 to 1.02), instrumental delivery (RR 1.31, 95% CI 0.79 to 2.18), rescue analgesia (RR 0.86, 95% CI 0.44 to 1.69), timing of delivery, or Apgar scores. Two studies reported that more women treated with sterile water would request the same analgesia in future. No study reported on women's satisfaction with pain relief, women's sense of control in labour, women's satisfaction with the childbirth experience, mother/baby interaction, rates of breastfeeding, maternal morbidity, infant long-term outcomes, or cost. No adverse events were reported other than transient pain with injection, which was worse with sterile water. The outcomes reported severely limit conclusions for clinical practice. We found little robust evidence that sterile water is effective for low back or any other labour pain. Neither did we find any difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labour.",
        "gold": "In this review we looked at the effectiveness of injections of small amounts of sterile water given into four spots on the woman\u2019s lower back in labour. The review included seven studies with 766 participants; four used intracutaneous injections, two subcutaneous, and one both. All studies compared the injections of sterile water with injections of saline, whilst none compared the injection of sterile water with women using their own skills to manage pain in labour.\u00a0Nor did the studies compare with other forms of pain management in labour, as this information is in other Cochrane reviews. We found no good quality evidence that these simple water injections could provide a significant level of pain relief compared with simple saline injection for any type of pain experienced during labour. Women did report transient pain at the injection site. More research is needed on this possible form of pain management in labour."
    },
    {
        "index": "cochrane-simplification-test-175",
        "sentence": "Twelve trials with a total of 1932 participants were included in this review. The overall postoperative chronic pain in the glue group was reduced by 37% (OR 0.63, 95% CI 0.44 to 0.91; 10 studies, 1418 participants, low-quality evidence) compared with the suture group. However, the results changed when we conducted subgroup analysis with regard to the type of mesh. Subgroup analysis of included studies using lightweight mesh showed the reduction of chronic pain was less profound and insignificant (OR 0.77, 95% CI 0.50 to 1.17). Subgroup analysis of included studies using heavyweight mesh resulted in a significant benefit from the fixation with glue (OR 0.38, 95% CI 0.17 to 0.82). Hernia recurrence was similar between the two groups (OR 1.44, 95% CI 0.63 to 3.28; 12 studies, 1932 participants, low-quality evidence). Fixation with glue was superior to suture regarding duration of the operation (MD \u22123.13, 95% CI \u22124.48 to \u22121.78; 9 studies, 1790 participants, low-quality evidence); haematoma (OR 0.52, 95% CI 0.31 to 0.86; 10 studies, 1384 participants, moderate-quality evidence); and recovery time to daily activities (MD \u22121.26, 95% CI \u22121.89 to \u22120.63; 3 studies, 403 participants, low-quality evidence). We also investigated adverse events. There were no significant differences between the two groups. For superficial wound infection pooled analyses showed OR 1.23, 95% CI 0.37 to 4.11; 7 studies, 763 participants (low-quality evidence); for mesh/deep infection OR 0.67, 95% CI 0.16 to 2.83; 8 studies, 1393 participants (low-quality evidence). Furthermore, we investigated seroma (a postoperative swelling caused by fluid) (OR 0.83, 95% CI 0.51 to 1.33); and persisting numbness (OR 0.81, 95% CI 0.57 to 1.14). Finally, six trials involving 1009 participants reported postoperative length of stay, resulting in non-significant difference between the two groups (MD \u22120.12, 95% CI: \u22120.35 to 0.10) Due to the lack of data, it was impossible to draw any distinction between synthetic glue and biological glue. Eight out of 12 trials showed high risk of bias in at least one of the investigated domains. Two studies were quasi-randomised controlled trials and the allocation sequence of one trial was not concealed. Nearly half of the included trials either did not provide adequate information or had high risk of bias regarding blinding processes. The risk of bias for incomplete outcome data of all the included studies varied from low to high risk of bias. Two trials did not report on some important outcomes. One study was funded by the manufacturer producing the fibrin sealant. Therefore, according to the 'Summary of findings' tables, the quality of the evidence (GRADE) for the outcomes is moderate to low. Based on the short-term results, glue may reduce postoperative chronic pain and not simultaneously increase the recurrence rate, compared with sutures for mesh fixation in Lichtenstein hernia repair. Glue may therefore be a sensible alternative to suture for mesh fixation in Lichtenstein repair. Larger trials with longer follow-up and high quality are warranted. The difference between synthetic glue and biological glue should also be assessed in the future.",
        "gold": "We identified 12 relevant randomised controlled trials comparing glue versus suture for fixation of the mesh, with a total of 1932 participants. Glue fixation is superior to suture for the outcomes of chronic pain, duration of operation, haematoma and recovery time to daily activities. Glue fixation is not associated with an increased risk of infection, hernia recurrence, seroma (a collection of fluid that builds up under the surface of the skin after surgery), persisting numbness (loss of sensation or feeling), quality of life, and postoperative length of stay. We do not know the role of glue fixation in people with recurrent hernia, femoral hernia or complicated hernia. Meanwhile no conclusions could be drawn on which type of glue should be used because of lack of trials. Eight out of 12 trials showed high risk of bias in at least one of the investigated domains. Two studies were quasi-randomised controlled trials. Nearly half of the included trials either did not provide adequate information or had high risk of bias regarding blinding processes. The risk of bias for incomplete outcome data of all the included studies is low to high. Two trials did not report on some important outcomes. One study was funded by the manufacturer producing the fibrin sealant. As the quality of the evidence (GRADE) for the outcomes is moderate to low and the results of chronic pain is not robust, the findings should be interpreted with caution. However, the evidence is still sufficient to conclude that glue fixation of mesh for the Lichtenstein procedure is comparable, if not superior, to fixation with suture. Glue may be a sensible alternative to suture for mesh fixation in Lichtenstein repair."
    },
    {
        "index": "cochrane-simplification-test-176",
        "sentence": "We located 32 studies addressing technical editing and 66 surveys of reference accuracy. Only three of the studies were randomised controlled trials.   A 'package' of largely unspecified editorial processes applied between acceptance and publication was associated with improved readability in two studies and improved reporting quality in another two studies, while another study showed mixed results after stricter editorial policies were introduced. More intensive editorial processes were associated with fewer errors in abstracts and references. Providing instructions to authors was associated with improved reporting of ethics requirements in one study and fewer errors in references in two studies, but no difference was seen in the quality of abstracts in one randomised controlled trial. Structuring generally improved the quality of abstracts, but increased their length. The reference accuracy studies showed a median citation error rate of 38% and a median quotation error rate of 20%. Surprisingly few studies have evaluated the effects of technical editing rigorously. However there is some evidence that the 'package' of technical editing used by biomedical journals does improve papers. A substantial number of references in biomedical articles are cited or quoted inaccurately.",
        "gold": "Most journals try to improve articles before publication by editing them to make them fit a 'house-style', and by other processes such as proof-reading. We refer to all these processes as technical editing. We identified 32 studies of the effects of technical editing from a systematic review. There is some evidence that the overall 'package' of technical editing raises the quality of articles (suggested by 'before-and-after' studies) and that structuring abstracts makes them more useful, although longer. However, there has been little rigorous research to show which processes can improve accuracy or readability the most, or if any have harmful effects or disadvantages. Over one third of references cited in articles in medical journals have some inaccuracies and one-fifth of quotations to references in these articles are not accurate"
    },
    {
        "index": "cochrane-simplification-test-177",
        "sentence": "We included 15 studies including 721 participants with cancer pain due to diverse types of malignancy. All studies were performed on adults; there were no studies on children. The included studies were of adequate methodological quality, but all except for one were judged to be at a high risk of bias because of small study size, and six because of methods used to deal with missing data or high withdrawal rates. Three studies used a parallel group design; the remainder were cross-over trials in which there was an adequate washout period, but only one reported results for treatment periods separately. Twelve studies used codeine as a single agent and three combined it with paracetamol. Ten studies included a placebo arm, and 14 included one or more of 16 different active drug comparators or compared different routes of administration. Most studies investigated the effect of a single dose of medication, while five used treatment periods of one, seven or 21 days. Most studies used codeine at doses of 30 mg to 120 mg. There were insufficient data for any pooled analysis. Only two studies reported our preferred responder outcome of 'participants with at least 50% reduction in pain' and two reported 'participants with no worse than mild pain'. Eleven studies reported treatment group mean measures of pain intensity or pain relief; overall for these outcome measures, codeine or codeine plus paracetamol was numerically superior to placebo and equivalent to the active comparators. Adverse event reporting was poor: only two studies reported the number of participants with any adverse event specified by treatment group and only one reported the number of participants with any serious adverse event. In multiple-dose studies nausea, vomiting and constipation were common, with somnolence and dizziness frequent in the 21-day study. Withdrawal from the studies, where reported, was less than 10% except in two studies. There were three deaths, in all cases due to the underlying cancer. We identified only a small amount of data in studies that were both randomised and double-blind. Studies were small, of short duration, and most had significant shortcomings in reporting. The available evidence indicates that codeine is more effective against cancer pain than placebo, but with increased risk of nausea, vomiting, and constipation. Uncertainty remains as to the magnitude and time-course of the analgesic effect and the safety and tolerability in longer-term use. There were no data for children.",
        "gold": "In this review we set out to estimate how well codeine worked, how many people had side effects, and how severe those side effects were - for example, whether they were so severe that participants stopped taking their oral codeine. We included 15 studies with 721 participants. The studies we found had methodological shortcomings: they were small and of short duration. They also reported results in different ways, so that it was not possible to combine results. In seven of the eight studies that compared codeine with placebo, codeine was better than placebo. In studies that compared codeine with another drug, the results were similar. Codeine at doses of 30 mg to 120 mg, alone or in combination with paracetamol, does seem to provide a good level of pain relief for some people with cancer pain. We cannot be certain about how many people will get this benefit, and we do not know whether, or by how much, adding paracetamol increases its effect. Codeine increases nausea, vomiting, and constipation, and may cause drowsiness or dizziness if used for more than a week. Some people will stop taking codeine because of the side effects. More trials comparing codeine with other treatments and using patient-centred outcomes are needed. The role of codeine in mild cancer pain, in addition to moderate to severe cancer pain, should be investigated."
    },
    {
        "index": "cochrane-simplification-test-178",
        "sentence": "A total of 12 trials (11 randomized controlled trials and one quasi-randomized trial) of 563 people with HbSS, HbSC or HbS\u03b2thal, aged six to 35 years old, were included in the review; the majority of participants were African-American. Interventions ranged from a total of one hour to weekly sessions for eight weeks and the post-intervention assessments ranged from the end of the intervention period to 12 months after completion. The heterogeneity of the included trials, which encompasses setting, inclusion and exclusion criteria, interventional method and time of assessment, ranged from 'not important' to 'moderate to substantial' for different review outcomes. The overall risk of bias was low for selective reporting, unclear for random sequence generation, allocation concealment, blinding of participants and blinding of outcome assessment. Incomplete outcome reporting and blinding of personnel showed mixed bias representations. Patient knowledge was assessed by four trials (160 participants) with moderate to substantial heterogeneity. There was evidence that educational programs improved patient knowledge, standardised mean difference 0.87 points (95% confidence interval 0.28 to 1.45, moderate quality evidence), which improved further when a trial with high bias was removed in a sensitivity analysis. Caregiver knowledge, reported in a single trial of 20 families, also showed an improvement, standardised mean difference 0.52 points (95% confidence interval 0.03 to 1.00, moderate quality evidence). The effect on patient knowledge was sustained at longer follow-up periods, whereas the effect on caregiver knowledge was not sustained. There were two primary outcomes related to the effectiveness of educational programs on the recognition of signs and symptoms of disease-related morbidity. No comparative data were reported for patients or caregivers (or both) recognising signs and symptoms leading to self-management. Data from two trials were analysed for the utilization of health services and showed no evidence of an effect, mean difference 0.33 (95% confidence interval -0.57 to 1.23, moderate quality evidence). With regard to the review's secondary outcomes, depression showed a statistically significant decline in intervention groups, standardised mean difference -0.66 points (95% confidence interval -1.18, to -0.14, moderate quality evidence). Adherence to treatment was not assessed in any of the identified trials. No effects of interventions were seen on coping, family relationships or health-related quality of life of patients. The quality of evidence was low for positive coping and moderate for child knowledge, healthcare utilization and depression. This suggests that further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimates. This review identifies important positive effects of educational interventions on improving patient knowledge of sickle cell disease and depression. Effects on patients' knowledge were maintained for longer than for caregivers. The effect on knowledge was significant but small and whether it offers any clinical benefit is uncertain. Significant factors limiting these effects could be trials being under powered as well as attrition rates. Effects were not statistically significant in assessments of secondary outcomes, possibly due to the paucity of the number of trials and patients and caregivers. Trials showed moderate to high heterogeneity which might impact the results. To better study effects on outcomes, further controlled trials are needed with rigorous attention given to improve recruitment and retention and to decrease bias. Predetermined protocols using similar measurements should be used across multiple sites.",
        "gold": "The review included 12 trials (563 people with HbSS, HbSC or HbS\u03b2thal aged six to 35 years). Participants were assigned randomly to either educational programs, no program and in some cases to a non-educational program, e.g. art therapy. Interventions ranged from a total of one hour to weekly sessions for eight weeks and post-intervention assessments ranged from the end of the intervention period to 12 months after completion. Educational programs and other interventions have resulted in improvements in patient knowledge or understanding of sickle cell disease, and a decrease in depression. Effects on patients' knowledge were maintained for longer than for caregivers. The effects are shown to be small but may result from the fact that most studies had very small numbers of participants and there was much variation between studies. The interventions studied showed no effect on patients' utilization of health services, relationships between families, caregiver or patient skills, coping or health-related quality of life of the patient. No comparative data were reported for patients or caregivers (or both) recognising signs and symptoms leading to self-management. No trials assessed the adherence to treatment. Trials varied in the interventions being studied as well as how the different outcomes were measured. The quality of evidence was low for the outcome positive coping and moderate for the outcomes child knowledge, healthcare utilization and depression. This suggests that further research is likely to have an important impact on our confidence in the effect of the treatment. Further research using randomized controlled trials with more people (including different populations) are needed to improve our understanding of which interventions are likely to be useful."
    },
    {
        "index": "cochrane-simplification-test-179",
        "sentence": "The review included six trials representing 2411 participants. Only one study included participants with both focal and generalised onset seizures; the other five trials included participants with focal onset seizures only. All six studies included adult participants between 16 and 80 years old, and treatment periods ranged from 7 to 16 weeks. We judged two studies to have low risk of bias and four to have unclear risk of bias. One study failed to provide details on the method used for allocation concealment, and one did not report all outcomes prespecified in the trial protocol. One study did not describe how blinding was maintained, and another noted discrepancies in reporting. Participants receiving brivaracetam add-on were significantly more likely to experience a 50% or greater reduction in seizure frequency than those receiving placebo (RR 1.81, 95% CI 1.53 to 2.14; 6 studies; moderate-quality evidence). Participants receiving brivaracetam were also significantly more likely to attain seizure freedom (RR 5.89, 95% CI 2.30 to 15.13; 6 studies; moderate-quality evidence). The incidence of treatment withdrawal for any reason (RR 1.27, 95% CI 0.94 to 1.74; 6 studies; low-quality evidence), as well as the risk of participants experiencing one or more adverse events (RR 1.08, 95% CI 1.00 to 1.17; 5 studies; moderate-quality evidence), was not significantly different following treatment with brivaracetam compared to placebo. However, participants receiving brivaracetam did appear to be significantly more likely to withdraw from treatment specifically because of adverse events compared with those receiving placebo (RR 1.54, 95% CI 1.02 to 2.33; 6 studies; low-quality evidence). Brivaracetam, when used as add-on therapy for patients with drug-resistant epilepsy, is effective in reducing seizure frequency and can aid patients in achieving seizure freedom. However, add-on brivaracetam is associated with a greater proportion of treatment withdrawals due to adverse events compared with placebo. It is important to note that only one of the eligible studies included participants with generalised epilepsy. None of the studies included participants under the age of 16, and all studies were of short duration. Consequently, these findings are mainly applicable to adult patients with drug-resistant focal epilepsy. Future research should thus focus on investigating the tolerability and efficacy of brivaracetam during longer-term follow-up, and should also assess the efficacy and tolerability of add-on brivaracetam in managing other types of seizures and its use in other age groups.",
        "gold": "Evidence taken from studies examining the effectiveness of brivaracetam was of moderate quality. This means that we can be fairly certain that study findings showing that brivaracetam is effective in reducing the frequency of seizures in drug-resistant epilepsy are accurate. Evidence regarding the tolerability of brivaracetam, for example, the number of people who withdrew from these studies and the number of people who experienced side effects, however, was of low quality. This means that we cannot be sure that trial findings are completely accurate, and that more research is needed to fully investigate the tolerability of brivaracetam. All study participants were adults, and most had focal epilepsy. As a result, the review cannot inform us about how effective brivaracetam is in children or in individuals with other types of epilepsy, for example, generalised epilepsy, which is epilepsy that involves the whole brain. Evidence is current to October 2018."
    },
    {
        "index": "cochrane-simplification-test-180",
        "sentence": "We included 38 studies, mostly from high-income countries, many of which explored mothers' perceptions of vaccine communication. Some focused on the MMR (measles, mumps, rubella) vaccine. In general, parents wanted more information than they were getting (high confidence in the evidence). Lack of information led to worry and regret about vaccination decisions among some parents (moderate confidence). Parents wanted balanced information about vaccination benefits and harms (high confidence), presented clearly and simply (moderate confidence) and tailored to their situation (low confidence in the evidence). Parents wanted vaccination information to be available at a wider variety of locations, including outside health services (low confidence) and in good time before each vaccination appointment (moderate confidence). Parents viewed health workers as an important source of information and had specific expectations of their interactions with them (high confidence). Poor communication and negative relationships with health workers sometimes impacted on vaccination decisions (moderate confidence). Parents generally found it difficult to know which vaccination information source to trust and challenging to find information they felt was unbiased and balanced (high confidence). The amount of information parents wanted and the sources they felt could be trusted appeared to be linked to acceptance of vaccination, with parents who were more hesitant wanting more information (low to moderate confidence). Our synthesis and comparison of the qualitative evidence shows that most of the trial interventions addressed at least one or two key aspects of communication, including the provision of information prior to the vaccination appointment and tailoring information to parents' needs. None of the interventions appeared to respond to negative media stories or address parental perceptions of health worker motives. We have high or moderate confidence in the evidence contributing to several review findings. Further research, especially in rural and low- to middle-income country settings, could strengthen evidence for the findings where we had low or very low confidence. Planners should consider the timing for making vaccination information available to parents, the settings where information is available, the provision of impartial and clear information tailored to parental needs, and parents' perceptions of health workers and the information provided.",
        "gold": "We included 38 studies in our review. Most of the studies were from high-income countries and explored mothers' perceptions of vaccine communication. Some of the studies also included the views of fathers, grandmothers and other caregivers. In general, parents wanted more information than they were getting (high confidence). For some parents, a lack of information led to worry and regret about their vaccination decision (moderate confidence). Parents wanted balanced information about both the benefits and risks of vaccination (high confidence), presented in a clear and simple manner (moderate confidence) and tailored to their situation (low confidence). Parents wanted vaccination information to be available outside of the health services (low confidence). They wanted this information in good time before each vaccination appointment and not while their child was being vaccinated (moderate confidence). Parents viewed health workers as an important source of information and had specific expectations of their interactions with them (high confidence). Poor communication and negative relationships with health workers sometimes impacted on vaccination decisions (moderate confidence). Parents generally found it difficult to know which vaccination information source to trust and found it difficult to find information that they felt was unbiased and balanced (high confidence). The amount of information parents wanted and the sources they felt they could trust seem to be linked to their acceptance of vaccination, with parents who were more hesitant wanting more information (low to moderate confidence). How up-to-date is this review? We searched for studies published before 30 August 2016."
    },
    {
        "index": "cochrane-simplification-test-181",
        "sentence": "We identified 10 trials from the search, with a total of 599 anorexia nervosa participants, and included them in the review. Seven had been identified in the previous versions of this review and we now include three new trials. We now deem one previously identified ongoing trial to be ineligible, and six ongoing trials are new for this update. Two of the 10 trials included children. Trials tested diverse psychological therapies and comparability was poor. Risks of bias were mostly evident through lack of blinded outcome assessments (in 60% of studies) and incomplete data reporting (attrition bias). The results suggest that treatment as usual (TAU) when delivered by a non-eating-disorder specialist or similar may be less efficacious than focal psychodynamic therapy. This was suggested for a primary outcome of recovery by achievement of a good or intermediate outcome on the Morgan and Russell Scale (RR 0.70, 95% confidence interval (CI) 0.51 to 0.97; 1 RCT, 40 participants; very low-quality evidence). However there were no differences between cognitive analytic therapy and TAU for this outcome (RR 0.78, 95% CI 0.61 to 1.00; 2 RCTs, 71 participants; very low-quality evidence), nor for body mass index (BMI). There were no differences in overall dropout rates between individual psychological therapies and TAU. Two trials found a non-specific specialist therapy (Specialist Supportive Clinical Management) or an Optimised TAU delivered by therapists with eating disorder expertise was similar in outcomes to cognitive behaviour therapy (BMI MD -0.00, 95% CI -0.91 to 0.91; 197 participants, low-quality evidence). When comparing individual psychological therapies with each other, no specific treatment was consistently superior to any other specific approach. Dietary advice as a control arm had a 100% non-completion rate in one trial (35 participants). None of the trials identified any adverse effects. Insufficient power was problematic for the majority of trials. There was a suggestion in one trial that focal psychodynamic therapy might be superior to TAU, but this is in the context of TAU performing poorly. An alternative control condition of dietary advice alone appeared to be unacceptable, but again this is based on just one trial. Owing to the risk of bias and limitations of studies, notably small sample sizes, we can draw no specific conclusions about the effects of specific individual psychological therapies for anorexia nervosa in adults or older adolescents. Larger RCTs of longer treatment duration and follow-up are needed.",
        "gold": "There was a limited amount of very low-quality evidence to suggest that people might do better when receiving focal psychodynamic therapy compared to no treatment or treatment as usual. With one exception, we found little difference between specific psychological therapies. Most therapies appeared as acceptable as any other approach, except for dietary advice which had a 100% non-completion rate in one small trial. Because of the risk of bias and limitations of studies, notably small sample sizes, we can draw no specific conclusions about the effects of specific individual psychological therapies for anorexia nervosa in adults or older adolescents. We need more large multicentre randomised controlled trials of commonly-used psychological therapies in older adolescents and adults with anorexia nervosa."
    },
    {
        "index": "cochrane-simplification-test-182",
        "sentence": "The review included 516 participants from three RCTs. One study was conducted in the USA and consisted of two trials: the first trial randomized 151 adults to receive either silicone oil or sulfur hexafluoride (SF6) gas tamponades; and the second trial randomized 271 adults to receive either silicone oil or perfluropropane (C3F8) gas tamponades. The third trial was a multi-center international trial and randomized 94 participants (age range not specified) to receive heavy silicone oil (a mixture of perfluorohexyloctane (F6H8) and silicone oil) versus standard silicone oil (either 1000 centistokes or 5000 centistokes, per the surgeon's preference). In participants with RD associated with PVR, outcomes after pars plana vitrectomy and infusion of either silicone oil, perfluropropane gas, or sulfur hexafluoride gas appeared comparable for a broad variety of cases. There were no significant differences between silicone oil and perfluoropropane gas in terms of the proportion of participants achieving at least 5/200 visual acuity (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.73 to 1.31) or achieving macular attachment (RR 1.00; 95% CI 0.86 to 1.15) at a minimum of one year. Although sulfur hexafluoride gas was reported to be associated with significantly worse anatomic and visual outcomes than was silicone oil at one year (quantitative data not reported), there were no significant differences between silicone oil and sulfur hexafluoride gas in terms of achieving at least 5/200 visual acuity at two years (RR 1.57; 95% CI 0.93 to 2.66). For macular attachment, participants treated with silicone oil received significantly more favourable outcomes than did participants who received sulfur hexafluoride at both one year (quantitative data not reported) and two years (RR 1.37; 95% CI 1.01 to 1.86). The first two trials did not perform any sample size calculation or power detection. In the third trial, which had a power of 80% to detect differences, heavy silicone oil was not shown to be superior to standard silicone oil. There were no significant differences between standard silicone oil and heavy silicone oil in the change in visual acuity at one year using adjusted mean logMAR visual acuity (mean difference -0.03 logMAR; 95% CI -0.35 to 0.29). Adverse events were not reported for the first two trials. For the third trial, only the total number of adverse events was reported, and adverse events for each group were not specified. Of the 94 participants, four died, 26 had recurrent retinal detachment, 22 developed glaucoma, four developed a cataract, and two had capsular fibrosis. All three trials employed adequate methods for random sequence generation and allocation concealment. None of the trials employed masking of participants and surgeons, and only the third trial masked outcome assessors. The first trial had a large portion of participants excluded from the final analyses, while the other two trials were at low risk of attrition bias. All trials appear to be free of reporting bias. The first two trials were funded by the National Eye Institute, and the third trial was funded by the German Research Foundation. The use of either perfluropropane or standard silicone oil appears reasonable for most patients with RD associated with PVR. Because there do not appear to be any major differences in outcomes between the two agents, the choice of a tamponade agent should be individualized for each patient. Heavy silicone oil, which is not available for routine clinical use in the USA, has not demonstrated evidence of superiority over standard silicone oil.",
        "gold": "We found three randomized controlled trials (RCTs) involving 516 participants that compared tamponade agents. All participants underwent surgery to treat RD associated with PVR. The Silicone Study compared the use of silicone oil to either sulfur hexafluoride (SF6) gas or perfluropropane (C3F8) gas in two RCTs. Both gases and silicone oil are less dense than water, so that they float upwards or towards the top of the eye while a patient is sitting or standing. This is sometimes but not always beneficial, so a denser-than-water silicone oil called heavy silicone oil has been investigated, primarily outside the US. The Heavy Silicone Oil Study compared the use of heavy silicone oil to standard silicone oil in participants with RD involving the lower parts of the retina. The evidence was current to June 2013. When silicone oil was compared to SF6 gas, eyes randomized to receive silicone oil more often achieved a visual acuity of 5/200 or better at one year, and more often achieved macular attachment at one year but with no difference at two years. When silicone oil was compared with C3F8 gas, there were no significant differences between the groups with respect to visual acuity or macular attachment at one year. When heavy silicone oil was compared to standard silicone oil, there were no significant differences between the groups with respect to retinal re-attachment or visual acuity at one year. Heavy silicone oil did not demonstrate any significant benefit over standard silicone oil. Adverse events were only reported for the Heavy Silicone Oil Study; however, only the total number of adverse events was reported, and the numbers for each group were not specified: of the 94 participants, there were four deaths, 26 recurrent RDs, 22 patients with glaucoma, four patients with cataract, and two patients with capsular fibrosis (scarring behind a lens implant). The overall quality of these studies was moderately satisfactory. Although all trials employed proper randomization methods for participants, the masking of participants was unclear in all of the three RCTs, and masking of outcome assessors was not performed in two RCTs."
    },
    {
        "index": "cochrane-simplification-test-183",
        "sentence": "We included five studies (involving 1819 women) in this review. There was a lower risk of composite maternal mortality and severe morbidity for women randomised to receive planned early delivery (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83, two studies, 1459 women (evidence graded high)). There were no clear differences between subgroups based on our subgroup analysis by gestational age, gestational week or condition. Planned early delivery was associated with lower risk of HELLP syndrome (RR 0.40, 95% CI 0.17 to 0.93, 1628 women; three studies) and severe renal impairment (RR 0.36, 95% CI 0.14 to 0.92, 100 women, one study). There was not enough information to draw any conclusions about the effects on composite infant mortality and severe morbidity. We observed a high level of heterogeneity between the two studies in this analysis (two studies, 1459 infants, I2 = 87%, Tau2 = 0.98), so we did not pool data in meta-analysis. There were no clear differences between subgroups based on our subgroup analysis by gestational age, gestational week or condition. Planned early delivery was associated with higher levels of respiratory distress syndrome (RR 2.24, 95% CI 1.20 to 4.18, three studies, 1511 infants), and NICU admission (RR 1.65, 95% CI 1.13 to 2.40, four studies, 1585 infants). There was no clear difference between groups for caesarean section (RR 0.91, 95% CI 0.78 to 1.07, 1728 women, four studies, evidence graded moderate), or in the duration of hospital stay for the mother after delivery of the baby (mean difference (MD) -0.16 days, 95% CI -0.46 to 0.15, two studies, 925 women, evidence graded moderate) or for the baby (MD -0.20 days, 95% CI -0.57 to 0.17, one study, 756 infants, evidence graded moderate). Two fairly large, well-designed trials with overall low risk of bias contributed the majority of the evidence. Other studies were at low or unclear risk of bias. No studies attempted to blind participants or clinicians to group allocation, potentially introducing bias as women and staff would have been aware of the intervention and this may have affected aspects of care and decision-making. The level of evidence was graded high (composite maternal mortality and morbidity), moderate (caesarean section, duration of hospital stay after delivery for mother, and duration of hospital stay after delivery for baby) or low (composite infant mortality and morbidity). Where the evidence was downgraded, it was mostly because the confidence intervals were wide, crossing both the line of no effect and appreciable benefit or harm. For women suffering from hypertensive disorders of pregnancy after 34 weeks, planned early delivery is associated with less composite maternal morbidity and mortality. There is no clear difference in the composite outcome of infant mortality and severe morbidity; however, this is based on limited data (from two trials) assessing all hypertensive disorders as one group. Further studies are needed to look at the different types of hypertensive diseases and the optimal timing of delivery for these conditions. These studies should also include infant and maternal morbidity and mortality outcomes, caesarean section, duration of hospital stay after delivery for mother and duration of hospital stay after delivery for baby. An individual patient meta-analysis on the data currently available would provide further information on the outcomes of the different types of hypertensive disease encountered in pregnancy.",
        "gold": "We searched for evidence on 12 January 2016 and found five randomised studies, involving 1819 women. Two of the studies were large, high-quality studies, in women with gestational hypertension, mild pre-eclampsia or deteriorating existing hypertension at 34 to 37 weeks (704 women) or with gestational hypertension or mild pre-eclampsia at 36 to 41 weeks (756 women). Fewer women who received planned early delivery experienced severe adverse outcomes (1459 women, high-quality evidence). There was not enough information to draw any conclusions about the effects on the number of babies born with poor health, with a high level of variability between the two studies (1459 infants, low-quality evidence). There was no clear difference between planned early delivery and delayed delivery for the number of caesarean sections (four studies, 1728 women, moderate-quality evidence), or the duration of the mother\u2019s hospital stay after the birth of the baby (two studies, 925 women, moderate-quality evidence) (or for the baby (one study, 756 infants, moderate-quality evidence)). More babies who were delivered early had breathing problems (respiratory distress syndrome, three studies, 1511 infants), or were admitted to the neonatal unit (four studies, 1585 infants). Fewer women who delivered early developed HELLP syndrome (three studies, 1628 women) or severe kidney problems (one study, 100 women). Two studies compared women who had labour induced at 34 to 36 weeks and at 34 to 37 weeks with a comparison group who were monitored until 37 weeks, when induction was begun if labour had not started spontaneously. Three studies compared induction of labour at term or closer to term, at 37 completed weeks and at 36 to 41 weeks, with women who were monitored until 41 weeks when induction was begun if labour had not started spontaneously. Other inclusion and exclusion criteria also differed between the five studies. No studies attempted to blind the women or their clinicians to which group they were in. Women and staff were aware of the intervention and this may have affected aspects of care and decision-making. Most of the evidence was of moderate quality, so we can be moderately certain about the findings. Overall, if a woman\u2019s baby was delivered immediately after 34 weeks, there was less risk of a complication for the mother and no clear difference in the overall rate of complications for the baby, but information was limited. These findings are applicable to general obstetric practice when high blood pressure disorders during pregnancy are considered together. Further studies are needed to look at the different types of hypertensive disorders individually."
    },
    {
        "index": "cochrane-simplification-test-184",
        "sentence": "Six studies (including 142 participants) were eligible for inclusion. Two compared three-times-a-week prophylactic administration with on-demand treatment in children with hemophilia. Pooled results from these two studies showed a rate ratio of 0.30 (95% confidence interval; 0.12 to 0.76) for all bleedings and 0.22 (95% confidence interval 0.08 to 0.63) for joint bleedings favouring prophylaxis. Results on the number of patients with preserved joints after three to seven years of follow-up were not pooled due to significant heterogeneity. Three of the remaining four studies evaluated hemophilia A; one showed a statistically significant decrease in frequency of joint bleeds with prophylaxis compared to placebo, with a rate difference of -10.73 (95% confidence interval -16.55 to -4.91) bleeds per year. Two studies compared two prophylaxis regimens, failing to demonstrate an advantage of one regimen over the other in terms of bleeding frequency. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, rate difference -3.30 (95% confidence interval -5.50 to -1.10) bleeds per year. Non-significant increases in both inhibitor and infectious complications were observed in patients on prophylaxis, which occurred more often when using long-term venous access. There is strong evidence from randomised controlled trials and observational trials that prophylaxis preserves joint function in children with hemophilia as compared to on-demand treatment. There is insufficient evidence from randomised controlled trials to confirm the observational evidence that prophylaxis decreases bleeding and related complications in patients with existing joint damage. Well-designed randomised controlled trials and prospective observational controlled studies are needed to establish the best prophylactic regimen and to assess the effectiveness of prophylactic clotting factor concentrates in adult patients.",
        "gold": "This review includes six randomised controlled trials. Two compare the regular use of clotting factor concentrates to prevent joint bleeds with their use 'on demand'. Four compare different regimens of regular use in children and adults with hemophilia. It was clearly evident that preventative therapy, as intravenous infusion of factor concentrate repeated more times a week and started early in childhood was able to reduce joint deterioration as compared to treatment administered after bleeding occurred. This favourable effect is due to a consistent reduction in total bleeds and hemarthrosis (bleeding into joints) and leads to a significant improvement in quality of life. Preventative therapy is linked to an increased factor usage and cost of treatment. We found weaker evidence (due to lack of data) to show preventative therapy reduced joint deterioration when treatment is started after joint damage has been established. Further studies are needed to establish the best preventative regimen, i.e. for example starting time, dosage frequency, minimally effective dose."
    },
    {
        "index": "cochrane-simplification-test-185",
        "sentence": "We included one new study in this update. In total, 13 trials involving 1824 participants met the inclusion criteria for this review however, data in usable format were only available in 10 trials (732 participants). Inadequate reporting of study methodology was a common feature of the trials preventing thorough assessment of study quality. We were unable to pool data for any of the outcomes due to the differences between the interventions assessed in the studies. Eight studies aimed to induce remission; overall survival did not differ significantly between treatment groups. Five studies aimed to maintain remission. In two out of three studies reporting survival, this was substantial but the difference was not statistically significant between treatment groups. Less aggressive treatment schedules appear to produce similar effects with less adverse event profiles. This review notes a preference in more recent studies for less aggressive care options for treatment of BL. However, the evidence for the relative effectiveness of interventions to treat BL is not strong as studies were small, underpowered and prone to both systematic and random error. We included one additional trial without change of conclusions.",
        "gold": "This review aims to evaluate these treatments to assess their effectiveness especially for later stages. The review identified 13 trials involving 1824 participants. However, data presentable for the review were only available in 10 trials with 732 participants. The data were difficult to collate because of the quality of the study methods and the reporting of the results; outcome measures differed between trials and they were mainly small-sized trials. No significant differences in overall survival were seen between studies aimed at inducing remission. Adverse events reported were mostly due to infections and reductions in blood cell counts. The more recent studies were focused on using less intensive treatment regimens as they could provide similar responses with lower risk of adverse effects."
    },
    {
        "index": "cochrane-simplification-test-186",
        "sentence": "Two studies involving 447 (with sample sizes 14 and 432) RhD negative women were included. The studies compared IM and IV administration of anti-D prophylaxis. In both studies the women received a 1500 IU (300 microgram) dose of Rhophylac during week 28 of gestation. There was no incidence of RhD alloimmunization in either of the studies, as the sample size was insufficient for meaningful comparison of this uncommon outcome. One of the studies found that the mean anti-D IgG concentrations after IV and IM administration differed up to seven days (36.1 (2.6) ng/mL IV; 19.8 (8.7) ng/mL IM on day seven). However, from two to three weeks post-administration, the concentrations were similar for both routes of administration. None of the women involved in the studies developed antibodies against the RhD antigen. It appears that IM and IV administration of anti-D are equally effective. The number of included studies and the number of participants are not enough to assess whether there are any differences. Anti-D can be administered by IM or IV injection. The choice of IM or IV route of administration will depend on the available preparations, the dose to be administered and also on the patients' preferences. This review found insufficient information upon which to guide practice due to the limited number of included studies, small sample sizes and methodological limitations.",
        "gold": "We identified two completed randomized controlled studies, involving 447 RhD-negative women. The findings suggest that intramuscular and intravenous anti-D in the 28th week of pregnancy are equally effective in preventing RhD antibody formation (alloimmunization) during the pregnancy. None of the women developed antibodies against the RhD antigen. The small number of studies, low number of participants and methodological limitations mean that we do not have sufficient information to guide practice. The choice of intramuscular or intravenous route of administration will depend on available preparations, the dose to be administered and the woman's preference."
    },
    {
        "index": "cochrane-simplification-test-187",
        "sentence": "Eight studies with a total of 21,379 patients with diabetes were included. Three included studies investigated ticlopidine compared to aspirin or placebo. Five included studies investigated clopidogrel compared to aspirin or a combination of aspirin and dipyridamole, or compared clopidogrel in combination with aspirin to aspirin alone. All trials included patients with previous CVD except the CHARISMA trial which included patients with multiple risk factors for coronary artery disease. Overall the risk of bias of the trials was low. The mean duration of follow-up ranged from 365 days to 913 days. Data for diabetes patients on all-cause mortality, vascular mortality and myocardial infarction were only available for one trial (355 patients). This trial compared ticlopidine to placebo and did not demonstrate any statistically significant differences for all-cause mortality, vascular mortality or myocardial infarction. Diabetes outcome data for stroke were available in three trials (31% of total diabetes participants). Overall pooling of two (statistically heterogeneous) studies showed no statistically significant reduction in the combination of fatal and non-fatal stroke (359/3194 (11.2%) versus 356/3146 (11.3%), random effects odds ratio (OR) 0.81; 95% confidence interval (CI) 0.44 to 1.49) for ADP receptor antagonists versus other antiplatelet drugs. There were no data available from any of the trials on peripheral vascular disease, health-related quality of life, adverse events specifically for patients with diabetes, or costs. The available evidence for ADP receptor antagonists in patients with diabetes mellitus is limited and most trials do not report outcomes for patients with diabetes separately. Therefore, recommendations for the use of ADP receptor antagonists for the prevention of CVD in patients with diabetes are based on available evidence from trials including patients with and without diabetes. Trials with diabetes patients and subgroup analyses of patients with diabetes in trials with combined populations are needed to provide a more robust evidence base to guide clinical management in patients with diabetes.",
        "gold": "This review assessed if these medications would be useful in patients with diabetes. We included eight trials with 21,379 patients and a mean duration of follow-up ranging from 365 to 913 days. Specific data for patients with diabetes were only available in full for one of these trials and partial data were available for two trials. Analysis of the available data demonstrated that adenosine-diphosphate receptor antagonists (such as clopidogrel, prasugrel, ticagrelor, ticlopidine) were not more effective than other blood thinning drugs or placebo for death from any cause, death related to cardiovascular disease, heart attacks or strokes. There was no available information on the effects of adenosine-diphosphate receptor antagonists on health-related quality of life, adverse effects specially for people with diabetes, or costs. The use of adenosine-diphosphate receptor antagonists in patients with diabetes needs to be guided by the information available from trials which included patients with and without diabetes. All future trials on adenosine-diphosphate receptor antagonists should include data which relate specifically to patients with diabetes in order to inform evidence-based clinical guidelines."
    },
    {
        "index": "cochrane-simplification-test-188",
        "sentence": "Ten trials met the inclusion criteria with a total of 191 participants. Seven trials evaluated single treatment sessions, one evaluated a two-week intervention, one evaluated a six-week intervention and one a three-month intervention. It is only possible to blind trials of airway clearance and overnight ventilatory support to the outcome assessors. In most of the trials we judged there was an unclear risk of bias with regards to blinding due to inadequate descriptions. The six-week trial was the only one judged to have a low risk of bias for all other domains. One single intervention trial had a low risk of bias for the randomisation procedure with the remaining trials judged to have an unclear risk of bias. Most trials had a low risk of bias with regard to incomplete outcome data and selective reporting. Six trials (151 participants) evaluated non-invasive ventilation for airway clearance compared with an alternative chest physiotherapy method such as the active cycle of breathing techniques or positive expiratory pressure. Three trials used nasal masks, one used a nasal mask or mouthpiece and one trial used a face mask and in one trial it is unclear. Three of the trials reported on one of the review's primary outcome measures (quality of life). Results for the reviews secondary outcomes showed that airway clearance may be easier with non-invasive ventilation and people with cystic fibrosis may prefer it. We were unable to find any evidence that non-invasive ventilation increases sputum expectoration, but it did improve some lung function parameters. Three trials (27 participants) evaluated non-invasive ventilation for overnight ventilatory support compared to oxygen or room air using nasal masks (two trials) and nasal masks or full face masks (one trial). Trials reported on two of the review's primary outcomes (quality of life and symptoms of sleep-disordered breathing). Results for the reviews secondary outcome measures showed that they measured lung function, gas exchange, adherence to treatment and preference, and nocturnal transcutaneous carbon dioxide. Due to the small numbers of participants and statistical issues, there were discrepancies in the results between the RevMan and the original trial analyses. No clear differences were found between non-invasive ventilation compared with oxygen or room air except for exercise performance, which significantly improved with non-invasive ventilation compared to room air over six weeks. One trial (13 participants) evaluated non-invasive ventilation on exercise capacity (interface used was unclear) and did not reported on any of the review's primary outcomes. The trial found no clear differences between non-invasive ventilation compared to no non-invasive ventilation for any of our outcomes. Three trials reported on adverse effects. One trial, evaluating non-invasive ventilation for airway clearance, reported that a participant withdrew at the start of the trial due to pain on respiratory muscle testing. One trial evaluating non-invasive ventilation for overnight support reported that one participant could not tolerate an increase in inspiratory positive airway pressure. A second trial evaluating non-invasive ventilation in this setting reported that one participant did not tolerate the non-invasive ventilation mask, one participant developed a pneumothorax when breathing room air and two participants experienced aerophagia which resolved when inspiratory positive airway pressure was decreased. Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum. Non-invasive ventilation, used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. The effect of NIV on exercise is unclear. These benefits of non-invasive ventilation have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in cystic fibrosis airway clearance and exercise.",
        "gold": "This review includes 10 trials (191 people with cystic fibrosis) - seven single-treatment sessions and a two-week trial, a six-week trial and a three-month trial. Six single-treatment trials, the two-week trial and the three-month trial compared non-invasive ventilation with other airway clearance techniques. Two single-treatment trials and the six-week trial looked at non-invasive ventilation for overnight breathing support compared to oxygen or normal room air. One single-treatment trial compared non-invasive ventilation with no additional treatment during an exercise test. Single-treatment trials of non-invasive ventilation for airway clearance showed that this may be easier with non-invasive ventilation and people with cystic fibrosis may prefer it to other methods. We could not find evidence that non-invasive ventilation increased the amount of mucus coughed up, but it did improve some measures of lung function, at least in the short term. The two-week trial did not demonstrate clear benefits between groups. The original three-month trial report stated an improvement in lung clearance index. One person in one of these trials reported pain on respiratory muscle testing. The three trials comparing overnight support from non-invasive ventilation measured lung function, quality of life and carbon dioxide levels; they showed it is effective, safe and acceptable. We found no clear differences between non-invasive ventilation and oxygen or room air, except for exercise performance which improved with non-invasive ventilation compared to room air after six weeks. Two trials reported side effects. In the first trial, one person found the mask uncomfortable. In the second trial, one person in the room air group had collapsed lungs and two people could not tolerate increased pressure when breathing in. The trial comparing the effects of non-invasive ventilation to no treatment on exercise capacity found no clear differences between groups. Non-invasive ventilation may help alongside other airway clearance techniques, particularly when people with cystic fibrosis have difficulty coughing up mucus and during sleep. Long-term trials are needed with enough people to show the clinical effects of non-invasive ventilation on airway clearance, during sleep and exercise training in severe disease. The benefits of non-invasive ventilation have largely been demonstrated in single-treatment sessions with only small numbers of people. There is limited evidence of some longer-term improvement in lung function in one trial. Our results from the trials of overnight breathing support differed from those in the original analyses, this is likely due to the small numbers of participants and some statistical issues. We judged only the six-week trial to be free from any bias. In the remaining trials, we thought there were low or unclear chances of the results being affected because data were either reported only partially or not at all. We were not sure if the way in which participants were put into the different treatment groups would affect the results of the trials."
    },
    {
        "index": "cochrane-simplification-test-189",
        "sentence": "This update of the systematic review on nocturnal-NIPPV in COPD (Wijkstra 2002), has led to the inclusion of three new studies, leading to seven included studies on 245 people. We obtained IPD for all participants in all included studies. The 95% confidence interval (CI) of all outcomes included zero. These included partial pressure of CO2 and O2 in arterial blood, six-minute walking distance (6MWD), health-related quality of life (HRQoL), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), maximal inspiratory pressure (PImax) and sleep efficiency. The mean effect on 6MWD was small at 27.7 m and not statistically significant. Given the width of the 95% CI (-28.1 to 66.3 m), the real effect of NIPPV on 6MWD is uncertain and we cannot exclude an effect that is clinically significant (considering that the minimal clinically difference on 6MWD is around 26 m). Nocturnal-NIPPV at home for at least three months in hypercapnic patients with stable COPD had no consistent clinically or statistically significant effect on gas exchange, exercise tolerance, HRQoL, lung function, respiratory muscle strength or sleep efficiency. Meta-analysis of the two new long-term studies did not show significant improvements in blood gases, HRQoL or lung function after 12 months of NIPPV. However, the small sample sizes of these studies preclude a definite conclusion regarding the effects of NIPPV in COPD.",
        "gold": "The evidence is current to August 2012. We found seven studies that reported the effects of NIPPV at home. Five of these studies looked at the effects after using NIPPV compared to regular treatment (without NIPPV) for at least three months. Two studies looked for a longer period of time, for at least 12 months. The mean age of all participants included in our meta-analysis was 67 years. All studies included men and women, but 77% of participants were men. We used data from 245 people for our meta-analysis. NIPPV during the night for 3 and 12 months in people with COPD who had raised levels of carbon dioxide had no clinically or statistically significant effect on gas exchange, six-minute walking distance, health-related quality of life, lung function, respiratory muscle strength and sleep efficiency. This means we found little or no difference in the outcomes. Because some trials had very small numbers of participants, our confidence in the quality of evidence is moderate when looking at the effects on gas exchange. All seven trials measured this outcome. Other outcomes were not always measured or available leading to a lower quality of evidence for the other outcomes such as six-minute walking distance, health-related quality of life, lung function, respiratory muscle function and sleep efficiency."
    },
    {
        "index": "cochrane-simplification-test-190",
        "sentence": "We included four trials, involving 1190 women. It was not possible to blind women and staff to the intervention, but for other 'Risk of bias' domains these studies were assessed as being at low or unclear risk of bias. Compared to expectant management, there was no clear effect of induction of labour for suspected macrosomia on the risk of caesarean section (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.76 to 1.09; 1190 women; four trials, moderate-quality evidence) or instrumental delivery (RR 0.86, 95% CI 0.65 to 1.13; 1190 women; four trials, low-quality evidence). Shoulder dystocia (RR 0.60, 95% CI 0.37 to 0.98; 1190 women; four trials, moderate-quality evidence), and fracture (any) (RR 0.20, 95% CI 0.05 to 0.79; 1190 women; four studies, high-quality evidence) were reduced in the induction of labour group. There were no clear differences between groups for brachial plexus injury (two events were reported in the control group in one trial, low-quality evidence). There was no strong evidence of any difference between groups for measures of neonatal asphyxia; low five-minute infant Apgar scores (less than seven) or low arterial cord blood pH (RR 1.51, 95% CI 0.25 to 9.02; 858 infants; two trials, low-quality evidence; and, RR 1.01, 95% CI 0.46 to 2.22; 818 infants; one trial, moderate-quality evidence, respectively). Mean birthweight was lower in the induction group, but there was considerable heterogeneity between studies for this outcome (mean difference (MD) -178.03 g, 95% CI -315.26 to -40.81; 1190 infants; four studies; I2 = 89%). In one study with data for 818 women, third- and fourth-degree perineal tears were increased in the induction group (RR 3.70, 95% CI 1.04 to 13.17). For outcomes assessed using GRADE, we based our downgrading decisions on high risk of bias from lack of blinding and imprecision of effect estimates. Induction of labour for suspected fetal macrosomia has not been shown to alter the risk of brachial plexus injury, but the power of the included studies to show a difference for such a rare event is limited. Also antenatal estimates of fetal weight are often inaccurate so many women may be worried unnecessarily, and many inductions may not be needed. Nevertheless, induction of labour for suspected fetal macrosomia results in a lower mean birthweight, and fewer birth fractures and shoulder dystocia. The unexpected observation in the induction group of increased perineal damage, and the plausible, but of uncertain significance, observation of increased use of phototherapy, both in the largest trial, should also be kept in mind. Findings from trials included in the review suggest that to prevent one fracture it would be necessary to induce labour in 60 women. Since induction of labour does not appear to alter the rate of caesarean delivery or instrumental delivery, it is likely to be popular with many women. In settings where obstetricians can be reasonably confident about their scan assessment of fetal weight, the advantages and disadvantages of induction at or near term for fetuses suspected of being macrosomic should be discussed with parents. Although some parents and doctors may feel the evidence already justifies induction, others may justifiably disagree. Further trials of induction shortly before term for suspected fetal macrosomia are needed. Such trials should concentrate on refining the optimum gestation of induction, and improving the accuracy of the diagnosis of macrosomia.",
        "gold": "We found four trials that assessed induction of labour at 37 to 40 weeks for women when it was suspected that their baby was large. A total of 1190 pregnant, non-diabetic women were involved. We searched for evidence on 31 October 2015. The studies were of moderate or good quality although it was not possible to blind the women and staff providing care to which group women had been assigned. This may have introduced bias. The number of births where the baby's shoulder became stuck (shoulder dystocia) or a bone was fractured (usually the clavicle, which heals well without consequences) were reduced in the induction of labour group. The evidence was assessed as moderate quality for shoulder dystocia and high quality for fracture. No clear differences between groups were reported for damage to the network of nerves that send signals from the spine to the shoulder, arm and hand (brachial plexus injury) of the baby (low-quality evidence due to very few events occurring) or signs of not enough oxygen during birth. A policy of labour induction reduced the average birthweight of babies by 178 g. The trials did not show any differences in the number of women who had caesarean sections or instrumental births. There is limited evidence that more women in the induction of labour group had severe damage to the perineum. We conclude that there appear to be benefits, but there may also be some disadvantages of induction of labour shortly before term. The option of having an induction should be discussed with parents when their baby is suspected to be extra large. Although some parents and doctors may feel the existing evidence is sufficient to justify inducing labour, others may disagree. Further high-quality studies are needed in order to find out what is the best time to induce labour towards the end of pregnancy, and how to improve the accuracy in diagnosing macrosomia. A visual summary of some of the results from this review can be found here (screen view version) and (printable version here)."
    },
    {
        "index": "cochrane-simplification-test-191",
        "sentence": "We identified 159 randomised clinical trials. Ninety-four trials reported no mortality, and nine trials reported mortality but did not report in which intervention group the mortality occurred. Accordingly, 56 randomised trials with 95,286 participants provided usable data on mortality. The age of participants ranged from 18 to 107 years. Most trials included women older than 70 years. The mean proportion of women was 77%. Forty-eight of the trials randomly assigned 94,491 healthy participants. Of these, four trials included healthy volunteers, nine trials included postmenopausal women and 35 trials included older people living on their own or in institutional care. The remaining eight trials randomly assigned 795 participants with neurological, cardiovascular, respiratory or rheumatoid diseases. Vitamin D was administered for a weighted mean of 4.4 years. More than half of the trials had a low risk of bias. All trials were conducted in high-income countries. Forty-five trials (80%) reported the baseline vitamin D status of participants based on serum 25-hydroxyvitamin D levels. Participants in 19 trials had vitamin D adequacy (at or above 20 ng/mL). Participants in the remaining 26 trials had vitamin D insufficiency (less than 20 ng/mL). Vitamin D decreased mortality in all 56 trials analysed together (5,920/47,472 (12.5%) vs 6,077/47,814 (12.7%); RR 0.97 (95% confidence interval (CI) 0.94 to 0.99); P = 0.02; I2 = 0%). More than 8% of participants dropped out. 'Worst-best case' and 'best-worst case' scenario analyses demonstrated that vitamin D could be associated with a dramatic increase or decrease in mortality. When different forms of vitamin D were assessed in separate analyses, only vitamin D3 decreased mortality (4,153/37,817 (11.0%) vs 4,340/38,110 (11.4%); RR 0.94 (95% CI 0.91 to 0.98); P = 0.002; I2 = 0%; 75,927 participants; 38 trials). Vitamin D2, alfacalcidol and calcitriol did not significantly affect mortality. A subgroup analysis of trials at high risk of bias suggested that vitamin D2 may even increase mortality, but this finding could be due to random errors. Trial sequential analysis supported our finding regarding vitamin D3, with the cumulative Z-score breaking the trial sequential monitoring boundary for benefit, corresponding to 150 people treated over five years to prevent one additional death. We did not observe any statistically significant differences in the effect of vitamin D on mortality in subgroup analyses of trials at low risk of bias compared with trials at high risk of bias; of trials using placebo compared with trials using no intervention in the control group; of trials with no risk of industry bias compared with trials with risk of industry bias; of trials assessing primary prevention compared with trials assessing secondary prevention; of trials including participants with vitamin D level below 20 ng/mL at entry compared with trials including participants with vitamin D levels equal to or greater than 20 ng/mL at entry; of trials including ambulatory participants compared with trials including institutionalised participants; of trials using concomitant calcium supplementation compared with trials without calcium; of trials using a dose below 800 IU per day compared with trials using doses above 800 IU per day; and of trials including only women compared with trials including both sexes or only men. Vitamin D3 statistically significantly decreased cancer mortality (RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I2 = 0%; 44,492 participants; 4 trials). Vitamin D3 combined with calcium increased the risk of nephrolithiasis (RR 1.17 (95% CI 1.02 to 1.34); P = 0.02; I2 = 0%; 42,876 participants; 4 trials). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18 (95% CI 1.17 to 8.68); P = 0.02; I2 = 17%; 710 participants; 3 trials). Vitamin D3 seemed to decrease mortality in elderly people living independently or in institutional care. Vitamin D2, alfacalcidol and calcitriol had no statistically significant beneficial effects on mortality. Vitamin D3 combined with calcium increased nephrolithiasis. Both alfacalcidol and calcitriol increased hypercalcaemia. Because of risks of attrition bias originating from substantial dropout of participants and of outcome reporting bias due to a number of trials not reporting on mortality, as well as a number of other weaknesses in our evidence, further placebo-controlled randomised trials seem warranted.",
        "gold": "In the 56 trials that provided data for the analyses, a total of 95,286 participants were randomly assigned to vitamin D versus no treatment or placebo. More than half of the trials were considered to have low risk of bias. All trials were conducted in high-income countries. The age of participants ranged from 18 to 107 years. The mean proportion of women was 77%. Vitamin D was administered for an average of 4.4 years. This plain language summary is as current as of February 2012. This review suggests that vitamin D3 may reduce mortality, showing that about 150 participants need to be treated over five years for one additional life to be saved. We found comparable effects of vitamin D3 in studies that included only women compared with studies including both women and men. Vitamin D3 also seemed to decrease cancer mortality, showing a reduction in mortality of 4 per 1000 persons treated for five to seven years. We also observed adverse effects to vitamin D such as renal stone formation (seen for vitamin D3 combined with calcium) and elevated blood levels of calcium (seen for both alfacalcidol and calcitriol). In conclusion, we found some evidence that vitamin D3 seems to decrease mortality in elderly people not dependent on help or living in institutional care. A large number of study participants left the trial before completion, and this raises concerns regarding the validity of the results. More randomised clinical trials are needed on the effects of vitamin D3 on mortality in younger, healthy persons, as well as in elderly community-dwelling and institutionalised persons without apparent vitamin D deficiency."
    },
    {
        "index": "cochrane-simplification-test-192",
        "sentence": "A sufficient number of studies were available for a quantitative synthesis for fluoxetine, orlistat, and sibutramine. Twenty two randomized controlled trials were included in the review, with a total of 296 participants for fluoxitine, 2036 for orlistat, and 1047 for sibutramine. Pharmacotherapy produced modest reductions in weight for fluoxetine (5.1 kg (95% confidence interval [CI], 3.3 - 6.9) at 24 to 26 weeks follow up; orlistat 2.0 kg (CI, 1.3 - 2.8) at 12 to 57 weeks follow-up, and sibutramine 5.1 kg (CI, 3.2 - 7.0) at 12 to 52 weeks follow-up. Glycated hemoglobin also modestly and significantly reduced for fluoxetine and orlistat. Gastrointestinal side effects were common with orlistat; tremor, somnolence and sweating with fluoxetine; and palpitations with sibutramine. Some studies, using a variety of study designs, were available on other drugs and a significant decrease in weight was noted in three studies of mazindol, one of phenmetrazine, two of phentermine. No studies were identified that fit inclusion criteria for pseudoephedrine, ephedra, sertraline, yohimbine, amphetamine or its derivatives, bupropion, topiramate, benzocaine, threachlorocitric acid, sertraline, and bromocriptine. Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes.",
        "gold": "This review of drugs for weight loss among adults with type 2 diabetes revealed weight loss of between 2.0 and 5.1 kg for fluoxetine, orlistat and sibutramine at follow-up of up to 57 weeks. The long-term effects remain uncertain. Adverse events were common in all three drugs: gastrointestinal side effects with orlistat; tremor, somnolence, and sweating with fluoxetine; and palpitations with sibutramine. There were few studies examining other drugs used for weight loss in populations with diabetes."
    },
    {
        "index": "cochrane-simplification-test-193",
        "sentence": "Five studies involving a total of 734 participants were eligible for inclusion. We assessed only one study as good quality and the other four as poor quality. However, it was difficult to perform a meta-analysis by extracting aggregate data to synthesise the results as originally planned, mainly because not all studies reported the same outcomes as those chosen for this review. No significant differences favoured VGB or CBZ in terms of time to treatment withdrawal and time to achieve six-month remission after dose stabilisation from randomisation, but results did show a disadvantage for VGB on time to first seizure after randomisation. Compared with CBZ, VGB was associated with more occurrences of weight gain and fewer occurrences of skin rash and drowsiness. No differences in visual field defects and visual disturbances were noted. Data are currently insufficient to address the risk-benefit balance of VGB versus CBZ monotherapy for epilepsy. Given the high prevalence of visual field defects reported in an existing systematic review of observational studies (Maguire 2010), VGB monotherapy should be prescribed with caution for epilepsy and should not be considered a first-line choice. If necessary, the visual field should be frequently assessed. Future research should focus on investigating the reasons for visual field defects and exploring potential prevention strategies. Moreover, future monotherapy studies of epilepsy should report results according to the recommendations of the International League Against Epilepsy (ILAE) Commission, and methodological quality should be improved.",
        "gold": "The evidence is current to July 2015. We found five trials assessing vigabatrin or carbamazepine monotherapy for newly diagnosed epilepsy, which recruited a total of 734 participants between six months and 65 years of age. Results of this review show no significant differences between vigabatrin and carbamazepine in terms of time to treatment withdrawal and time to achieve six-month remission after dose stabilisation from randomisation, but they reveal some clinical disadvantage with vigabatrin on time to first seizure. Taking vigabatrin was more likely to result in weight gain. A safety concern was the high prevalence of visual field defects, as reported in a systematic review of observational studies (Maguire 2010). One study was assessed as good quality and the other four as poor quality."
    },
    {
        "index": "cochrane-simplification-test-194",
        "sentence": "We identified four RCTs fitting the inclusion criteria. However, two of these closed prematurely due to low recruitment and did not report results. The remaining two trials evaluated 600 participants with multiple myeloma or non-Hodgkin lymphoma. In both studies the experimental group received G-CSF plus plerixafor and the control group received G-CSF plus placebo. The meta-analysis showed no evidence for differences between plerixafor and placebo group regarding mortality at 12 months (600 participants; risk ratio (RR) 1.00, 95% confidence interval (CI) 0.59 to 1.69; P = 1.00; moderate-quality evidence) and adverse events during stem cell mobilisation and collection (593 participants; RR 1.02, 95% CI 0.99 to 1.06; P = 0.19; high-quality evidence). Regarding the outcome successful stem cell collection, the meta-analysis showed an advantage for those participants randomised to the plerixafor group (600 participants; RR 2.42, 95% CI 1.98 to 2.96; P < 0.00001; high-quality evidence). As there was high heterogeneity between studies for the number of transplanted participants, we did not meta-analyse these data. In the multiple myeloma study, 95.9% (142 participants) in the plerixafor arm and 88.3% (136 participants) in the placebo arm underwent transplantation (RR 1.09, 95% CI 1.02 to 1.16); in the non-Hodgkin lymphoma trial, 90% (135 participants) in the plerixafor group versus 55.4% (82 participants) in the placebo group could be transplanted (RR 1.62, 95% CI 1.39 to 1.89). In both trials there was no evidence for a difference between participants in the plerixafor and placebo group in terms of time to neutrophil and platelet engraftment in transplanted participants. None of the trials reported on the outcomes quality of life and progression-free survival. The results of the analysed data suggest that additional plerixafor leads to increased stem cell collection in a shorter time. There was insufficient evidence to determine whether additional plerixafor affects survival or adverse events. The two trials included in the meta-analysis, both of which were conducted by the Genzyme Corporation, the manufacturer of plerixafor, were published several times. Two more RCTs examining the addition of plerixafor to a G-CSF mobilisation regimen terminated early without publishing any outcome. The trials included nine and five participants, respectively. Another RCT with 100 participants was recently completed, but has not yet published outcomes. Due to the unpublished RCTs, it is possible that our review is affected by publication bias, even though two trials failed to recruit a sufficient number of participants to analyse any data.",
        "gold": "We searched several medical databases and identified four randomised controlled trials that met our inclusion criteria. Two of the four studies terminated early due to low recruitment (14 participants included) and did not release any results. We were therefore unable to include them in our statistical analysis. The two published analysed trials included 600 participants with multiple myeloma and non-Hodgkin lymphoma. In both studies, the experimental group received G-CSF plus plerixafor subcutaneously, and the control group received G-CSF plus placebo. Both trials were sponsored by Genzyme, the manufacturer of plerixafor. We were able to conduct a meta-analysis of the data of the two studies for the outcomes mortality at 12 months, successful stem cell collection, and adverse events. We found no evidence for a difference between the plerixafor and placebo group for the outcomes mortality at 12 months and adverse events during stem cell mobilisation period. The meta-analysis showed an advantage for those participants randomised to plerixafor for the outcome successful stem cell collection. Furthermore, in both studies the time to collect a defined number of stem cells was significantly shorter in the plerixafor group compared to the placebo group. In the study that enrolled people with multiple myeloma, 95.9% of the participants in the plerixafor arm and 88.3% in the placebo arm underwent transplantation. In the study that examined people with non-Hodgkin lymphoma, 90% of the participants in the plerixafor group and only 55.4% in the placebo group could be transplanted. It seems that especially people with non-Hodgkin lymphoma benefit from the addition of plerixafor in terms of successful transplantation, but there was no evidence for a difference for time to neutrophil and platelet engraftment in transplanted participants. None of the trials reported on quality of life or progression-free survival. The quality of the evidence was high for adverse events and successful stem cell collection and moderate for mortality at 12 months. The main limitation was a wide confidence interval."
    },
    {
        "index": "cochrane-simplification-test-195",
        "sentence": "We included 23 trials involving 1806 women, of whom 717 received cones. All of the trials were small, and in many the quality was hard to judge. Outcome measures differed between trials, making the results difficult to combine. Some trials reported high drop-out rates with both cone and comparison treatments. Seven trials were published only as abstracts. Cones were better than no active treatment (rate ratio (RR) for failure to cure incontinence 0.84, 95% confidence interval (CI) 0.76 to 0.94). There was little evidence of difference for a subjective cure between cones and PFMT (RR 1.01, 95% CI 0.91 to 1.13), or between cones and electrostimulation (RR 1.26, 95% CI 0.85 to 1.87), but the confidence intervals were wide. There was not enough evidence to show that cones plus PFMT was different to either cones alone or PFMT alone. Only seven trials used a quality of life measures and no study looked at economic outcomes. Seven of the trials recruited women with symptoms of incontinence, while the others required women with urodynamic stress incontinence, apart from one where the inclusion criteria were uncertain. This review provides some evidence that weighted vaginal cones are better than no active treatment in women with SUI and may be of similar effectiveness to PFMT and electrostimulation. This conclusion must remain tentative until larger, high-quality trials, that use comparable and relevant outcomes, are completed. Cones could be offered as one treatment option, if women find them acceptable.",
        "gold": "Twenty-three small trials, involving 1806 women, were found. The results of these trials consistently showed that the use of vaginal weights is better than having no treatment. When vaginal weights were compared to other treatments, such as pelvic floor muscle training without the weights, and electrical stimulation of the pelvic floor, no clear differences between the treatments were evident. This may have been because the numbers of participants in the trials were small, and larger numbers may be required for any differences in the effectiveness of treatments to become clear. Some women find vaginal weights unpleasant or difficult to use, so this treatment may not be useful for all women. Many women with stress urinary incontinence will not be cured by these treatments, and so it is important for trials to assess quality of life during and after treatment, but few of these trials did. Most of the trials were of fairly short duration, so it is difficult to say what happens to women with stress urinary incontinence in the longer term."
    },
    {
        "index": "cochrane-simplification-test-196",
        "sentence": "Eleven trials with a total of 2246 AF patients (ranging from 14 to 712 by study) were included within the review. Studies included education, decision aids, and self-monitoring plus education interventions. The effect of self-monitoring plus education on TTR was uncertain compared with usual care (MD 6.31, 95% CI -5.63 to 18.25, I2 = 0%, 2 trials, 69 participants, very low-quality evidence).\u00a0We found small but positive effects of education on anxiety (MD -0.62, 95% CI -1.21 to -0.04, I2 = 0%, 2 trials, 587 participants, low-quality evidence) and depression (MD -0.74, 95% CI -1.34 to -0.14, I2 = 0%, 2 trials, 587 participants, low-quality evidence) compared with usual care. The effect of decision aids on decision conflict favoured usual care (MD -0.1, 95% CI -0.17 to -0.02, I2 = 0%, 2 trials, 721 participants, low-quality evidence). This review demonstrates that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition.",
        "gold": "This is an update of the original review first published in 2013. We searched scientific databases in February 2016 and found 11 randomised clinical trials including 2246 adults with atrial fibrillation who were taking oral anticoagulant medication. The trials we found compared education, decision aids, and self-monitoring plus education to usual care, over any length of time. Few studies had comparable groups and data. There was uncertainty about the effect of self-monitoring plus education on the percentage of time the INR was within the therapeutic range because the proportion or time in the therapeutic range was similar between individuals who received self-monitoring plus education and those who did not. There were small and positive effects on anxiety and depression in individuals who received education compared to those who received usual care. There were small and negative effects on decision conflict in individuals who received decision aids compared to those who received usual care. The evidence should be interpreted with caution as the quality of the evidence ranged from very low to low across different outcomes because of the limitations of individual studies. It is likely that further high-quality trials may affect these reported results."
    },
    {
        "index": "cochrane-simplification-test-197",
        "sentence": "Seventy randomised controlled trials (RCTs) (11,487 women) are included. In this update seven new RCTs (778 women) have been added. Two of these new trials compare PGE2 with no treatment, four compare different PGE2 formulations (gels versus tablets, or sustained release pessaries) and one trial compares PGF2a with placebo. The majority of trials were at unclear risk of bias for most domains. Overall, vaginal prostaglandin E2 compared with placebo or no treatment probably reduces the likelihood of vaginal delivery not being achieved within 24 hours. The risk of uterine hyperstimulation with fetal heart rate changes is increased (4.8% versus 1.0%, risk ratio (RR) 3.16, 95% confidence interval (CI) 1.67 to 5.98, 15 trials, 1359 women). The caesarean section rate is probably reduced by about 10% (13.5% versus 14.8%, RR 0.91, 95% CI 0.81 to 1.02, 36 trials, 6599 women). The overall effect on improving maternal and fetal outcomes (across a variety of measures) is uncertain. PGE2 tablets, gels and pessaries (including sustained release preparations) appear to be as effective as each other, small differences are detected between some outcomes, but these maybe due to chance. Prostaglandins PGE2 probably increase the chance of vaginal delivery in 24 hours, they increase uterine hyperstimulation with fetal heart changes but do not effect or may reduce caesarean section rates. They increase the likelihood of cervical change, with no increase in operative delivery rates. PGE2 tablets, gels and pessaries appear to be as effective as each other, any differences between formulations are marginal but may be important.",
        "gold": "This review set out to determine the effectiveness and safety of vaginal prostaglandins for third trimester cervical ripening and induction of labour (the cervix softens, shortens and opens, the uterus starts to contract regularly). Eight different comparisons were made, different vaginal prostaglandins were compared with placebos or no treatment, or other vaginal prostaglandins (PGE2, PGF2a, except misoprostol) and different preparations and dosages were compared. We identified 70 studies involving a total of 11,487 women. Vaginal prostaglandins increase the likelihood of vaginal birth within 24 hours, but they can also stimulate the uterus to contract too much and this may cause the baby's heart to slow, however they did not increase the caesarean section rate and may reduce it. Overall, the trials do not show any effect (improvement or worsening) of many important outcomes. Prostaglandin E2 tablets, gels, or pessaries including sustained release preparations appear to be as good as each other or the differences between them are small and have not yet been detected in the trials. Lower-dose regimens, as defined in the review, appeared to be as good as higher-dose regimens (eight trials, 1615 women). Very limited data were available in the included trials on time in labour and patient satisfaction. Few studies have addressed issues relating to the safety of using vaginal prostaglandins for induction of labour as outpatients."
    },
    {
        "index": "cochrane-simplification-test-198",
        "sentence": "Eleven potential studies were identified of which five, involving 247 infants, were included in this review. When compared to incubator care, cot-nursing resulted in no significant difference in mean body temperature (MD 0.02 degrees C; 95% CI -0.02 to 0.07, four trials), though the one trial that reported on episodes of hyperthermia found this to be statistically more common in the cot-nursing group (RR 1.48; 95% CI 1.04 to 2.09). There were no statistically significant differences in weight gain. In the cot-nursing group, fewer infants were breast fed on discharge (typical RR 0.74; 95% CI 0.48 to 1.14, three trials, 150 infants) and fewer infants died prior to hospital discharge (typical RR 0.59, 95% CI 0.28 to 1.25, four trials, 235 infants) but these results failed to reach statistical significance. The comparison of cot-nursing using a heated water-filled mattress versus incubator care, which included five trials and a total of 231 infants, produced similar results. Cot-nursing with warming of the nursery resulted in statistically significantly smaller weight gain during week one compared to the incubator group in one trial that involved 38 infants (MD -5.90 g/kg/day; 95% CI -11.13 to -0.67) but no significant difference was found for weeks two and three. Cot-nursing using a heated water-filled mattress has similar effects to incubator care with regard to temperature control and weight gain. Important clinical outcomes need to be investigated further using randomised controlled trials. This is especially the case in the situation of developing countries, where differences in these outcomes are likely to be encountered. As limited data is available on cot-nursing using a space-heated room, this method is not recommended as practice.",
        "gold": "This updated review randomly assigned 247 preterm infants (in five trials), to an intervention of cot-nursing using a heated water-filled mattress. The control babies received routine care in an air heated incubator. One trial had three-arms, including cot-nursing in a room heated with a manually controlled space heater. In the included trials infants in the incubator groups were nursed naked apart from wearing a nappy, except in one trial in which the infants also wore a cotton jacket and booties. Three comparisons were undertaken: the overall comparison of cot-nursing versus incubator care, and two subgroup comparisons: cot-nursing with heated water-filled mattress versus incubator care, and cot-nursing using warming of the nursery versus incubator care. The results of the review showed no evidence of effect of cot-nursing versus incubator care on weight gain in the overall analysis, or in the subgroup analysis comparing cot-nursing using a heated water-filled mattress with incubator care. However, cot-nursing with warming of the nursery during week one when compared to incubator care revealed poorer weight gain. The primary outcomes related to temperature control (mean body temperature and episodes of cold stress) indicated on overall analysis no effect of cot-nursing compared to incubator care. Episodes of hyperthermia in the cot-nursing group were reported more frequently in one trial. The secondary outcomes of oxygen consumption, breast feeding at hospital discharge, episodes of nosocomial sepsis, maternal perceptions of infant's condition, maternal stress and anxiety and death prior to hospital discharge revealed there was no effect of cot-nursing compared to incubator care. There was, however, a strong trend towards less death prior to hospital discharge. This was largely related to the results were obtained from the trials undertaken in Turkey and Ethiopia and thus may not be applicable to neonatal nurseries in developed countries. Nevertheless the implications of these findings deserve consideration, particularly in the context of a developing country."
    },
    {
        "index": "cochrane-simplification-test-199",
        "sentence": "We included three studies, involving 146 participants. Two studies were assessed as being at high risk of bias. The main finding of the review was that the two techniques may be equally successful at exposing PDCs (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.93 to 1.06; three studies, 141 participants analysed, low-quality evidence). One surgical failure was due to detachment of the gold chain (closed group). One study reported on complications following surgery and found two in the closed group: a post-operative infection requiring antibiotics and pain during alignment of the canine as the gold chain penetrated through the gum tissue of the palate. We were unable to pool data for dental aesthetics, patient-reported pain and discomfort, periodontal health and treatment time; however, individual studies did not find any differences between the surgical techniques (low- to very low-quality evidence). Currently, the evidence suggests that neither the open or closed surgical technique for exposing palatally displaced maxillary canine teeth is superior for any of the outcomes included in this review; however, we considered the evidence to be low quality, with two of the three included studies being at high risk of bias. This suggests the need for more high-quality studies. Three ongoing clinical trials have been identified and it is hoped that these will produce data that can be pooled to increase the degree of certainty in these findings.",
        "gold": "The evidence in this review is up-to-date as of February 2017. Authors with Cochrane Oral Health found three relevant studies, involving 146 participants who had eye teeth displaced in the roof of the mouth, either on one or both sides. The majority of participants were female and the average age in the studies ranged from 14 to 17 years. Two studies were designed in a way that made them likely to be biased. We combined results from three studies and found that one technique did not seem to have an advantage over the other for ensuring the movement of the tooth into the correct position without the need for repeat surgery. Five out of 141 participants analysed were surgical failures, one of which was due to the complication of detachment of the gold chain during surgery. One study reported complications after surgery and found one participant in the closed group had a post-operative infection requiring antibiotics and another participant in the closed group experienced pain during alignment of the canine as the gold chain penetrated through the gum tissue of the palate. We were unable to combine results from studies for any other outcomes, but individual studies did not show evidence of a difference between the two techniques for pain, discomfort, appearance, gum health, length of treatment time or cost (low to very low quality evidence). Overall, we assessed the quality of the evidence as low, which means we cannot be certain of the findings. It does not seem that one surgical technique is better than the other for moving displaced eye teeth into the correct position, or for other outcomes, but this finding is uncertain because the quality of the evidence is low. This suggests the need for more high-quality studies. Three studies are currently in process. When they are completed, we will include them in an update of this review and may be able to reach firmer conclusions."
    },
    {
        "index": "cochrane-simplification-test-200",
        "sentence": "We included three trials, involving 244 women. The studies were considered to be at high risk of bias. The prostaglandins used were PG E2 analogue (sulprostone) in 50 participants and PG E1 analogue (misoprostol) in 194 participants at a dose of 250 mcg and 800 mcg respectively. The prostaglandins compared with placebo, were not superior in reducing the rate of manual removal of placenta (average risk ratio (RR) 0.82; 95% confidence interval (CI) 0.54 to 1.27), severe postpartum haemorrhage (RR 0.80; 95% CI 0.55 to 1.15), need for blood transfusion (RR 0.72; 95% CI 0.43 to 1.22), mean blood loss (mean difference (MD) -205.26 mL; 95% CI -536.31 to 125.79, random-effects) and the mean time from injection to placental removal (MD -7.00 minutes; 95% CI -21.20 to 7.20). Side-effects were no different between groups (vomiting, headache, pain and nausea between injection and discharge from the labour ward), with the exception of shivering, which was more frequent in women receiving prostaglandins (RR 10.00; 95% CI 1.40 to 71.49). We did not obtain any data for the primary outcomes of maternal mortality and the need to add another therapeutic uterotonic. Currently there is limited, very low-quality evidence relating to the effectiveness and the safety using prostaglandins for the management of retained placenta. Use of prostaglandins resulted in less need for manual removal of placenta, severe postpartum haemorrhage and blood transfusion but none of the differences reached statistical significance. Much larger, adequately powered studies are needed to confirm that these clinically important beneficial effects are not just chance findings. Similarly, no differences were detected between prostaglandins and placebo in mean blood loss or the mean time from injection to placental removal (minutes) or side-effects (vomiting, headache, pain and nausea between injection and discharge from the labour ward) except for 'shivering' which was more frequent in women who received prostaglandin. The included studies were of poor quality and there is little confidence in the effect estimates; the true effect is likely to be substantially different. We can not make any recommendations about changes to clinical practice. More high-quality research in this area is needed.",
        "gold": "The review identified three randomised controlled studies (involving 244 women) that compared the use of prostaglandins with placebo. Currently there is limited, very low-quality evidence relating to the effectiveness and the safety using prostaglandins for the management of retained placenta. Use of prostaglandins resulted in less need for manual removal of placenta, severe postpartum haemorrhage and need for blood transfusion but none of the differences reached statistical significance. Much larger, adequately powered studies are needed to confirm that these clinically important beneficial effects are not just chance findings. Similarly, no differences were detected between prostaglandins and placebo in mean blood loss or the mean time from injection to placental removal (minutes). The prostaglandin was administered by intravenous infusion (E2 analogue sulprostone) in one study including 50 women and was orally or sublingually administered (E1 analogue misoprostol) in the other two studies including 194 women. Shivering was more frequent in women receiving the prostaglandin but there were no clear differences in vomiting, headache, maternal pain or nausea compared with placebo. The trials were small and of poor methodological quality. The quality of evidence is very low due to study limitations, inconsistency and imprecise results (few women and outcome events with wide confidence intervals). Two studies were stopped early due to an apparent benefit."
    },
    {
        "index": "cochrane-simplification-test-201",
        "sentence": "We included six studies involving 355 infants - two using face mask CPAP, two CNP, one nasal CPAP and one both CNP (for less ill babies) and endotracheal CPAP (for sicker babies). For this update, we included no new trials. Continuous distending pressure (CDP) is associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.65, 95% confidence interval (CI) 0.52 to 0.81; typical risk difference (RD) -0.20, 95% CI -0.29 to -0.10; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 10; six studies; 355 infants), lower overall mortality (typical RR 0.52, 95% CI 0.32 to 0.87; typical RD -0.15, 95% CI -0.26 to -0.04; NNTB 7, 95% CI 4 to 25; six studies; 355 infants) and lower mortality in infants with birth weight above 1500 g (typical RR 0.24, 95% CI 0.07 to 0.84; typical RD -0.28, 95% CI -0.48 to -0.08; NNTB 4, 95% CI 2.00 to 13.00; two studies; 60 infants). Use of CDP is associated with increased risk of pneumothorax (typical RR 2.64, 95% CI 1.39 to 5.04; typical RD 0.10, 95% CI 0.04 to 0.17; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 17.00 to 25.00; six studies; 355 infants). We found no difference in bronchopulmonary dysplasia (BPD), defined as oxygen dependency at 28 days (three studies, 260 infants), as well as no difference in outcome at nine to 14 years (one study, 37 infants). In preterm infants with respiratory distress, the application of CDP as CPAP or CNP is associated with reduced respiratory failure and mortality and an increased rate of pneumothorax. Four out of six of these trials were done in the 1970s. Therefore, the applicability of these results to current practice is difficult to assess. Further research is required to determine the best mode of administration.",
        "gold": "Six studies of moderate quality were identified for inclusion. The source of distending pressure was a negative pressure chamber in two studies, face mask continuous positive airway pressure (CPAP) in two studies, nasal CPAP in one study and negative pressure for less severe illness and endotracheal CPAP when more severe in another study. The studies were small, and four of the six were conducted before surfactant therapy was available. The review of trials found that outcomes for babies were improved. Fewer required IPPV and fewer died, and with these two outcomes combined, fewer babies died or required IPPV. It was also found that CDP can increase the rate of pneumothorax (air outside the lung within the chest cavity). Some meaningful benefits were found when continuous distending pressure (CDP) was used for respiratory distress syndrome in preterm babies."
    },
    {
        "index": "cochrane-simplification-test-202",
        "sentence": "We included six studies (157 participants) in this review. Meta analysis of two studies indicated that foam dressings do not promote the healing of diabetic foot ulcers compared with basic wound contact dressings (RR 2.03, 95%CI 0.91 to 4.55). Pooled data from two studies comparing foam and alginate dressing found no statistically significant difference in ulcer healing (RR 1.50, 95% CI 0.92 to 2.44). There was no statistically significant difference in the number of diabetic foot ulcers healed when foam dressings were compared with hydrocolloid (matrix) dressings. All included studies were small and/or had limited follow-up times. Currently there is no research evidence to suggest that foam wound dressings are more effective in healing foot ulcers in people with diabetes than other types of dressing however all trials in this field are very small. Decision makers may wish to consider aspects such as dressing cost and the wound management properties offered by each dressing type e.g. exudate management.",
        "gold": "Existing reviews have not found evidence that one dressing type is more effective than other types in healing foot ulcers in people with diabetes. This review (157 participants) confirms that currently there is no research evidence to suggest that foam wound dressings are more effective in healing diabetic foot ulcers than other types of dressing. Current decisions on choice of wound dressing if any, should be based where possible, on dressing costs and selecting the most useful management properties offered by each dressing type, for example, the management of wound discharge."
    },
    {
        "index": "cochrane-simplification-test-203",
        "sentence": "We identified three eligible trials. Two trials compared endoscopic intervention with surgical intervention and included a total of 111 participants: 55 in the endoscopic group and 56 in the surgical group. Compared with the endoscopic group, the surgical group had a higher proportion of participants with pain relief, both at middle/long-term follow-up (two to five years: risk ratio (RR) 1.62, 95% confidence interval (CI) 1.22 to 2.15) and long-term follow-up (\u2265 five years, RR 1.56, 95% CI 1.18 to 2.05). Surgical intervention resulted in improved quality of life and improved preservation of exocrine pancreatic function at middle/long-term follow-up (two to five years), but not at long-term follow-up (\u2265 5 years). No differences were found in terms of major post-interventional complications or mortality, although the number of participants did not allow for this to be reliably evaluated. One trial, including 32 participants, compared surgical intervention with conservative treatment: 17 in the surgical group and 15 in the conservative group. The trial showed that surgical intervention resulted in a higher percentage of participants with pain relief and better preservation of pancreatic function. The trial had methodological limitations, and the number of participants was relatively small. For patients with obstructive chronic pancreatitis and dilated pancreatic duct, this review shows that surgery is superior to endoscopy in terms of pain relief. Morbidity and mortality seem not to differ between the two intervention modalities, but the small trials identified do not provide sufficient power to detect the small differences expected in this outcome. Regarding the comparison of surgical intervention versus conservative treatment, this review has shown that surgical intervention in an early stage of chronic pancreatitis is a promising approach in terms of pain relief and pancreatic function. Other trials need to confirm these results because of the methodological limitations and limited number of participants assessed in the present evidence.",
        "gold": "We performed a search in March 2014 and found three relevant randomised trials. Two comparing endoscopic versus surgical interventions (111 patients with durations of two and three years), while the third compared surgery to conservative treatment (i.e. no intervention) (32 patients with a duration of 16 months). We found that surgery achieved pain relief in a higher proportion of participants than endoscopy. Surgery also had other advantages like improved quality of life for the first two years after intervention, although this difference disappeared with time. Similarly, surgery reduced the risk of developing malabsorption due to failure of the pancreas, but with longer follow-up this advantage became smaller. The studies seemingly showed no difference between endoscopy and surgery in complications after interventions. We also compared surgery with conservative treatment. The results of one trial suggested that surgery early in the condition achieved better pain relief and preservation of pancreatic function. For endoscopy versus surgery, the quality of the evidence for pain relief, quality of life and pancreatic function was moderate (according to GRADE). For both complications and mortality this was low, since the two trials were too small to make reliable conclusions. The quality of evidence regarding surgery versus conservative treatment was low, since the trial was small, which precluded drawing reliable conclusions regarding all outcomes."
    },
    {
        "index": "cochrane-simplification-test-204",
        "sentence": "Only one trial was identified for inclusion in this review. This trial was at a high risk of bias. This trial included 857 patients undergoing minor skin excision surgery in the primary care setting. The wounds were sutured after the excision. Patients were randomised to early post-operative bathing (dressing to be removed after 12 hours and normal bathing resumed) (n = 415) or delayed post-operative bathing (dressing to be retained for at least 48 hours before removal and resumption of normal bathing) (n = 442). The only outcome of interest reported in this trial was surgical site infection (SSI). There was no statistically significant difference in the proportion of patients who developed SSIs between the two groups (857 patients; RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients who developed SSIs were 8.5% in the early bathing group and 8.8% in the delayed bathing group. There is currently no conclusive evidence available from randomised trials regarding the benefits or harms of early versus delayed post-operative showering or bathing for the prevention of wound complications, as the confidence intervals around the point estimate are wide, and, therefore, a clinically significant increase or decrease in SSI by early post-operative bathing cannot be ruled out. We recommend running further randomised controlled trials to compare early versus delayed post-operative showering or bathing.",
        "gold": "We identified only one randomised controlled trial. This trial was at high risk of bias, i.e. there were flaws in the way it was conducted that could have given incorrect results.This trial included 857 people undergoing minor skin operations performed at a General Practitioner (GP) surgery. No steri-strips were used in this trial, as the wounds were stitched. The people running the trial used a method similar to the toss of a coin to decide which group participants went into. One group of 415 people was advised to remove the dressing 12 hours after surgery and then to bathe normally, while the other group of 442 people was advised to keep the dressing on for at least 48 hours and then to bathe normally. The only outcome of interest reported in this trial was wound infection. The authors reported no statistically significant difference in the proportion of people who developed wound infection in the two groups (8.5% in the early bathing group and 8.8% in the delayed bathing group). There is currently no conclusive evidence available from randomised trials about the benefits, or harms, with regard to wound complications of early or delayed post-operative showering or bathing. We recommend further randomised controlled trials to compare early versus delayed post-operative showering or bathing."
    },
    {
        "index": "cochrane-simplification-test-205",
        "sentence": "One non-blinded RCT comparing prednisone with no treatment in 35 eligible participants did not measure the primary outcome for this systematic review. The trial had a high risk of bias. Neuropathy Impairment Scale scores after 12 weeks improved in 12 of 19 participants randomised to prednisone, compared with five of 16 participants randomised to no treatment (risk ratio (RR) for improvement 2.02 (95% confidence interval (CI) 0.90 to 4.52; very low-quality evidence). The trial did not report side effects in detail, but one prednisone-treated participant died. A double-blind RCT comparing daily standard-dose oral prednisolone with monthly high-dose oral dexamethasone in 40 participants reported none of the prespecified outcomes for this review. The trial had a low risk of bias, but the quality of evidence was limited as it came from a single small study. There was little or no difference in number of participants who achieved remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly dexamethasone; moderate-quality evidence), or change in disability or impairment after one year (low-quality evidence). Change of grip strength or Medical Research Council (MRC) scores demonstrated little or no difference between groups (moderate-quality to low-quality evidence). Eight of 16 people in the prednisolone group and seven of 24 people in the dexamethasone group deteriorated. Side effects were similar with each regimen, except that sleeplessness was less common with monthly dexamethasone (low-quality evidence) as was moon facies (moon-shaped appearance of the face) (moderate-quality evidence). Experience from large non-randomised studies suggests that corticosteroids are beneficial, but long-term use causes serious side effects. We are very uncertain about the effects of oral prednisone compared with no treatment, because the quality of evidence from the only RCT that exists is very low. Nevertheless, corticosteroids are commonly used in practice, supported by very low-quality evidence from observational studies. We also know from observational studies that corticosteroids carry the long-term risk of serious side effects. The efficacy of high-dose monthly oral dexamethasone is probably little different from that of daily standard-dose oral prednisolone. Most side effects occurred with similar frequencies in both groups, but with high-dose monthly oral dexamethasone moon facies is probably less common and sleeplessness may be less common than with oral prednisolone. We need further research to identify factors that predict response.",
        "gold": "We found one randomised controlled trial (RCT) addressing each question. We did not find any new trials for this update. A 1982 US study compared daily prednisone tablets for 12 weeks with no treatment. Thirty-five people took part. Fourteen participants received prednisone (10 male and four female, with a median age of 46.5 years) and 14 did not receive prednisone (nine male and five female, with a median age of 50 years). Those taking part and the trialists were aware of which treatment the participants received (i.e. they were not 'blinded'), which carries a risk of bias. The second study compared two six-month corticosteroid treatment regimens: daily standard-dose prednisolone tablets, and high-dose dexamethasone tablets for four days each month. Multiple European centres did the trial, which reported its findings in 2010. Forty-one people took part but one person withdrew after one day because they did not want to continue and the diagnosis was wrong. Of those who continued, 24 (18 men and six women, average age 59.9 years) received monthly dexamethasone and 16 (10 men and six women, average age 60.8 years) received daily prednisolone. There was no commercial support for either study. Funding for both came from an academic centre or charitable funds. Neither included study reported our preferred primary outcome, which was a disability score. After 12 weeks, in the trial of prednisone compared to no treatment, 12 of 19 participants on prednisone improved compared with five of 16 participants not on prednisone, based on measurement of disease severity by neurologists. Thus, improvement was about twice as common with prednisone. The small numbers in the trial and its limitations meant that even with this difference we are very uncertain about the size of any effect of prednisone. The trial authors did not report side effects in detail, but one person who received prednisone died. Corticosteroids are commonly used for CIDP in practice, based on favourable reports from non-randomised studies. Corticosteroids are well known to cause side effects, especially when people take large doses for a long time. In the RCT comparing two corticosteroid regimens, 10 of 24 people on monthly dexamethasone and six of 16 people on daily prednisolone were well and off treatment after a year, which indicates effects that are probably similar. Changes in grip strength and scores of muscle strength were also probably similar between the treatment groups. Monthly dexamethasone and daily prednisolone had similar side effects to one another, except that with high-dose monthly dexamethasone, sleeplessness may be less common and a moon-shaped facial appearance is probably less common. The benefit and harm from prednisone in CIDP is uncertain. The quality of evidence is very low because only one small randomised trial with a high risk of bias is available. Monthly dexamethasone and daily prednisolone may be of similar benefit in CIDP, but monthly dexamethasone may have fewer side effects. The evidence is up to date to 8 November 2016."
    },
    {
        "index": "cochrane-simplification-test-206",
        "sentence": "Six studies including a total of 2100 participants met the inclusion criteria: we pooled four studies including 792 people in the main efficacy analyses, and presented the results of a cluster implementation study (n = 1213) and an oral steroid tapering study (n = 95) separately. Baseline characteristics relating to asthma severity were variable, but studies generally recruited people with asthma taking regular medications and excluded those with COPD or severe asthma. One study compared the two types of check-up for oral steroid tapering in severe refractory asthma and we assessed it as a separate question. The studies could not be blinded and dropout was high in four of the six studies, which may have biased the results. We could not say whether more people who had a remote check-up needed oral corticosteroids for an asthma exacerbation than those who were seen face-to-face because the confidence intervals (CIs) were very wide (OR 1.74, 95% CI 0.41 to 7.44; 278 participants; one study; low quality evidence). In the face-to-face check-up groups, 21 participants out of 1000 had exacerbations that required oral steroids over three months, compared to 36 (95% CI nine to 139) out of 1000 for the remote check-up group. Exacerbations that needed treatment in the Emergency Department (ED), hospital admission or an unscheduled healthcare visit all happened too infrequently to detect whether remote check-ups are a safe alternative to face-to-face consultations. Serious adverse events were not reported separately from the exacerbation outcomes. There was no difference in asthma control measured by the Asthma Control Questionnaire (ACQ) or in quality of life measured on the Asthma Quality of Life Questionnaire (AQLQ) between remote and face-to-face check-ups. We could rule out significant harm of remote check-ups for these outcomes but we were less confident because these outcomes are more prone to bias from lack of blinding. The larger implementation study that compared two general practice populations demonstrated that offering telephone check-ups and proactively phoning participants increased the number of people with asthma who received a review. However, we do not know whether the additional participants who had a telephone check-up subsequently benefited in asthma outcomes. Current randomised evidence does not demonstrate any important differences between face-to-face and remote asthma check-ups in terms of exacerbations, asthma control or quality of life. There is insufficient information to rule out differences in efficacy, or to say whether or not remote asthma check-ups are a safe alternative to being seen face-to-face.",
        "gold": "We found a total of six studies including 2100 participants: four studies including 792 people could be pooled for the main results, and two other studies were looked at separately because their designs were very different (n = 1213 and n = 95). People in the four pooled studies in general took regular medications and we excluded those with severe asthma or other lung diseases. We looked at two other studies with very different designs to the main four separately: one compared a practice where people with asthma were given the option of a telephone check-up or a practice visit where they came to the clinic as usual, and one looked specifically at using technology to monitor people while cutting down their oral steroids dose. We last looked for studies on 24 November 2015. We cannot say whether or not people who had a check-up over the phone or internet were more or less likely to need oral corticosteroids for an asthma attack than those seen face-to-face, and we were uncertain of the result for several reasons. Too few people had asthma attacks that needed treatment in the Emergency Department or hospital, or an unscheduled visit to see their doctor to tell if remote check-ups were as good as face-to-face consultations. There didn't appear to be a difference in asthma control or quality of life, but we were able to rule out the possibility that remote check-ups are not as good as face-to-face consultations on these measures. The evidence was all considered to be of low or moderate quality. The study that tested the possible benefit of giving people the option of a telephone check-up showed that this increased the number of people reviewed, but did not show an overall benefit on asthma outcomes."
    },
    {
        "index": "cochrane-simplification-test-207",
        "sentence": "Three out of 16 identified studies met the inclusion criteria, with a total of 212 participants. All the included studies fulfilled at least seven of 10 methodological criteria. The outcome data of the following measures were homogenous and were pooled in a meta-analysis: functional ability (n = 198; WMD -0.07, 95% CI -0.22 to 0.08), quality of life (CHQ-PhS: n = 115; WMD -3.96, 95% CI -8.91 to 1.00) and aerobic capacity (n = 124; WMD 0.04, 95% CI -0.11 to 0.19). The results suggest that the outcome measures all favoured the exercise therapy but none were statistically significant. None of the studies reported negative effects of the exercise therapy. Overall, based on 'silver-level' evidence (www.cochranemsk.org) there was no clinically important or statistically significant evidence that exercise therapy can improve functional ability, quality of life, aerobic capacity or pain. The low number of available RCTs limits the generalisability. The included and excluded studies were all consistent about the adverse effects of exercise therapy; no short-term detrimental effects of exercise therapy were found in any study. Both included and excluded studies showed that exercise does not exacerbate arthritis. The large heterogeneity in outcome measures, as seen in this review, emphasises the need for a standardised assessment or a core set of functional and physical outcome measurements suited for health research to generate evidence about the possible benefits of exercise therapy for patients with JIA. Although the short-term effects look promising, the long-term effect of exercise therapy remains unclear.",
        "gold": "The number of joints with pain was not measured in these studies. We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. No short-term adverse effects of exercise therapy were found in the studies that make up this review. What is exercise therapy and what is JIA? Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is an important cause of short-term and long-term disability. In JIA the cause of the arthritis is unknown. It generally begins in children younger than age 16 years. It always lasts for at least six weeks. A physician will rule out other conditions that may be causing the symptoms before diagnosing JIA. Several types of exercise therapy are described in this review, for example, physical training programs such as strength training for improving muscle strength and endurance exercise for improving overall fitness (either land based or in a pool). Best estimate of what happens to children with JIA and exercise Ability to function: a child's ability to function changed less than 1 more point on a scale of 0 to 3. Other studies state that a change of 0.13 on the score of the Childhood Health Assessment Questionnaire (CHAQ) is a clinically important improvement from the perspective of children and their parents. This level of change has not been found in this review Quality of life: a child's quality of life changed between 2.5 and 4 more points on a scale of 1 to 50. There may be little or no difference with exercise. It is possible that these differences are the result of chance. Adverse effects: no short-term effects have been reported after exercise therapy for children with JIA."
    },
    {
        "index": "cochrane-simplification-test-208",
        "sentence": "We included 19 trials with 2663 participants (11 with outpatients, seven with inpatients, and one with ICU patients). For outpatients (with mild to moderate exacerbations), evidence of low quality suggests that currently available antibiotics statistically significantly reduced the risk for treatment failure between seven days and one month after treatment initiation (RR 0.72, 95% confidence interval (CI) 0.56 to 0.94; I\u00b2 = 31%; in absolute terms, reduction in treatment failures from 295 to 212 per 1000 treated participants, 95% CI 165 to 277). Studies providing older antibiotics not in use anymore yielded an RR of 0.69 (95% CI 0.53 to 0.90; I\u00b2 = 31%). Evidence of low quality from one trial in outpatients suggested no effects of antibiotics on mortality (Peto OR 1.27, 95% CI 0.49 to 3.30). One trial reported no effects of antibiotics on re-exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health-related quality of life but did not show a statistically significant difference between treatment and control groups. Evidence of moderate quality does not show that currently used antibiotics statistically significantly reduced the risk of treatment failure among inpatients with severe exacerbations (i.e. for inpatients excluding ICU patients) (RR 0.65, 95% CI 0.38 to 1.12; I\u00b2 = 50%), but trial results remain uncertain. In turn, the effect was statistically significant when trials included older antibiotics no longer in clinical use (RR 0.76, 95% CI 0.58 to 1.00; I\u00b2 = 39%). Evidence of moderate quality from two trials including inpatients shows no beneficial effects of antibiotics on mortality (Peto OR 2.48, 95% CI 0.94 to 6.55). Length of hospital stay (in days) was similar in antibiotic and placebo groups. The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19, 95% CI 0.08 to 0.45; moderate-quality evidence; in absolute terms, reduction in treatment failures from 565 to 107 per 1000 treated participants, 95% CI 45 to 254). Results of this trial show a statistically significant effect on mortality (Peto OR 0.21, 95% CI 0.06 to 0.72; moderate-quality evidence) and on length of hospital stay (MD -9.60 days, 95% CI -12.84 to -6.36; low-quality evidence). Evidence of moderate quality gathered from trials conducted in all settings shows no statistically significant effect on overall incidence of adverse events (Peto OR 1.20, 95% CI 0.89 to 1.63; moderate-quality evidence) nor on diarrhoea (Peto OR 1.68, 95% CI 0.92 to 3.07; moderate-quality evidence). Researchers have found that antibiotics have some effect on inpatients and outpatients, but these effects are small, and they are inconsistent for some outcomes (treatment failure) and absent for other outcomes (mortality, length of hospital stay). Analyses show a strong beneficial effect of antibiotics among ICU patients. Few data are available on the effects of antibiotics on health-related quality of life or on other patient-reported symptoms, and data show no statistically significant increase in the risk of adverse events with antibiotics compared to placebo. These inconsistent effects call for research into clinical signs and biomarkers that can help identify patients who would benefit from antibiotics, while sparing antibiotics for patients who are unlikely to experience benefit and for whom downsides of antibiotics (side effects, costs, and multi-resistance) should be avoided.",
        "gold": "Evidence gathered for this review is current to September 2018. We found 19 randomised studies that compared antibiotics versus placebo in a total of 2663 COPD patients with a wide range of flare-up severity. Analyses show that currently used antibiotics reduced treatment failures (no improvement in symptoms, despite treatment, within 7 to 28 days, depending on the study) compared with placebo in outpatients with mild to moderate flare-ups, as well as in patients admitted to an intensive care unit for very severe flare-ups with respiratory failure. However, antibiotics did not reduce treatment failures among hospitalised patients with severe flare-ups, although we are less certain about this result because the effect estimate also suggested findings similar to those seen in outpatients, but the confidence interval crossed 1.0. Use of antibiotics led to reduced mortality only in patients admitted to an intensive care unit, but not in patients with mild to moderate (outpatients) or severe (inpatients) flare-ups, although deaths were rare in these latter groups. Antibiotics did not reduce length of hospital stay for hospitalised patients. Patients treated with antibiotics experienced diarrhoea more often than those given placebo, but the difference was not statistically significant. Reviewers could not compare the severity of underlying COPD across trials because trial authors inconsistently reported lung function and other parameters. The quality of evidence for review outcomes was low to moderate. Although trial results show that antibiotics were effective across outcomes for patients with very severe flare-ups and respiratory failure who needed treatment in an intensive care unit, researchers report inconsistent effects in patients with mild to severe flare-ups. Future high-quality studies should examine clinical signs or blood tests at the time of presentation that are useful for identifying patients who can benefit from antibiotic therapy."
    },
    {
        "index": "cochrane-simplification-test-209",
        "sentence": "We included nine RCTs randomising a total of 1414 participants (age range 24 to 70; mean age 45 to 59, where reported) to whole grain versus lower whole grain or refined grain control groups. We found no studies that reported the effect of whole grain diets on total cardiovascular mortality or cardiovascular events (total myocardial infarction, unstable angina, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, total stroke). All included studies reported the effect of whole grain diets on risk factors for cardiovascular disease including blood lipids and blood pressure. All studies were in primary prevention populations and had an unclear or high risk of bias, and no studies had an intervention duration greater than 16 weeks. Overall, we found no difference between whole grain and control groups for total cholesterol (mean difference 0.07, 95% confidence interval -0.07 to 0.21; 6 studies (7 comparisons); 722 participants; low-quality evidence). Using GRADE, we assessed the overall quality of the available evidence on cholesterol as low. Four studies were funded by independent national and government funding bodies, while the remaining studies reported funding or partial funding by organisations with commercial interests in cereals. There is insufficient evidence from RCTs of an effect of whole grain diets on cardiovascular outcomes or on major CVD risk factors such as blood lipids and blood pressure. Trials were at unclear or high risk of bias with small sample sizes and relatively short-term interventions, and the overall quality of the evidence was low. There is a need for well-designed, adequately powered RCTs with longer durations assessing cardiovascular events as well as cardiovascular risk factors.",
        "gold": "We evaluated nine randomised studies assessing the effects of whole grain diets compared to diets with refined grains or a usual diet on levels of cholesterol in the blood or blood pressure (major risk factors for cardiovascular disease including heart attacks or stroke). The evidence is current to August 2016. The diets were followed for at least 12 weeks, but most studies had some methodological limitations, numbers of participants were small, and the overall quality of the evidence was low. We found no studies reporting on the effect of whole grains on deaths from cardiovascular disease or cardiovascular events. All nine included studies reported the effects of whole grain diets on levels of cholesterol in the blood or blood pressure. We found no effects on blood cholesterol or blood pressure in favour of whole grain diets. Four studies were funded by independent national and government funding bodies, while the remaining studies reported funding or partial funding by organisations with commercial interests in cereals. There is insufficient evidence from randomised controlled trials to date to recommend consumption of whole grain diets to reduce the risk of cardiovascular disease, or lower blood cholesterol, or blood pressure."
    },
    {
        "index": "cochrane-simplification-test-210",
        "sentence": "Thirty-eight studies with a total of 1896 participants were included. Only one study was judged at low risk of bias. Eight studies were judged at high risk of selection bias because of lack of allocation concealment and over half the of the studies were at high risk of selective reporting bias. Three small studies investigated rehabilitation interventions during the immobilisation period after conservative orthopaedic management. There was limited evidence from two studies (106 participants in total) of short-term benefit of using an air-stirrup versus an orthosis or a walking cast. One study (12 participants) found 12 weeks of hypnosis did not reduce activity or improve other outcomes. Thirty studies investigated rehabilitation interventions during the immobilisation period after surgical fixation. In 10 studies, the use of a removable type of immobilisation combined with exercise was compared with cast immobilisation alone. Using a removable type of immobilisation to enable controlled exercise significantly reduced activity limitation in five of the eight studies reporting this outcome, reduced pain (number of participants with pain at the long term follow-up: 10/35 versus 25/34; risk ratio (RR) 0.39, 95% confidence interval (CI) 0.22 to 0.68; 2 studies) and improved ankle dorsiflexion range of motion. However, it also led to a higher rate of mainly minor adverse events (49/201 versus 20/197; RR 2.30, 95% CI 1.49 to 3.56; 7 studies). During the immobilisation period after surgical fixation, commencing weight-bearing made a small improvement in ankle dorsiflexion range of motion (mean difference in the difference in range of motion compared with the non-fractured side at the long term follow-up 6.17%, 95% CI 0.14 to 12.20; 2 studies). Evidence from one small but potentially biased study (60 participants) showed that neurostimulation, an electrotherapy modality, may be beneficial in the short-term. There was little and inconclusive evidence on what type of support or immobilisation was the best. One study found no immobilisation improved ankle dorsiflexion and plantarflexion range of motion compared with cast immobilisation, but another showed using a backslab improved ankle dorsiflexion range of motion compared with using a bandage. Five studies investigated different rehabilitation interventions following the immobilisation period after either conservative or surgical orthopaedic management. There was no evidence of effect for stretching or manual therapy in addition to exercise, or exercise compared with usual care. One small study (14 participants) at a high risk of bias found reduced ankle swelling after non-thermal compared with thermal pulsed shortwave diathermy. There is limited evidence supporting early commencement of weight-bearing and the use of a removable type of immobilisation to allow exercise during the immobilisation period after surgical fixation. Because of the potential increased risk of adverse events, the patient's ability to comply with the use of a removable type of immobilisation to enable controlled exercise is essential. There is little evidence for rehabilitation interventions during the immobilisation period after conservative orthopaedic management and no evidence for stretching, manual therapy or exercise compared to usual care following the immobilisation period. Small, single studies showed that some electrotherapy modalities may be beneficial. More clinical trials that are well-designed and adequately-powered are required to strengthen current evidence.",
        "gold": "Thirty-eight studies with a total of 1,896 participants were included in the review. Many of the trials were potentially biased. Three studies examined rehabilitation interventions that started during the immobilisation period after non-surgical treatment. There is some very limited evidence of short term benefit of one type of brace compared with immobilisation with a cast or orthosis. There was no evidence for hypnosis. Thirty studies investigated rehabilitation interventions that started during the immobilisation period after surgical treatment. Ten of these compared the use of a removable type of immobilisation combined with exercise with cast immobilisation alone. There is some evidence from these that using a removable brace or splint so that gentle ankle exercises can be performed during the immobilisation period may enhance the return to normal activities, reduce pain and improve ankle movement. However, the incidence of adverse events (such as problems with the surgical wound) may also be increased. Starting walking early may also slightly improve ankle movement. One small and biased study showed that neurostimulation, an electrotherapy modality, may be beneficial in the short-term. There was little and inconclusive evidence on what type of support or immobilisation was the best. Five studies investigated different rehabilitation interventions that started after the immobilisation period. There is no evidence of improved function for stretching or manual therapy when either of these are added to an exercise programme, or for an exercise programme when this is compared with usual care. One small and potentially biased study found reduced ankle swelling after non-thermal compared with thermal pulsed shortwave diathermy."
    },
    {
        "index": "cochrane-simplification-test-211",
        "sentence": "Four studies met the inclusion criteria. No single intervention was evaluated by more than one trial. Two studies were conducted in low-income countries. Two studies were randomised controlled trials (RCT), and two were non-randomised trials. An RCT of a home-based nursing programme showed a positive effect of the intervention on knowledge and medication refills (p=.002), but no effect on CD4 count and viral load. A second RCT of caregiver medication diaries showed that the intervention group had fewer participants reporting no missed doses compared to the control group (85% vs. 92%, respectively), although this difference was not statistically significant (p=.08). The intervention had no effect on CD4 percentage or viral load. A non-randomised trial of peer support group therapy for adolescents demonstrated no change in self-reported adherence, yet the percentage of participants with suppressed viral load increased from 30% to 80% (p=.06). The second non-randomised trial found that the percentage of children achieving >80% adherence was no different between children on a lopinavir-ritonavir (LPV/r) regimen compared to children on a non-nucleoside reverse transcriptase regimen (p=.781). However, the proportion of children achieving virological suppression was significantly greater for children on the LPV/r regimen than for children on the NNRTI-containing regimen (p=.002). A home-based nursing intervention has the potential to improve ART adherence, but more evidence is needed. Medication diaries do not appear to have an effect on adherence or disease outcomes. Two interventions, an LPV/r-containing regimen and peer support therapy for adolescents, did not demonstrate improvements in adherence, yet demonstrated greater viral load suppression compared to control groups, suggesting a different mechanism for improved health outcomes. Well-designed evaluations of interventions to improve paediatric adherence to ART are needed.",
        "gold": "We identified four studies that evaluated interventions designed to improve adherence to ART among children and adolescents age 18 years and younger. These studies showed that home-based nursing, peer support for adolescents and LPV/r-containing regimens have the potential to improve ART adherence, but more evidence is needed. Medication diaries do not appear to have an effect on adherence. There is a need for well-designed evaluations of interventions to improve paediatric adherence to ART."
    },
    {
        "index": "cochrane-simplification-test-212",
        "sentence": "Five studies (696 participants) met the inclusion criteria; 24 participants were treated with fenoprofen 12.5 mg, 23 with fenoprofen 25 mg, 79 with fenoprofen 50 mg, 78 with fenoprofen 100 mg, 146 with fenoprofen 200 mg, 55 with fenoprofen 300 mg, 43 with zomepirac 100 mg, 30 with morphine 8 mg, 77 with codeine 60 mg, and 141 with placebo. Participants had pain following third molar extraction, laparoscopy, minor day surgery and episiotomy. The NNT for at least 50% pain relief over 4 to 6 hours with a single dose of fenoprofen 200 mg compared to placebo was 2.3 (1.9 to 3.0). There were insufficient data to analyse other doses or active comparators, time to use of rescue medication, or numbers of participants needing rescue medication. There was no difference in numbers of participants experiencing any adverse events between fenoprofen 200 mg and placebo. No serious adverse events or adverse event withdrawals were reported in these studies. Oral fenoprofen 200 mg is effective at treating moderate to severe acute postoperative pain, based on limited data for at least 50% pain relief over 4 to 6 hours. Efficacy of other doses, other efficacy outcomes, and safety and tolerability could not be assessed.",
        "gold": "Five studies looking at a total of 696 participants were included. Because fewer than 200 participants were treated with any one dose of fenoprofen within each study, results must be treated with caution. A good level of pain relief was experienced by better than one in two (over half; 57%) of those with moderate or severe postoperative pain after a single dose of fenoprofen 200 mg, compared to about 1 in 7 (14%) with placebo. This level of pain relief is comparable to that experienced with ibuprofen 400 mg. The frequency of adverse events did not differ between fenoprofen 200 mg and placebo in these studies."
    },
    {
        "index": "cochrane-simplification-test-213",
        "sentence": "Six trials were included; three of these trials are new to this update. Four trials were small (less than 25 women per arm) and two had moderate to high risk of bias. Four trials compared PFMT as a treatment for prolapse against a control group (n = 857 women); two trials included women having surgery for prolapse and compared PFMT as an adjunct to surgery versus surgery alone (n = 118 women). PFMT versus control There was a significant risk of bias in two out four trials in this comparison. Prolapse symptoms and women's reports of treatment outcomes (primary outcomes) were measured differently in the three trials where this was reported: all three indicated greater improvement in symptoms in the PFMT group compared to the control group. Pooling data on severity of prolapse from two trials indicated that PFMT increases the chance of an improvement in prolapse stage by 17% compared to no PFMT. The two trials which measured pelvic floor muscle function found better function (or improvement in function) in the PFMT group compared to the control group; measurements were not known to be blinded. Two out of three trials which measured urinary outcomes (urodynamics, frequency and bother of symptoms, or symptom score) reported differences between groups in favour of the PFMT group. One trial reported bowel outcomes, showing less frequency and bother with symptoms in the PFMT group compared to the control group. PFMT supplementing surgery versus surgery alone Both trials were small and neither measured prolapse-specific outcomes. Pelvic floor muscle function findings differed between the trials: one found no difference between trial groups in muscle strength, whilst the other found a benefit for the PFMT group in terms of stronger muscles. Similarly findings relating to urinary outcomes were contradictory: one trial found no difference in symptom score change between groups, whilst the other found more improvement in urinary symptoms and a reduction in diurnal frequency in the PFMT group compared to the control group. There is now some evidence available indicating a positive effect of PFMT for prolapse symptoms and severity. The largest most rigorous trial to date suggests that six months of supervised PFMT has benefits in terms of anatomical and symptom improvement (if symptomatic) immediately post-intervention. Further evidence relating to effectiveness and cost-effectiveness of PFMT, of different intensities, for symptomatic prolapse in the medium and long term is needed. A large trial of PFMT supplementing surgery is needed to give clear evidence about the usefulness of combining these treatments. Other comparisons which have not been addressed in trials to date and warrant consideration include those involving lifestyle change interventions, and trials aimed at prolapse prevention.",
        "gold": "Six trials were included. Four trials compared pelvic floor muscle training (PFMT) with no intervention, and two trials compared pelvic floor muscle training plus surgery to surgery alone. PFMT compared to no intervention was found in individual trials to improve prolapse symptoms, but data could not be combined. Data on prolapse severity was combined from two trials and results indicated that PFMT increases the chance of improvement in prolapse stage by 17% compared to no treatment. Pelvic floor muscle function appeared to be improved in women who received PFMT in the two trials which measured this. Bladder symptoms were improved with PFMT in two out of three trials measuring this; bowel symptoms were measured in one trial, and an improvement with PFMT was found. The two trials which looked at the benefit of PFMT in addition to surgery, were small but of good quality. Findings were contradictory: women benefited from PFMT, in terms of urinary symptoms and pelvic floor muscle strength, in one trial but not the other. The evidence from the trials suggests there is some benefit from conservative treatment of prolapse, specifically for PFMT as compared to no intervention. More randomised controlled trials are still needed to look at different regimens of PFMT, the cost in relation to benefit, and the long-term effects. The combination of PFMT and surgery requires to be evaluated in a large randomised trial. There is a dearth of trials addressing lifestyle changes as a treatment for prolapse, and trials aimed at prevention of prolapse. Trials of one type of conservative intervention versus another, and combinations of conservative interventions, are also lacking."
    },
    {
        "index": "cochrane-simplification-test-214",
        "sentence": "Fourteen trials (1,724 analysed participants or ears). CSOM definitions and severity varied; some included otitis externa, mastoid cavity infections and other diagnoses. Methodological quality varied; generally poorly reported, follow-up usually short, handling of bilateral disease inconsistent. Topical quinolone antibiotics were better than no drug treatment at clearing discharge at one week: relative risk (RR) was 0.45 (95% confidence interval (CI) 0.34 to 0.59) (two trials, N = 197). No statistically significant difference was found between quinolone and non-quinolone antibiotics (without steroids) at weeks one or three: pooled RR were 0.89 (95% CI 0.59 to 1.32) (three trials, N = 402), and 0.97 (0.54 to 1.72) (two trials, N = 77), respectively. A positive trend in favour of quinolones seen at two weeks was largely due to one trial and not significant after accounting for heterogeneity: pooled RR 0.65 (0.46 to 0.92) (four trials, N = 276) using the fixed-effect model, and 0.64 (95% CI 0.35 to 1.17) accounting for heterogeneity with the random-effects model. Topical quinolones were significantly better at curing CSOM than antiseptics: RR 0.52 (95% CI 0.41 to 0.67) at one week (three trials, N = 263), and 0.58 (0.47 to 0.72) at two to four weeks (four trials, N = 519). Meanwhile, non-quinolone antibiotics (without steroids) compared to antiseptics were more mixed, changing over time (four trials, N = 254). Evidence regarding safety was generally weak. Topical quinolone antibiotics can clear aural discharge better than no drug treatment or topical antiseptics; non-quinolone antibiotic effects (without steroids) versus no drug or antiseptics are less clear. Studies were also inconclusive regarding any differences between quinolone and non-quinolone antibiotics, although indirect comparisons suggest a benefit of topical quinolones cannot be ruled out. Further trials should clarify non-quinolone antibiotic effects, assess longer-term outcomes (for resolution, healing, hearing, or complications) and include further safety assessments, particularly to clarify the risks of ototoxicity and whether quinolones may result in fewer adverse events than other topical treatments.",
        "gold": "Quinolone antibiotic drops (considered to be the 'gold standard' topical antibiotics) are better than no drug treatment or antiseptics at drying the ear. The effects of non-quinolone antibiotics (without steroids) when compared to antiseptics are less clear. Studies were also inconclusive regarding any differences between quinolone and non-quinolone antibiotics, although indirect evidence suggests a benefit of quinolones cannot be ruled out. Less is known about longer-term outcomes (producing a dry ear in the long term, preventing complications, healing the eardrum, and improving hearing), or about treating complicated CSOM. The evidence in these trials about safety is also weak. More research is needed to assess whether there may be fewer adverse events with topical quinolones than with alternative topical treatments."
    },
    {
        "index": "cochrane-simplification-test-215",
        "sentence": "We included 21 studies with a total of 6253 participants (5515 were included in the analysis). Studies were conducted from 1974 to 2011, with 80% of the studies conducted in the 1970's, 1980's or 1990's. Most studies did not report study methods sufficiently and many had high applicability concerns. In 20 studies, FRS differentiated schizophrenia from all other diagnoses with a sensitivity of 57% (50.4% to 63.3%), and a specificity of 81.4% (74% to 87.1%) In seven studies, FRS differentiated schizophrenia from non-psychotic mental health disorders with a sensitivity of 61.8% (51.7% to 71%) and a specificity of 94.1% (88% to 97.2%). In sixteen studies, FRS differentiated schizophrenia from other types of psychosis with a sensitivity of 58% (50.3% to 65.3%) and a specificity of 74.7% (65.2% to 82.3%). The synthesis of old studies of limited quality in this review indicates that FRS correctly identifies people with schizophrenia 75% to 95% of the time. The use of FRS to diagnose schizophrenia in triage will incorrectly diagnose around five to 19 people in every 100 who have FRS as having schizophrenia and specialists will not agree with this diagnosis. These people will still merit specialist assessment and help due to the severity of disturbance in their behaviour and mental state. Again, with a sensitivity of FRS of 60%, reliance on FRS to diagnose schizophrenia in triage will not correctly diagnose around 40% of people that specialists will consider to have schizophrenia. Some of these people may experience a delay in getting appropriate treatment. Others, whom specialists will consider to have schizophrenia, could be prematurely discharged from care, if triage relies on the presence of FRS to diagnose schizophrenia. Empathetic, considerate use of FRS as a diagnostic aid - with known limitations - should avoid a good proportion of these errors. We hope that newer tests - to be included in future Cochrane reviews - will show better results. However, symptoms of first rank can still be helpful where newer tests are not available - a situation which applies to the initial screening of most people with suspected schizophrenia. FRS remain a simple, quick and useful clinical indicator for an illness of enormous clinical variability.",
        "gold": "This review looks at how accurate First Rank Symptoms (FRS) are at diagnosing schizophrenia. FRS are symptoms that people with psychosis may experience, for example hallucinations, hearing voices and thinking that other people can hear their thoughts. We found 21 studies, with 6253 participants, that looked at how good FRS are at diagnosing schizophrenia when compared to a diagnosis made by a psychiatrist. These studies showed that for people who actually have schizophrenia, FRS would only correctly diagnose just over half of them as schizophrenic. For people who do not have schizophrenia, almost 20% would be incorrectly diagnosed with schizophrenia. Therefore, if a person is experiencing a FRS, schizophrenia is a possible diagnosis, but there is also a chance that it is another mental health disorder. We do not recommend that FRS alone can be used to diagnose schizophrenia. However, FRS could be useful to triage patients who need to be assessed by a psychiatrist."
    },
    {
        "index": "cochrane-simplification-test-216",
        "sentence": "We included 10 RCTs, of which 5 were new to this update; all interventions were adjuncts to conventional therapy and were delivered in primary- and secondary-care settings. There were 2003 participants in the 9 educational interventions and 44 participants in the 1 psychological study. Some included studies had methodological weaknesses; for example, we judged four studies to have high risk of detection bias, attrition bias, or other bias. Our primary outcomes were participant-rated global assessment, reduction in disease severity (reported as objective SCORAD (SCORing Atopic Dermatitis)), and improvement in sleep and quality of life. No study reported participant-rated global assessment or improvement of sleep. The largest and most robust study (n = 992) demonstrated significant reduction in disease severity and improvement in quality of life, in both nurse- and dermatologist-led intervention groups. It provided six standardised, age-appropriate group education sessions. Statistically significant improvements in objective severity using the SCORAD clinical tool were recorded for all intervention groups when compared with controls. Improvements in objective severity (intervention minus no intervention) by age group were as follows: age 3 months to 7 years = 4.2, 95% confidence interval (CI) 1.7 to 6.8; age 8 to 12 years = 6.7, 95% CI 2.1 to 11.2; and age 13 to 18 years = 9.9, 95% CI 4.3 to 15.5. In three of five studies, which could not be combined because of their heterogeneity, the objective SCORAD measure was statistically significantly better in the intervention group compared with the usual care groups. However, in all of the above studies, the confidence interval limits do not exceed the minimum clinically important difference of 8.2 for objective SCORAD. The largest study measured quality of life using the German 'Quality of life in parents of children with atopic dermatitis' questionnaire, a validated tool with five subscales. Parents of children under seven years had significantly better improvements in the intervention group on all five subscales. Parents of children aged 8 to 12 years experienced significantly better improvements in the intervention group on 3 of the 5 subscales. This update has incorporated five new RCTs using educational interventions as an adjunct to conventional treatment for children with atopic eczema. We did not identify any further studies using psychological interventions. The inclusion of new studies has not substantially altered the conclusions from the original review. The educational studies in both the original review and this update lack detail about intervention design and do not use a complex interventions framework. Few use an explicit theoretical base, and the components of each intervention are not sufficiently well described to allow replication. A relative lack of rigorously designed trials provides limited evidence of the effectiveness of educational and psychological interventions in helping to manage the condition of atopic eczema in children. However, there is some evidence from included paediatric studies using different educational intervention delivery models (multiprofessional eczema interventions and nurse-led clinics) that these may lead to improvements in disease severity and quality of life. Educational and psychological interventions require further development using a complex interventions framework. Comparative evaluation is needed to examine their impact on eczema severity, quality of life, psychological distress, and cost-effectiveness. There is also a need for comparison of educational interventions with stand-alone psychosocial self-help.",
        "gold": "The main finding of this review is that there is currently only limited research evidence about the effect of educational and psychological approaches when used alongside medicines for the treatment of childhood eczema. Included studies provided a range of interventions, from a single 15-minute consultation to a comprehensive series of sessions delivered to groups of parents over a period of 12 hours. Details of the interventions used and the educational theory base are generally poorly described. Outcome measures varied between studies. Although it is not possible to draw definitive conclusions from this review, several studies using educational interventions demonstrated improvements in eczema severity and quality of life for both children and families. In particular, two studies showed promise. One large study (n = 992) using a multi-disciplinary group education intervention in a hospital setting showed modest improvements in disease severity and quality of life. The single study using psychological approaches indicated that relaxation methods reduced the severity of eczema when compared to discussion only. There is a need for further research into this subject, and priority should be given to comparing the relative cost effectiveness of health professionals educating parents either in teams or by nurses alone. There is also a need for comparison with stand-alone self-help. The most appropriate timeframe for evaluating the effect of interventions should be considered."
    },
    {
        "index": "cochrane-simplification-test-217",
        "sentence": "Fourteen trials contributed to this review (753 participants). There was some moderate quality evidence that HBOT was more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P value = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5; 246 participants, 3 studies). There was also moderate quality evidence of a significantly improved chance of wound breakdown without HBOT following operative treatment for ORN (RR 4.2; 95% CI 1.1 to 16.8, P value = 0.04, NNTB 4; 264 participants, 2 studies). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P value = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P value = 0.0002, NNTB 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P value = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P value = 0.009, NNTB 4). There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no randomised data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse events. These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected participants and tissues may be justified. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should be undertaken.",
        "gold": "There was some evidence that HBOT improved outcome in LRTI affecting bone and soft tissues of the head and neck, for radiation proctitis (inflammation of the lower part of the large intestine caused by radiotherapy treatment) and to prevent the development of osteoradionecrosis (bone death caused by radiotherapy treatment) following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on tissues in the nervous system. The evidence was generally of moderate quality and limited by small numbers of participants, poor reporting of methods and results, and uncertainty as to the exact degree of improvement with HBOT. The application of HBOT to selected participants and tissues may be justified. Studies of radiation injury suggest that other tissues are also likely to respond (e.g. bladder). Further research is required to establish which people may respond and the best timing of such therapy. A study of costs would also be useful."
    },
    {
        "index": "cochrane-simplification-test-218",
        "sentence": "We located 10 RCTs involving 2961 participating surgeons performing an operation in which the use of blunt needles was compared to the use of sharp needles. Four studies focused on abdominal closure, two on caesarean section, two on vaginal repair and two on hip replacement. On average, a surgeon that used sharp needles sustained one glove perforation in three operations. The use of blunt needles reduced the risk of glove perforations with a relative risk (RR) of 0.46 (95% confidence interval (CI) 0.38 to 0.54) compared to sharp needles. The use of blunt needles will thus prevent one glove perforation in every six operations. In four studies, the use of blunt needles reduced the number of self-reported needle stick injuries with a RR of 0.31 (95% CI 0.14 to 0.68). Because the force needed for the blunt needles is higher, their use was rated as more difficult but still acceptable in five out of six studies. The quality of the evidence was rated as high. There is high quality evidence that the use of blunt needles appreciably reduces the risk of exposure to blood and bodily fluids for surgeons and their assistants over a range of operations. It is unlikely that future research will change this conclusion.",
        "gold": "We reviewed the literature to evaluate the preventive effect of blunt needles compared to sharp needles on needle stick injuries among surgical staff. We searched multiple medical databases (to May 2011). We included studies if they were randomised controlled trials (RCTs) of blunt versus sharp suture needles for preventing needle stick injuries among surgical staff. We located 10 RCTs with 2961 operations in which blunt needles were compared to sharp needles. Six studies focused on abdominal operations, two on vaginal repair and two on hip replacement. On average, a surgeon that used sharp needles sustained one glove perforation per three operations. The use of blunt needles reduced the risk of glove perforations by 54% (95% confidence interval 46% to 62%) compared to sharp needles. The use of blunt needles in six operations will thus prevent one glove perforation. In four studies the use of blunt needles also reduced the number of self-reported needle stick injuries by 69% (95% confidence interval 14% to 68%). Even though surgeons reported that the force needed for the blunt needles was higher, their use of the needles was still rated as acceptable in five out of six studies. We concluded that there is high quality evidence that the use of blunt needles appreciably reduces the risk of contracting infectious diseases for surgeons and their assistants over a range of operations by reducing the number of needle stick injuries. It is unlikely that future research will change this conclusion."
    },
    {
        "index": "cochrane-simplification-test-219",
        "sentence": "The review currently includes seven randomised trials involving 422 participants that compared trifluoperazine with low-potency antipsychotic drugs. The size of the included studies was between 20 and 157 participants with a study length between four and 52 weeks. Overall, sequence generation, allocation procedures and blinding were poorly reported.  Trifluoperazine was not significantly different from low-potency antipsychotic drugs in terms of response to treatment (trifluoperazine 26%, low-potency drug 27%, 3 RCTs, n = 120, RR 0.96 CI 0.59 to 1.56, moderate quality evidence). There was also no significant difference in acceptability of treatment with equivocal number of participants leaving the studies early due to any reason (trifluoperazine 20%, low-potency antipsychotics 16%, 3 RCTs, n = 239, RR 1.25, CI 0.72 to 2.17,low quality evidence). There was no significant difference in numbers with at least one adverse effect (trifluoperazine 60%, low-potency antipsychotics 38%, 1 RCT, n = 60, RR 1.60, CI 0.94 to 2.74, moderate quality evidence). However, at least one movement disorder was significantly more frequent in the trifluoperazine group (trifluoperazine 23%, low-potency antipsychotics 13%, 2 RCTs, n = 123, RR 2.08 CI 0.78 to 5.55, very low quality evidence) as well as incoordination (trifluoperazine 20%, low-potency antipsychotics 5%, 1 RCT, n = 60, RR 7.00, CI 1.60 to 30.66) and rigor (trifluoperazine 45%, low-potency antipsychotics 10%, 1 RCT, n = 60, RR 4.50, CI 1.58 to 12.84). No data were available for other outcomes of interest death, sedation and quality of life. The results did not show a difference in efficacy between trifluoperazine and low-potency antipsychotics. Trifluoperazine produced more movement disorders. The number of randomised studies as well as their quality is low, the quality of evidence for outcomes of interest ranged from moderate to very low quality, so more, newer studies would be needed for conclusions about the relative effects of trifluoperazine and low-potency antipsychotics.",
        "gold": "Antipsychotic drugs are the main treatment for schizophrenia, they help people cope with symptoms such as hearing voices, seeing things and having strange beliefs. Guidelines state that there is no difference in effectiveness between antipsychotics, but low-potency antipsychotic drugs are often seen as less effective than high-potency drugs, and they also seem to differ in side-effects. The classification into high-potency and low-potency medication means that low-potency antipsychotic drugs need higher doses for treating the symptoms of schizophrenia. Side-effects that are common to most high-potency antipsychotic drugs include the movement disorders such as uncontrollable movements of the face, arms, or legs; tremors; problems with balance or walking; restlessness; seizures; joint pain whereas low-potency drugs are more likely to cause sedation, fever and loss of muscle strength. Research has not evaluated and compared high-potency drugs with low-potency antipsychotic drugs. The aim of the review was therefore to compare trifluoperazine (a high-potency antipsychotic) with low-potency antipsychotics for people with schizophrenia. Examples of low-potency drugs are chlorpromazine, chlorprothixene, thioridazine and levomepromazine.\u00a0The review is based on a search carried out in 2010 and included seven studies with a total of 422 people.\u00a0It compared trifluoperazine with low-potency antipsychotic drugs. Overall, information was poorly reported and the quality of the studies was low; authors rated the quality of evidence for the main outcomes of interested as being either moderate, low or very low quality.\u00a0Results do not show a superiority of trifluoperazine compared with low-potency antipsychotics.\u00a0However, at least one movement disorder (muscle stiffness) was significantly more with trifluoperazine. For people with schizophrenia it is important to know that trifluoperazine and low-potency antipsychotics are approximately equal for dealing with symptoms such as hearing voices or seeing things.\u00a0They differ slightly in their side-effects, with trifluoperazine leading to at least one movement disorder (muscle stiffness). However, no clear superiority of trifluoperazine versus low-potency antipsychotics was found.\u00a0Due to the limited number of studies, participants and low quality of information, these results have to be interpreted with caution. This plain language summary has been written by a consumer Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness."
    },
    {
        "index": "cochrane-simplification-test-220",
        "sentence": "We found nine eligible RCTs including 593 infants in total. These trials compared responsive with scheduled interval regimens in preterm infants in the transition phase from intragastric tube to oral feeding. The trials were generally small and contained various methodological weaknesses including lack of blinding and incomplete assessment of all randomised participants. Meta-analyses, although limited by data quality and availability, suggest that responsive feeding results in slightly slower rates of weight gain (MD \u22121.36, 95% CI \u22122.44 to \u22120.29 g/kg/day), and provide some evidence that responsive feeding reduces the time taken for infants to transition from enteral tube to oral feeding (MD \u22125.53, 95% CI \u22126.80 to \u22124.25 days). GRADE assessments indicated low quality of evidence. The importance of this finding is uncertain as the trials did not find a strong or consistent effect on the duration of hospitalisation. None of the included trials reported any parent, caregiver, or staff views. Overall, the data do not provide strong or consistent evidence that responsive feeding affects important outcomes for preterm infants or their families. Some (low quality) evidence exists that preterm infants fed in response to feeding and satiation cues achieve full oral feeding earlier than infants fed prescribed volumes at scheduled intervals. This finding should be interpreted cautiously because of methodological weaknesses in the included trials. A large RCT would be needed to confirm this finding and to determine if responsive feeding of preterm infants affects other important outcomes.",
        "gold": "We searched for all available evidence up to January 2016. We found nine eligible randomised controlled trials (including a total of 593 infants) that examined whether feeding preterm infants in response to their own feeding and satiation cues (sometimes called 'demand' feeding) is better than feeding set volumes of milk at predefined intervals. These trials compared responsive with scheduled interval regimens in preterm infants in the transition phase from intragastric tube to oral feeding. Although the trials were generally small and most had some methodological weaknesses, analysis suggests that responsive feeding results in slightly slower rates of weight gain and reduces the time taken for infants to transition from enteral tube to oral feeding. The quality of this evidence is low, and the importance of this finding is uncertain as the trials did not find a strong or consistent effect on the length of hospitalisation. None of the included trials reported any parent, caregiver, or staff views. This Cochrane review does not provide strong or consistent evidence that responsive feeding improves outcomes for preterm infants or their families. Responsive feeding might help infants transition more quickly to oral feeding, but more randomised controlled trials would be needed to confirm this finding."
    },
    {
        "index": "cochrane-simplification-test-221",
        "sentence": "Two randomised trials with a total of 161 participants were included in this review. The studies did not report on mortality and rate of limb loss. One randomised trial with a total of 133 participants showed that there was a significant improvement in ankle brachial index (ABI) in participants who received folic acid compared with placebo (mean difference (MD) 0.07, 95% confidence interval (CI) 0.04 to 0.11, P < 0.001) and in participants who received 5-methyltetrahydrofolate (5-MTHF) versus placebo (MD 0.05, 95% CI 0.01 to 0.10, P = 0.009). A second trial with a total of 18 participants showed that there was no difference (P non-significant) in ABI in participants who received a multivitamin B supplement (mean \u00b1 SEM: 0.7 \u00b1 01) compared with placebo (mean \u00b1 SEM: 0.8 \u00b1 0.1). No major events were reported. Currently, no recommendation can be made regarding the value of treatment of hyperhomocysteinaemia in peripheral arterial disease. Further, well constructed trials are urgently required.",
        "gold": "We looked at studies where treatments to lower homocysteine were used in people with PAD and hyperhomocysteinaemia. Two trials with 161 participants with PAD were included in this review. One trial showed a significant\u00a0 improvement in the ankle brachial index (ABI) in participants treated daily with 400 \u03bcg folic acid or 5-methyltetrahydrofolate (5-MTHF). A second trial showed that there was no difference in ABI in participants who received a multivitamin B supplement compared with placebo. None of the other predefined primary outcomes (mortality and rate of limb loss) were assessed in these studies. More research about the effect of homocysteine lowering therapy on the clinical progression of disease in people with PAD and hyperhomocysteinaemia is needed."
    },
    {
        "index": "cochrane-simplification-test-222",
        "sentence": "Two cluster-RCTs, with data from 503 dental practices, representing 821 dentists and 4771 patients, met the selection criteria. We judged the risk of bias to be high for both studies and the overall quality of the evidence was low/very low for all outcomes, as assessed using the GRADE approach. One study used a factorial design to investigate the impact of fee-for-service and an educational intervention on the placement of fissure sealants in permanent molar teeth. The authors reported a statistically significant increase in clinical activity in the arm that was incentivised with a fee-for-service payment. However, the study was conducted in the four most deprived areas of Scotland, so the applicability of the findings to other settings may be limited. The study did not report data on measures of health service utilisation or measures of patient outcomes. The second study used a parallel group design undertaken over a three-year period to compare the impact of capitation payments with fee-for-service payments on primary care dentists\u2019 clinical activity. The study reported on measures of clinical activity (mean percentage of children receiving active preventive advice, health service utilisation (mean number of visits), patient outcomes (mean number of filled teeth, mean percentage of children having one or more teeth extracted and the mean number of decayed teeth) and healthcare costs (mean expenditure). Teeth were restored at a later stage in the disease process in the capitation system and the clinicians tended to see their patients less frequently and tended to carry out fewer fillings and extractions, but also tended to give more preventive advice. There was insufficient information regarding the cost-effectiveness of the different remuneration methods. Financial incentives within remuneration systems may produce changes to clinical activity undertaken by primary care dentists. However, the number of included studies is limited and the quality of the evidence from the two included studies was low/very low for all outcomes. Further experimental research in this area is highly recommended given the potential impact of financial incentives on clinical activity, and particular attention should be paid to the impact this has on patient outcomes.",
        "gold": "Our review identified two studies examining the effects of different methods of remuneration on the behaviour of 821 dentists from 503 dental practices, involving 4771 patients. Both were conducted in the United Kingdom. One study investigated the impact of a fee-for-service payment and an educational intervention on the placement of fissure sealants in permanent molar teeth. The second study compared the impact of capitation payments and fee-for-service payments on primary care dentists\u2019 clinical activity and the levels of dental decay that were experienced across the two payment systems. The first study found an increase in clinical activity related to fee-for-service payments. In the second study, dentists working under capitation arrangements restored carious teeth at a later stage in the disease process than fee-for-service controls. In the capitation arm, the dentists tended to see their patients less frequently and tended to carry out fewer fillings and extractions, but tended to give more preventive advice. There was insufficient information regarding cost-effectiveness of the different remuneration methods. Financial incentives within remuneration systems may produce changes to clinical activity undertaken by primary care dentists. However, the number of included studies is limited and the quality of the evidence is low/very low for all outcomes."
    },
    {
        "index": "cochrane-simplification-test-223",
        "sentence": "We included 21 randomised controlled trials (RCTs) reported in 54 papers involving over 17,000 women and their babies. One trial did not contribute data. Trials were generally at low risk of bias. Zinc supplementation resulted in a small reduction in preterm birth (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.76 to 0.97 in 16 RCTs; 16 trials of 7637 women). This was not accompanied by a similar reduction in numbers of babies with low birthweight (RR 0.93, 95% CI 0.78 to 1.12; 14 trials of 5643 women). No clear differences were seen between the zinc and no zinc groups for any of the other primary maternal or neonatal outcomes, except for induction of labour in a single trial. No differing patterns were evident in the subgroups of women with low versus normal zinc and nutrition levels or in women who complied with their treatment versus those who did not. The GRADE quality of the evidence was moderate for preterm birth, small-for-gestational age, and low birthweight, and low for stillbirth or neonatal death and birthweight. The evidence for a 14% relative reduction in preterm birth for zinc compared with placebo was primarily represented by trials involving women of low income and this has some relevance in areas of high perinatal mortality. There was no convincing evidence that zinc supplementation during pregnancy results in other useful and important benefits. Since the preterm association could well reflect poor nutrition, studies to address ways of improving the overall nutritional status of populations in impoverished areas, rather than focusing on micronutrient and or zinc supplementation in isolation, should be an urgent priority.",
        "gold": "Many women of childbearing age may have mild to moderate zinc deficiency. Low zinc concentrations may cause preterm birth or they may even prolong labour. It is also possible that zinc deficiency may affect infant growth as well. This review of 21 randomised controlled trials, involving over 17,000 women and their babies, found that although zinc supplementation has a small effect on reducing preterm births, it does not help to prevent low birthweight babies compared with not giving zinc supplements before 27 weeks of pregnancy. One trial did not contribute data. The overall risk of bias was unclear in half of the studies. No clear differences were seen for development of pregnancy hypertension or pre-eclampsia. The 14% relative reduction in preterm birth for zinc compared with placebo was primarily represented by trials of women with low incomes. In some trials all women were also given iron, folate or vitamins or combinations of these. UNICEF is already promoting antenatal use of multiple-micronutrient supplementation, including zinc, to all pregnant women in developing countries. Finding ways to improve women's overall nutritional status, particularly in low-income areas, will do more to improve the health of mothers and babies than supplementing pregnant women with zinc alone. In low- to middle- income countries, addressing anaemia and infections, such as malaria and hookworm, is also necessary."
    },
    {
        "index": "cochrane-simplification-test-224",
        "sentence": "Ten RCTs (1656 participants) met our inclusion criteria, and pharmaceutical industry funded none of these trials. All trials used probiotics as adjuvant therapy to antifungal drugs. Probiotics increased the rate of short-term clinical cure (risk ratio (RR) 1.14, 95% confidence interval (CI) 1.05 to 1.24, 695 participants, 5 studies, low quality evidence) and mycological cure (RR 1.06, 95% CI 1.02 to 1.10, 969 participants, 7 studies, low quality evidence) and decreased relapse rate at one month (RR 0.34, 95% CI 0.17 to 0.68, 388 participants, 3 studies, very low quality evidence). However, this effect did not translate into a higher frequency of long-term clinical cure (one month after treatment: RR 1.07, 95% CI 0.86 to 1.33, 172 participants, 1 study, very low quality evidence; three months after treatment: RR 1.30, 95% CI 1.00 to 1.70, 172 participants, one study, very low quality evidence) or mycological cure (one month after treatment: RR 1.26, 95% CI 0.93 to 1.71, 627 participants, 3 studies, very low quality evidence; three months after treatment: RR 1.16, 95% CI 1.00 to 1.35, 172 participants, one study, very low quality evidence). Probiotics use did not increase the frequency of serious (RR 0.80, 95% CI 0.22 to 2.94; 440 participants, 2 studies, low quality evidence). We found no eligible RCTs for outcomes as time to first relapse, need for additional treatment at the end of therapy, patient satisfaction and cost effectiveness. Low and very low quality evidence shows that, compared with conventional treatment, the use of probiotics as an adjuvant therapy could increases the rate of short-term clinical and mycological cure and decrease the relapse rate at one month but this did not translate into a higher frequency of long-term clinical or mycological cure. Probiotics use does not seem to increase the frequency of serious or non-serious adverse events. There is a need for well-designed RCTs with standardized methodologies, longer follow-up and larger sample size.",
        "gold": "We searched evidence up to October 2017 and included 10 clinical trials with 1656 participants. The trials lasted between three months and five years. All trials used at least one laboratory method for diagnosis. Four trials compared vaginal suppository (solid medicine inserted directly into the vagina) or tablet of clotrimazole (antifungal medicine) plus vaginal capsules of probiotics with vaginal suppository or tablet of clotrimazole alone. Three trials compared vaginal suppository of miconazole (antifungal medicine) plus vaginal capsules of probiotics with vaginal suppository of miconazole alone. Two trials compared oral fluconazole (antifungal medicine) plus oral capsules of probiotics with oral fluconazole plus oral capsules of placebo (pretend treatment). One trial compared oral fluconazole and vaginal fenticonazole (antifungal medicines) with oral fluconazole plus vaginal fenticonazole plus probiotic. Compared with conventional antifungal drugs used alone, probiotics as adjuvant therapy could enhance their effect in improving the rate of short-term (within five to 10 days) clinical cure, short-term mycological cure (no abnormal laboratory results) and relapse at one month (recurrence of problems), but does not seem to influence the rate of long-term (within one to three months) clinical cure, long-term mycological cure, serious and non-serious side events. However, because of the low quality of evidence available, there is insufficient evidence for the use of probiotics as adjuvants to conventional antifungal medicines or used alone for the treatment of VVC in non-pregnant women. The quality of the evidence was low or very low in this review, so we have very little confidence in the results."
    },
    {
        "index": "cochrane-simplification-test-225",
        "sentence": "We included seven trials (involving 696 participants) in this update of the review. The included trials were conducted in different countries, covering the full spectrum of the World Bank's economic classification, which enhances the applicability of evidence drawn from this review. Two trials were conducted in Germany and Italy which are high-income countries, while four trials were conducted in upper-middle income countries; two in Iran, one in Malaysia and the fourth in Turkey, and the seventh trial was conducted in Jordan, which is a lower-middle income country. In six trials all the participants met the inclusion criteria and in the seventh study, we included in the meta-analysis only the subgroup of participants who met the inclusion criteria. We assessed the body of evidence for the main outcomes using the GRADE tool and the quality of the evidence ranged from very low to moderate. Downgrading of evidence was based on the high risk of bias in six of the seven included trials and a small number of events and wide confidence intervals for some outcomes. Treatment of miscarriage with progestogens compared to placebo or no treatment probably reduces the risk of miscarriage; (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.47 to 0.87; 7 trials; 696 women; moderate-quality evidence). Treatment with oral progestogen compared to no treatment also probably reduces the miscarriage rate (RR 0.57, 95% CI 0.38 to 0.85; 3 trials; 408 women; moderate-quality evidence). However treatment with vaginal progesterone compared to placebo, probably has little or no effect in reducing the miscarriage rate (RR 0.75, 95% CI 0.47 to 1.21; 4 trials; 288 women; moderate-quality evidence). The subgroup interaction test indicated no difference according to route of administration between the oral and vaginal subgroups of progesterone. Treatment of miscarriage with the use of progestogens compared to placebo or no treatment may have little or no effect in reducing the rate of preterm birth (RR 0.86, 95% CI 0.52 to 1.44; 5 trials; 588 women; low-quality evidence). We are uncertain if treatment of threatened miscarriage with progestogens compared to placebo or no treatment has any effect on the rate of congenital abnormalities because the quality of the evidence is very low (RR 0.70, 95% CI 0.10 to 4.82; 2 trials; 337 infants; very-low quality evidence). The results of this Cochrane Review suggest that progestogens are probably effective in the treatment of threatened miscarriage but may have little or no effect in the rate of preterm birth. The evidence on congenital abnormalities is uncertain, because the quality of the evidence for this outcome was based on only two small trials with very few events and was found to be of very low quality.",
        "gold": "In this review of the literature, up to August 2017, we identified seven randomised trials involving 696 women that compared the use of progestogens in the treatment of threatened miscarriage with either placebo or no treatment. We found that the use of a progestogen probably reduces the rate of spontaneous miscarriage and this was supported by moderate-quality evidence. Five trials, involving 588 women, reported on the effectiveness of progestogens given for threatened miscarriage in reducing the rate of preterm delivery and showed little or no effect, with low-quality evidence. Two trials, involving 337 women, reported on the effect of treatment with progestogens given for threatened miscarriage on the rate of occurrence of congenital abnormalities in the newborns. The evidence on congenital abnormalities is uncertain, because the quality of the evidence for this outcome was based on only two small trials with very few events and was found to be of very low quality. The evidence suggests that progesterone probably reduces the rate of spontaneous miscarriage but may make little or no difference to the number of preterm deliveries. The evidence for congenital abnormalities is uncertain because the quality of the evidence for this outcome was based on only two small trials with very few events and was found to be of very low quality."
    },
    {
        "index": "cochrane-simplification-test-226",
        "sentence": "We identified a large number of trials of laser photocoagulation of diabetic retinopathy (n = 83) but only five of these studies were eligible for inclusion in the review, i.e. they compared laser photocoagulation with currently available lasers to no (or deferred) treatment. Three studies were conducted in the USA, one study in the UK and one study in Japan. A total of 4786 people (9503 eyes) were included in these studies. The majority of participants in four of these trials were people with proliferative diabetic retinopathy; one trial recruited mainly people with non-proliferative retinopathy. Four of the studies evaluated panretinal photocoagulation with argon laser and one study investigated selective photocoagulation of non-perfusion areas. Three studies compared laser treatment to no treatment and two studies compared laser treatment to deferred laser treatment. All studies were at risk of performance bias because the treatment and control were different and no study attempted to produce a sham treatment. Three studies were considered to be at risk of attrition bias. At 12 months there was little difference between eyes that received laser photocoagulation and those allocated to no treatment (or deferred treatment), in terms of loss of 15 or more letters of visual acuity (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.89 to 1.11; 8926 eyes; 2 RCTs, low quality evidence). Longer term follow-up did not show a consistent pattern, but one study found a 20% reduction in risk of loss of 15 or more letters of visual acuity at five years with laser treatment. Treatment with laser reduced the risk of severe visual loss by over 50% at 12 months (RR 0.46, 95% CI 0.24 to 0.86; 9276 eyes; 4 RCTs, moderate quality evidence). There was a beneficial effect on progression of diabetic retinopathy with treated eyes experiencing a 50% reduction in risk of progression of diabetic retinopathy (RR 0.49, 95% CI 0.37 to 0.64; 8331 eyes; 4 RCTs, low quality evidence) and a similar reduction in risk of vitreous haemorrhage (RR 0.56, 95% CI 0.37 to 0.85; 224 eyes; 2 RCTs, low quality evidence). None of the studies reported near visual acuity or patient-relevant outcomes such as quality of life, pain, loss of driving licence or adverse effects such as retinal detachment. We did not plan any subgroup analyses, but there was a difference in baseline risk in participants with non-proliferative retinopathy compared to those with proliferative retinopathy. With the small number of included studies we could not do a formal subgroup analysis comparing effect in proliferative and non-proliferative retinopathy. This review provides evidence that laser photocoagulation is beneficial in treating proliferative diabetic retinopathy. We judged the evidence to be moderate or low, depending on the outcome. This is partly related to reporting of trials conducted many years ago, after which panretinal photocoagulation has become the mainstay of treatment of proliferative diabetic retinopathy. Future Cochrane Reviews on variations in the laser treatment protocol are planned. Future research on laser photocoagulation should investigate the combination of laser photocoagulation with newer treatments such as anti-vascular endothelial growth factors (anti-VEGFs).",
        "gold": "We found five studies. The searches were done in April 2014. Three studies were done in the USA, one study in the UK and one study in Japan. A total of 4786 people (9503 eyes) were included in these studies. Most participants had PDR. We found that moderate vision loss at 12 months was similar in eyes treated with laser and eyes that were not treated, but similar assessments made at a later date showed that eyes treated with laser were less likely to have suffered moderate vision loss. Treatment with laser reduced the risk of severe visual loss by over 50% at 12 months. There was a similar effect on the progression of DR. None of the studies reported patient-relevant outcomes such as pain or loss of driving licence. We did not find very many studies and those we found were done quite a long time ago when standards of trial conduct and reporting were lower. We judged the quality of the evidence to be low, with the exception of the results for severe visual loss, which we judged to be moderate quality evidence."
    },
    {
        "index": "cochrane-simplification-test-227",
        "sentence": "We included two trials involving 269 participants. The participants were mostly men (67%); the mean age was 65 years. The trials were conducted in China and Italy (one was a multicentre trial). Both trials included adults with acute respiratory failure after upper abdominal surgery. We judged both trials at high risk of bias. Compared to oxygen therapy, CPAP or bilevel NPPV may reduce the rate of tracheal intubation (risk ratio (RR) 0.25; 95% confidence interval (CI) 0.08 to 0.83; low quality evidence) with a number needed to treat for an additional beneficial outcome of 11. There was very low quality evidence that the intervention may also reduce ICU length of stay (mean difference (MD) -1.84 days; 95% CI -3.53 to -0.15). We found no differences for mortality (low quality evidence) and hospital length of stay. There was insufficient evidence to be certain that CPAP or NPPV had an effect on anastomotic leakage, pneumonia-related complications, and sepsis or infections. Findings from one trial of 60 participants suggested that bilevel NPPV, compared to oxygen therapy, may improve blood gas levels and blood pH one hour after the intervention (partial pressure of arterial oxygen (PaO2): MD 22.5 mm Hg; 95% CI 17.19 to 27.81; pH: MD 0.06; 95% CI 0.01 to 0.11; partial pressure of arterial carbon dioxide (PCO2) levels (MD -9.8 mm Hg; 95% CI -14.07 to -5.53). The trials included in this systematic review did not present data on the following outcomes that we intended to assess: gastric insufflation, fistulae, pneumothorax, bleeding, skin breakdown, eye irritation, sinus congestion, oronasal drying, and patient-ventilator asynchrony. The findings of this review indicate that CPAP or bilevel NPPV is an effective and safe intervention for the treatment of adults with acute respiratory failure after upper abdominal surgery. However, based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, the quality of the evidence was low or very low. More good quality studies are needed to confirm these findings.",
        "gold": "We searched scientific databases for clinical trials looking at the treatment of adults with acute respiratory failure following abdominal surgery. The trials compared NPPV with usual care(oxygen therapy through a face mask). We included two trials involving 269 participants.The participants were mostly men (67%) and on average 65 years of age. One trial was conducted in several intensive care units (ICU). Both trials included adults with acute respiratory failure after upper abdominal surgery. The evidence is current to May 2015. This review examined mortality, rate of tracheal intubation, length of stay in the ICU, length of hospital stay, complications after NPPV, and changes in the levels of gases within the blood (arterial blood gases). Compared with oxygen therapy, NPPV decreased the rate of tracheal intubation. Out of every 1000 adults who developed acute respiratory failure after upper abdominal surgery, 181 adults treated with oxygen therapy would need to be intubated compared with 54 adults treated with NPPV. When compared to oxygen therapy, NPPV tended to reduce mortality. However, since the number of participants included in the two trials was small, more studies are needed. The use of NPPV also reduced the length of stay in the ICU by almost two days when compared to oxygen therapy. However, the mean length of stay in the hospital was similar in the two groups. When compared to oxygen therapy, NPPV improved blood gas levels one hour after the intervention. There was insufficient evidence to be certain that CPAP or NPPV had an effect on anastomotic (e.g. where two pieces of intestine are joined together) leakage, pneumonia related complications and sepsis (blood poisoning) or infections. However, adults treated with NPPV had lower rates these complications than adults treated with oxygen. There was low quality evidence for hospital mortality, low quality of evidence for rate of tracheal intubation, and very low quality of evidence for ICU length of stay. The findings of this review showed that NPPV is an effective and safe treatment for adults with acute respiratory failure after upper abdominal surgery. However, due to the low quality of the evidence, more good quality studies are needed to confirm these findings."
    },
    {
        "index": "cochrane-simplification-test-228",
        "sentence": "We included four trials involving 388 women that were judged to be at an unclear to high risk of bias overall. A variety of different agents for providing analgesia were assessed in the trials, and a number of different methods to measure pain relief were used, and thus results could not be combined in meta-analysis. Three trials compared diazepam with an alternative agent (ketamine; vinydan-ether; \"other\" anaesthesic agent) for the provision of general anaesthesia, and one trial compared spinal analgesia to pudendal nerve block (in both groups lignocaine was administered). With regard to the primary outcomes, women receiving diazepam for forceps delivery in one small trial were more likely to judge their pain relief as effective compared with women receiving vinydan-ether (risk ratio (RR) 1.13; 95% confidence interval (CI) 1.02 to 1.25; 101 women). In a further small trial, no significant difference was seen in the number of women judging their pain relief as effective when diazepam was compared with ketamine (RR 1.42; 95% CI 0.98 to 2.07; 26 women). In the trial that compared spinal analgesia to pudendal nerve block, women receiving spinal analgesia were significantly more likely to regard their analgesia as adequate (RR 3.36; 95% CI 2.46 to 4.60; 183 women) and were less likely to report severe pain during forceps delivery (RR 0.02; 95% CI 0.00 to 0.27; 183 women). No trials reported on the review's other two primary outcomes of serious maternal adverse effects or complications, and neonatal mortality or serious morbidity. In terms of secondary outcomes, women receiving diazepam compared with vinydan-ether, were significantly less likely to experience vomiting (RR 0.04; 95% CI 0.00 to 0.62; 101 women). No significant differences were seen for the few neonatal outcomes that were reported across any of the comparisons (including Agpar score of less than seven at five minutes and acidosis as defined by cord blood arterial pH less than 7.2). There is insufficient evidence to support any particular analgesic agent or method as most effective in providing pain relief for forceps delivery. Neonatal outcomes have largely not been evaluated.",
        "gold": "This review found that there is not enough evidence from the four included randomised controlled trials, involving 388 women and their babies, to determine the most effective and safe analgesic agent or technique for women who are undergoing a forceps delivery. Three of the four trials compared diazepam with alternative agents (ketamine, vinydan-ether, or \"other\" anaesthesic agent) to provide general anaesthesia during forceps delivery. A number of different methods were used to measure pain relief and the results could not be combined. The data from one trial could not be included in the review. Women who received diazepam were more likely to judge their pain relief as effective compared with women who received vinydan-ether in one small trial. In another small trial, however, no difference in pain relief was shown when diazepam was compared with ketamine. In the trial that compared spinal analgesia with pudendal nerve block, women receiving spinal analgesia were more likely to report their pain relief as adequate and were less likely to report severe pain. None of the four trials reported on serious complications or death for the mother or baby. The included trials had a high or unclear risk of bias and were not of a high quality. Each of the four included trials was conducted prior to 1980 and assessed agents or methods that are not commonly used in clinical practice today. Therefore, more studies are needed to establish what drug, or technique, is most effective and safe in reducing pain for the mother. These studies should also assess safety for the baby."
    },
    {
        "index": "cochrane-simplification-test-229",
        "sentence": "We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder. There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 litres, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I2 = 68%) were not statistically significant. Two studies indicated improved asthma control, but due to very significant heterogeneity (I2 = 98%) we did not pool data. No serious adverse events associated with yoga were reported, but the data on this outcome was limited. We found moderate-quality evidence that yoga probably leads to small improvements in quality of life and symptoms in people with asthma. There is more uncertainty about potential adverse effects of yoga and its impact on lung function and medication usage. RCTs with a large sample size and high methodological and reporting quality are needed to confirm the effects of yoga for asthma.",
        "gold": "We reviewed 15 studies that compared the effects of yoga with usual treatment or a 'sham' yoga in 1048 participants. We found that yoga probably improves quality of life and asthma symptoms to some extent. However, our confidence in the results is low as most of the studies were flawed in various ways. The effects of yoga on lung function were inconsistent, and we found a small amount of evidence indicating that yoga can reduce medication usage. Information on unwanted side effects was very limited; more studies are needed to assess this. High-quality studies involving large numbers of participants are required for us to be able to draw a firm conclusion about the effects of yoga for asthma."
    },
    {
        "index": "cochrane-simplification-test-230",
        "sentence": "The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta-1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) -0.06, 95% CI -0.15 to 0.03) between IFN beta-1a and placebo (moderate-quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate-quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low-quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re-analysis. Other comparisons were also reported in single trials. An open trial of anti-T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events. Trials of interferon beta-1a and MTX provided moderate-quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures.",
        "gold": "This review included 10 trials (249 participants). One of these trials (24 participants) is completed but has not yet been published. Seven trials compared treatments with placebo (inactive treatment): three of intravenous immunoglobulin (IVIg), two of interferon beta-1a (IFN beta-1a), and one each of oxandrolone, methotrexate (MTX), and arimoclomol (not yet published). A further two trials compared MTX with combined immunosuppressive therapy (MTX with anti-T lymphocyte immunoglobulin (ATG) (an agent that destroys white blood cells) and MTX with azathioprine). In these two trials, participants and investigators knew which treatment participants were receiving, which could have biased the results. For our primary outcome, which was muscle strength, we were only able to combine the results for the two trials of IFN beta-1a therapy versus placebo. This treatment did not appear to offer a benefit in terms of muscle strength. MTX also did not stop or retard loss of muscle strength when compared to placebo. We considered the evidence from these trials to be of moderate quality because the trials were too small to rule out a possible benefit for these drugs. For the other trials, the evidence was of very low quality. Three trials compared IVIg (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because the available data were not suitable. One trial of ATG combined with MTX versus MTX alone provided very low-quality evidence of an effect on muscle strength in favour of MTX plus ATG at 12 months. The other comparisons, of MTX versus placebo, oxandrolone versus placebo, azathioprine combined with MTX versus MTX, and arimoclomol versus placebo were reported in single trials that did not provide enough data for analysis of the effect on muscle strength. Due to their small size and short duration, the trials we studied were generally unable to give definitive answers as to whether the treatments tested were effective or ineffective. All of the interventions we studied had some adverse effects and are known to cause potentially serious adverse events. We need larger trials of longer duration, using robust ways of measuring the effects of treatments that are meaningful to people with IBM. Agreeing on common trial measurements will also make it easier to compare trial results and assess potential treatments. The evidence is current to October 2014."
    },
    {
        "index": "cochrane-simplification-test-231",
        "sentence": "No new trials were identified for this first update. We included nine RCTs (3144 participants). Linezolid was associated with a significantly better clinical (RR 1.09, 95% CI 1.03 to 1.16) and microbiological cure rate in adults (RR 1.08, 95% CI 1.01 to 1.16). For those infections due to MRSA, linezolid was significantly more effective than vancomycin in clinical (RR 1.09, 95% CI 1.03 to 1.17) and microbiological cure rates (RR 1.17, 95% CI 1.04 to 1.32). No RCT reported SSTI-related and treatment-related mortality. There was no significant difference in all-cause mortality between linezolid and vancomycin (RR 1.44, 95% CI 0.75 to 2.80). There were fewer incidents of red man syndrome (RR 0.04, 95% CI 0.01 to 0.29), pruritus (RR 0.36, 95% CI 0.17 to 0.75) and rash (RR 0.27, 95% CI 0.12 to 0.58) in the linezolid group compared with vancomycin, however, more people reported thrombocytopenia (RR 13.06, 95% CI 1.72 to 99.22), and nausea (RR 2.45, 95% CI 1.52 to 3.94) when treated with linezolid. It seems, from the available data, that length of stay in hospital was shorter for those in the linezolid group than the vancomycin group. The daily cost of outpatient therapy was less with oral linezolid than with intravenous vancomycin. Although inpatient treatment with linezolid cost more than inpatient treatment with vancomycin per day, the median length of hospital stay was three days shorter with linezolid. Thus, total hospital charges per patient were less with linezolid treatment than with vancomycin treatment. Linezolid seems to be more effective than vancomycin for treating people with SSTIs, including SSTIs caused by MRSA. The available evidence is at high risk of bias and is based on studies that were supported by the pharmaceutical company that makes linezolid. Further well-designed, independently-funded, RCTs are needed to confirm the available evidence.",
        "gold": "This review identified nine RCTs, with a total of 3144 participants, and compared treatment with linezolid against treatment with vancomycin for skin and soft tissue infections. No new trials were identified for this first update. Linezolid was found to be more effective than vancomycin for treating these infections. There were fewer skin complications in the group that were treated with linezolid. There were no differences between the two groups in the number of reported deaths, and those treated with linezolid had shorter lengths of hospital stay than those treated with vancomycin. The daily cost of outpatient therapy was less with oral linezolid than with intravenous vancomycin, although for inpatient treatment, linezolid was more expensive than vancomycin. Well-designed trials will be required in future to confirm these results, as the trials from which these conclusions were drawn were of poor methodological quality, at high risk of bias, and were funded by the pharmaceutical company that makes linezolid."
    },
    {
        "index": "cochrane-simplification-test-232",
        "sentence": "We included eight RCTs with a total of 512 participants. Our critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. Postoperative mortality (OR 0.64, 95% confidence interval (CI) 0.26 to 1.54; P = 0.32), overall survival (HR 0.84, 95% CI 0.61 to 1.16; P = 0.29), and morbidity showed no significant differences, except of delayed gastric emptying, which significantly favoured CW (OR 3.03, 95% CI 1.05 to 8.70; P = 0.04). Furthermore, we noted that operating time (MD -45.22 minutes, 95% CI -74.67 to -15.78; P = 0.003), intraoperative blood loss (MD -0.32 L, 95% CI -0.62 to -0.03; P = 0.03), and red blood cell transfusion (MD -0.47 units, 95% CI -0.86 to -0.07; P = 0.02) were significantly reduced in the PPW group. All significant results were associated with low-quality evidence based on GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. Current evidence suggests no relevant differences in mortality, morbidity, and survival between the two operations. However, some perioperative outcome measures significantly favour the PPW procedure. Given obvious clinical and methodological heterogeneity, future high-quality RCTs of complex surgical interventions based on well-defined outcome parameters are required.",
        "gold": "We included eight randomised controlled trials with a total of 512 participants in this review. The included trials revealed vast differences in sample size as well as clinical and methodological quality. We could identify no relevant differences in terms of main complications, long-term survival, or death due to complications after the operation, but operating time, intraoperative blood loss, and need for blood transfusion seem to be less frequent in the group treated with the pylorus-preserving Whipple operation. Our conclusion is that, at present, no relevant difference is evident between the two surgical procedures for the treatment of pancreatic or periampullary cancer. The quality of the body of evidence is still low since all trials revealed some shortcomings in terms of methodological quality or reporting."
    },
    {
        "index": "cochrane-simplification-test-233",
        "sentence": "Six RCTs involving 1862 participants were included. The effect of calcium channel blockers on the risk of death was reported in five of the RCTs. The pooled odds ratio (OR) for the five studies was 0.91 (95% confidence interval [95% CI] 0.70 to 1.16). For the five RCTs that reported death and severe disability (unfavourable outcome), the pooled OR 0.97 (95%CI 0.81 to 1.18). In the two RCTs which reported the risk of death in a subgroup of traumatic subarachnoid haemorrhage patients, the pooled OR 0.59 (95% CI 0.37 to 0.94). Three RCTs reported death and severe disability as an outcome in this subgroup, and the pooled OR 0.67 (95% CI 0.46 to 0.98). This systematic review of randomised controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.",
        "gold": "This review looked at all high quality trials comparing the use of calcium channel blockers with a control, in head-injured patients of any age. The authors also looked at trials involving patients suffering from subarachnoid haemorrhage (that is, bleeding into the space between the brain and the skull) caused by an injury, as a subgroup. The authors found six eligible trials involving 1862 patients. The results indicate that there is insufficient evidence to support the use of calcium channel blockers. The authors conclude that there is some evidence that a calcium channel blocker called nimodipine may be beneficial for some patients with subarachnoid haemorrhage. However, there is also an indication of certain adverse reactions amongst patients treated with nimodipine which may mean that the drug is harmful for some individuals. The authors recommend that the promising results in patients with subarachnoid haemorrhage are replicated in a larger well designed trial, before any firm conclusions about the effectiveness of the drug can be drawn. In future trials, data on outcomes other than death and severe disability, such as quality of life of the survivors and the economic utility of the drug, should be measured; such outcomes have not been considered in existing research."
    },
    {
        "index": "cochrane-simplification-test-234",
        "sentence": "We included four RCTs with a total of 3090 enrolled participants (one study used a cluster-randomized design). Three trials were considered to have a relatively low risk of bias, and one trial was considered to have a relatively high risk. When survival to hospital discharge was compared, 38 of 320 (11.88%) participants survived to discharge in the initial CPR plus delayed defibrillation group compared with 39 of 338 participants (11.54%) in the immediate defibrillation group (RR 1.09, 95% CI 0.54 to 2.20, Chi2 = 10.78, degrees of freedom (df) = 5, P value 0.06, I2 = 54%, low-quality evidence). When we compared the neurological outcome at hospital discharge (RR 1.12, 95% CI 0.65 to 1.93, low-quality evidence), the rate of return of spontaneous circulation (ROSC) (RR 0.94, 95% CI 0.77 to 1.15,low-quality evidence) and survival at one year (RR 0.77, 95% CI 0.24 to 2.49, low-quality evidence), we could not rule out the superiority of either treatment. Adverse effects were not associated with either treatment. Owing to the low quality of available evidence, we have been unable to determine conclusively whether immediate defibrillation and one and one-half to three minutes of CPR as initial therapy before defibrillation have similar effects on rates of return of spontaneous circulation, survival to discharge or neurological insult. We have also been unable to conclude whether either treatment approach provides a degree of superiority in OHCA. We propose that this is an area that needs further rigorous research through additional high-quality RCTs, including larger sample sizes and proper subgroup analysis.",
        "gold": "After reviewing the studies and their available data, we could not be certain that one approach had superiority over another, and we could not establish whether the two treatments had similar effects on outcomes. We found no adverse effects associated with either treatment. Currently, no definitive evidence allows us to conclude that chest compressions should be the initial therapy for patients with OHCA over immediate electric shock treatment. However, we believe that the amount and quality of research in this area currently are not sufficient to allow strong conclusions. To further our understanding of the efficacy of these two different strategies, further rigorous randomized controlled trials are required."
    },
    {
        "index": "cochrane-simplification-test-235",
        "sentence": "The new search identified fifteen trials. Three trials were eligible for inclusion. Ten trials involving eight different comparison groups have been included. Only one trial reported live birth rates. The number of oocytes retrieved were significantly less in the conventional GnRHa long protocol compared to stop protocol and GnRH antagonist protocol. Total dose of gonadotrophins used was significantly higher in the GnRHa long protocol group compared to the Stop protocol and GnRH antagonist groups. Cancellation rates were significantly higher in the GnRHa flare up group compared to the GnRHa long protocol group. None of the studies reported a difference in the miscarriage and ectopic pregnancy rates. There is insufficient evidence to support the routine use of any particular intervention either for pituitary down regulation, ovarian stimulation or adjuvant therapy in the management of poor responders to controlled ovarian stimulation in IVF. More robust data from good quality RCTs with relevant outcomes are needed.",
        "gold": "This review of ten randomised controlled trials suggests there is insufficient evidence to support the routine use of any one particular intervention in the management of women who are poor responders. More research is needed with good quality trials looking at relevant outcomes such as live birth rates rather than treatment-associated outcomes such as positive pregnancy rates or number of eggs. Research is also recommended in adverse outcomes and costs of these treatments."
    },
    {
        "index": "cochrane-simplification-test-236",
        "sentence": "This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality. Further data from trials that describe the methods of randomisation, test the blindness of the study evaluators, and implement the CONSORT guidelines would enable greater confidence in these findings.",
        "gold": "Studies were conducted in Europe, Asia and North America with packages of family intervention varying among studies, although there were no clear differences in study design. Results indicated that family intervention may reduce the risk of relapse and improve compliance with medication. However data were often inadequately reported and therefore unusable. As this package of care is widely employed, there should be further research to properly clarify several of the short-term and long-term outcomes."
    },
    {
        "index": "cochrane-simplification-test-237",
        "sentence": "Three trials that randomized a combined total of 263 participants met the review inclusion criteria. All three trials examined the treatment of symptomatic in-stent restenosis within the femoropopliteal arteries. These trials were carried out in Germany and Austria and used paclitaxel as the agent in the drug-eluting balloons. Two of the three trials were industry sponsored. Two companies manufactured the drug-eluting balloons (Eurocor, Bonn, Germany; Medtronic, Fridley, Minnesota, USA). The trials examined both anatomical and clinical endpoints. We noted heterogeneity in the frequency of bailout stenting deployment between studies as well as in the dosage of paclitaxel applied by the DEBs. Using GRADE assessment criteria, we determined that the certainty of evidence presented was very low for the outcomes of amputation, target lesion revascularization, binary restenosis, death, and improvement of one or more Rutherford categories. Most participants were followed up to 12 months, but one trial followed participants for up to 24 months. Trial results show no difference in the incidence of amputation between DEBs and uncoated balloon angioplasty. DEBs showed better outcomes for up to 24 months for target lesion revascularization (odds ratio (OR) 0.05, 95% confidence Interval (CI) 0.00 to 0.92 at six months; OR 0.24, 95% CI 0.08 to 0.70 at 24 months) and at six and 12 months for binary restenosis (OR 0.28, 95% CI 0.14 to 0.56 at six months; OR 0.34, 95% CI 0.15 to 0.76 at 12 months). Participants treated with DEBs also showed improvement of one or more Rutherford categories at six and 12 months (OR 1.81, 95% CI 1.02 to 3.21 at six months; OR 2.08, 95% CI 1.13 to 3.83 at 12 months). Data show no clear differences in death between DEBs and uncoated balloon angioplasty. Data were insufficient for subgroup or sensitivity analyses to be conducted. Based on a meta-analysis of three trials with 263 participants, evidence suggests an advantage for DEBs compared with uncoated balloon angioplasty for anatomical endpoints such as target lesion revascularization (TLR) and binary restenosis, and for one clinical endpoint - improvement in Rutherford category post intervention for up to 24 months. However, the certainty of evidence for all these outcomes is very low due to the small number of included studies and participants and the high risk of bias in study design. Adequately powered and carefully constructed randomized controlled trials are needed to adequately investigate the role of drug-eluting technologies in the management of in-stent restenosis.",
        "gold": "Our review included three clinical trials that randomized 263 participants (most recent search - November 28, 2017). Trials included leg arteries at and above the knee and were carried out in Europe; all used DEBs that contained the chemical known as \"paclitaxel.\" Two companies manufactured the DEBs: Eurocor and Medtronic. Most study participants were followed for six or more months; this is called \"follow-up.\" Results showed that DEBs were not better for participants than uncoated balloon angioplasty with regard to the need for amputation. At 24 months of follow-up, DEBs were associated with fewer target lesion revascularizations, which refers to the need to perform a procedure on a stent that had already been treated with a DEB or an uncoated balloon angioplasty for in-stent restenosis. DEBs were also found to have better binary restenosis rates, which refers to the percentage of treated stents that develop new stenosis after they have been treated with a DEB or an uncoated balloon angioplasty. Finally, more people who were treated with DEBs described improvement in their leg symptoms, as measured by a change in their Rutherford category. DEBs were not found to be better for participants than uncoated balloon angioplasty with regard to patient death. The certainty of the evidence presented was very low because we identified only three studies with small numbers of participants, and because many participants in those studies were lost to follow-up. Furthermore, risk of performance and attrition bias was significant, as was risk of other biases, due to lack of accounting for the type of stent treated and the need for bailout stenting."
    },
    {
        "index": "cochrane-simplification-test-238",
        "sentence": "Seven trials consisting of 922 participants were included in this analysis. Trials ranged from 32 to 242 participants. On pooled analysis, corticosteroids reduced the subsequent occurrence of coronary artery abnormalities (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.18 to 0.46; 907 participants; 7 studies; I\u00b2 = 55%) without resultant serious adverse events (no events, 737 participants) and mortality (no events, 915 participants). In addition, corticosteroids reduced the duration of fever (mean difference (MD) \u22121.65 days, 95% CI \u22123.31 to 0.00; 210 participants; 2 studies; I\u00b2 = 88%), time for laboratory parameters (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) to normalise (MD \u22122.80 days, 95% CI \u22124.38 to \u22121.22; 178 participants; 1 study) and length of hospital stay (MD \u22121.41 days, 95% CI \u22122.36 to \u22120.46; 39 participants; 1 study). No studies detailed outcomes beyond 24 weeks. Subgroup analysis showed some potential groups that may benefit more than others; however, further randomised controlled trials are required before this can be the basis for clinical action. Evidence quality was graded according to the GRADE system. Evidence was considered high quality for the incidence of serious adverse events, mortality and time for laboratory parameters to normalise. Evidence was considered moderate for the incidence of coronary artery abnormalities due to potential inconsistencies in data geography and patient benefits according to grouping. Evidence was moderate for duration of clinical symptoms (fever, rash) due to potential subjectivity in measurement. Evidence was moderate for length of hospital stay as only one study recorded this outcome. This means that we are reasonably confident that the true effect is close to that estimated in this work. Moderate-quality evidence shows that use of steroids in the acute phase of KD can be associated with improved coronary artery abnormalities, shorter duration of hospital stay and a decreased duration of clinical symptoms. High-quality evidence shows reduced inflammatory marker levels. There were insufficient data available regarding incidence of adverse effects attributable to steroids, mortality and long-term (> 1 year) coronary morbidity. Certain groups, including those based in Asia, those with higher risk scores, and those receiving longer steroid treatment may have greater benefit from steroid use, especially with decreasing rates of heart problems, but more tests are needed to answer these questions. Evidence presented in this study suggests that treatment with a long course of steroids should be considered for all children diagnosed with KD until further studies are performed.",
        "gold": "Evidence is current to November 2016. Male and female children diagnosed with Kawasaki disease were included in this review. We selected only randomised clinical trials. Trials compared the use of steroids against not using steroids. This review involves seven trials and 922 participants. Steroids appear to reduce the risk of heart problems after Kawasaki disease without causing any important side effects. They also reduce the length of symptoms (fever and rash), length of hospital stay, and blood markers associated with being unwell. Certain groups, including those based in Asia, those with higher risk scores, and those receiving longer steroid treatment, may have greater benefit from steroid use, especially with decreasing rates of heart problems, but more tests are needed to answer these questions. More tests are also needed to obtain a more accurate marker of the risk of serious side effects and to determine if there is a lower chance of death when using steroids. Evidence presented in this review suggests that treatment with a long course of steroids should be considered for all children diagnosed with Kawasaki disease until further studies are performed. Evidence quality was graded according to the GRADE system. Evidence was considered high quality for serious adverse events, mortality and time for laboratory parameters to normalise. Evidence was considered moderate quality for the risk of future heart problems, duration of clinical symptoms (fever, rash) and length of hospital stay. This means that we are reasonably confident that the true effect is close to that estimated in this work."
    },
    {
        "index": "cochrane-simplification-test-239",
        "sentence": "We included eight studies comprising 846 randomised participants, of which four studies involved comparisons of PIP with control groups only. Four studies involved comparisons with another treatment group (i.e. another PIP, video-interaction guidance, psychoeducation, counselling or cognitive behavioural therapy (CBT)), two of these studies included a control group in addition to an alternative treatment group. Samples included women with postpartum depression, anxious or insecure attachment, maltreated, and prison populations. We assessed potential bias (random sequence generation, allocation concealment, incomplete outcome data, selective reporting, blinding of participants and personnel, blinding of outcome assessment, and other bias). Four studies were at low risk of bias in four or more domains. Four studies were at high risk of bias for allocation concealment, and no study blinded participants or personnel to the intervention. Five studies did not provide adequate information for assessment of risk of bias in at least one domain (rated as unclear). Six studies contributed data to the PIP versus control comparisons producing 19 meta-analyses of outcomes measured at post-intervention or follow-up, or both, for the primary outcomes of parental depression (both dichotomous and continuous data); measures of parent-child interaction (i.e. maternal sensitivity, child involvement and parent engagement; infant attachment category (secure, avoidant, disorganised, resistant); attachment change (insecure to secure, stable secure, secure to insecure, stable insecure); infant behaviour and secondary outcomes (e.g. infant cognitive development). The results favoured neither PIP nor control for incidence of parental depression (RR 0.74, 95% CI 0.52 to 1.04, 3 studies, 278 participants, low quality evidence) or parent-reported levels of depression (SMD -0.22, 95% CI -0.46 to 0.02, 4 studies, 356 participants, low quality evidence). There were improvements favouring PIP in the proportion of infants securely attached at post-intervention (RR 8.93, 95% CI 1.25 to 63.70, 2 studies, 168 participants, very low quality evidence); a reduction in the number of infants with an avoidant attachment style at post-intervention (RR 0.48, 95% CI 0.24 to 0.95, 2 studies, 168 participants, low quality evidence); fewer infants with disorganised attachment at post-intervention (RR 0.32, 95% CI 0.17 to 0.58, 2 studies, 168 participants, low quality evidence); and an increase in the proportion of infants moving from insecure to secure attachment at post-intervention (RR 11.45, 95% CI 3.11 to 42.08, 2 studies, 168 participants, low quality evidence). There were no differences between PIP and control in any of the meta-analyses for the remaining primary outcomes (i.e. adverse effects), or secondary outcomes. Four studies contributed data at post-intervention or follow-up to the PIP versus alternative treatment analyses producing 15 meta-analyses measuring parent mental health (depression); parent-infant interaction (maternal sensitivity); infant attachment category (secure, avoidant, resistant, disorganised) and attachment change (insecure to secure, stable secure, secure to insecure, stable insecure); infant behaviour and infant cognitive development. None of the remaining meta-analyses of PIP versus alternative treatment for primary outcomes (i.e. adverse effects), or secondary outcomes showed differences in outcome or any adverse changes. We used the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) approach to rate the overall quality of the evidence. For all comparisons, we rated the evidence as low or very low quality for parental depression and secure or disorganised infant attachment. Where we downgraded the evidence, it was because there was risk of bias in the study design or execution of the trial. The included studies also involved relatively few participants and wide CI values (imprecision), and, in some cases, we detected clinical and statistical heterogeneity (inconsistency). Lower quality evidence resulted in lower confidence in the estimate of effect for those outcomes. Although the findings of the current review suggest that PIP is a promising model in terms of improving infant attachment security in high-risk families, there were no significant differences compared with no treatment or treatment-as-usual for other parent-based or relationship-based outcomes, and no evidence that PIP is more effective than other methods of working with parents and infants. Further rigorous research is needed to establish the impact of PIP on potentially important mediating factors such as parental mental health, reflective functioning, and parent-infant interaction.",
        "gold": "We searched electronic databases and identified randomised controlled trials (RCTs, where participants are randomly allocated to one of two or more treatment groups) and one cluster randomised trial (where prisons rather than participants were used as the unit of randomisation), in which participants had been allocated to a receive PIP versus a control group, and which reported results using at least one standard measure of outcome (i.e. an instrument which has been tested to ensure that it reliably measures the outcome under investigation). Evidence is current to 13 January 2014. We identified eight studies with 846 randomised participants comparing either PIP with a no-treatment control group (four studies) or comparing PIP with other types of treatment (four studies). The studies comparing PIP with a no-treatment control group contributed data to 19 meta-analyses of the primary outcomes of parental mental health (depression), parent-infant interaction outcomes of maternal sensitivity (i.e. the extent to which the caregiver responds in a timely and attuned manner), child involvement and parent positive engagement, and infant outcomes of infant attachment category (the infant's ability to seek and maintain closeness to primary caregiver - infant attachment is classified as follows: 'secure' infant attachment is a positive outcome, which indicates that the infant is able to be comforted when distressed and is able to use the parent as a secure base from which to explore the environment. Infants who are insecurely attached are either 'avoidant' (i.e. appear not to need comforting when they are distressed and attempt to manage the distress themselves); or 'resistant' (i.e. unable to be comforted when distressed and alternate between resistance and anger). Children who are defined as \u2018disorganised\u2019 are unable to produce a coherent strategy in the face of distress and produce behaviour that is a mixture of approach and avoidance to the caregiver); and the secondary outcomes of infant behaviour and infant cognitive development (i.e. intellectual development, including thinking, problem solving and communicating). In our analyses, parents who received PIP were more likely to have an infant who was securely emotionally attached to the parent after the intervention; this a favourable outcome but there is very low quality evidence to support it. The studies comparing PIP with another model of treatment contributed data to 15 meta-analysis assessments of primary outcomes, including parental mental health, parent-infant interaction (maternal sensitivity); infant attachment and infant behaviour, or secondary infant outcomes such as infant cognitive development. None of these comparisons showed differences that favoured either PIP or the alternative intervention. None of the comparisons of PIP with either a control or comparison treatment group showed adverse changes for any outcome. We conclude that although PIP appears to be a promising method of improving infant attachment security, there is no evidence about its benefits in terms of other outcomes, and no evidence to show that it is more effective than other types of treatment for parents and infants. Further research is needed. The included studies were unclear about important quality criteria, had limitations in terms of their design or methods, or we judged that there was risk of bias in the trial. This lower quality evidence gives us less confidence in the observed effects."
    },
    {
        "index": "cochrane-simplification-test-240",
        "sentence": "We found one new included study in this updated version. In total, our updated review includes 11 trials (with 753 participants). The low quality of evidence showed no significant differences in average Apgar scores at one minute (N = six trials, 519 participants; 95% confidence (CI) -0.16 to 0.31, P = 0.53) and at five minutes (N = six trials, 519 participants; 95% CI -0.06 to 0.06, P = 0.98). None of the 11 trials reported maternal desaturation. The very low quality of evidence showed that in comparison to room air, women in labour receiving supplementary oxygen had higher maternal oxygen saturation (N = three trials, 209 participants), maternal PaO2 (oxygen pressure in the blood; N = six trials, 241 participants), UaPO2 (foetal umbilical arterial blood; N = eight trials, 504 participants; 95% CI 1.8 to 4.9, P < 0.0001) and UvPO2 (foetal umbilical venous blood; N = 10 trials, 683 participants). There was high heterogeneity among these outcomes. A subgroup analysis showed no significant difference in UaPO2 between the two intervention groups in low-risk studies, whereas the high-risk studies showed a benefit for the neonatal oxygen group. Overall, we found no convincing evidence that giving supplementary oxygen to healthy term pregnant women during elective caesarean section under regional anaesthesia is either beneficial or harmful for either the mother or the foetus' short-term clinical outcome as assessed by Apgar scores. Although, there were significant higher maternal and neonatal blood gas values and markers of free radicals when extra oxygen was given, the results should be interpreted with caution due to the low grade quality of the evidence.",
        "gold": "This updated Cochrane review included 11 studies involving 753 participants. The studies compared maternal (mother) and neonatal (foetal) outcomes when pregnant women received extra oxygen versus room air. Oxygen was given to the women in different ways (at any flow rate or concentration via any oxygen delivery device). Overall, the results of this updated review reach the same conclusions as the original published review. None of the 11 included trials reported maternal desaturation. No differences were noted in routine measures of foetal wellbeing (Apgar scores) when mothers who received extra oxygen were compared with those who did not. The pregnant women receiving extra oxygen in comparison with room air had significantly higher oxygen saturation (three trials) and partial pressure of oxygen in arterial blood (five trials), as well as a significantly higher partial pressure of oxygen in both the umbilical artery and the umbilical vein (eight and 11 trials, respectively). Two trials reported higher markers of free radicals (perhaps indicating stress from excess oxygen) in mothers and foetuses when extra oxygen was given, but this is of no clinical significance Overall, we found no convincing evidence that giving oxygen in this situation is either beneficial or harmful for either the mother or the foetus. None of the 11 studies focused on maternal changes in oxygen saturation (defined as maternal saturation less than 90%). We graded the quality of evidence as low for the primary outcome (Apgar scores), and very low for the secondary outcomes (maternal oxygen saturation; partial pressure of oxygen in arterial blood, the umbilical artery and the umbilical vein). The reasons for our grading were risk of bias and inconsistency of the results."
    },
    {
        "index": "cochrane-simplification-test-241",
        "sentence": "We included twelve studies containing data on 2196 participants; four of these studies were newly included in this 2011 update of our 2006 Cochrane review. Six intervention groups in four trials provided data on the percentage of pills taken. Reminder packaging increased the percentage of pills taken (mean difference (MD) 11% (95% confidence interval (CI) 6% to 17%)). Notable heterogeneity occurred among these trials (I2 = 96.3%). Two trials provided data for the proportion of self-reported adherent patients, reporting a reduction in the intervention group which was not statistically significant (odds ratio = 0.89 (95% CI 0.56 to 1.40)). We conducted meta-analysis on data from two trials assessing the effect of reminder packaging on blood pressure measurements. We found that reminder packaging significantly decreased diastolic blood pressure (MD = -5.89 mmHg (95% CI -6.70 to -5.09; P < 0.00001; I2 = 0%). No effect was seen on systolic blood pressure (mean change -1.01, 95% CI -2.22 to 0.20; P = 0.1, I2 = 0%). We also conducted meta-analysis on extracted data from two trials that looked at change in glycated haemoglobin. We found that reminder packaging significantly reduced glycated haemoglobin levels (MD -0.72; 95% CI -0.83 to -0.60; P < 0.00001; I2 = 92%), although there was considerable heterogeneity. No appropriate data were available for meta-analysis of remaining clinical outcomes, which included serum vitamin C and E levels, and self-reported psychological symptoms (one trial each). We reported remaining data narratively. In one study the presence of a reminder packaging aid was found to be preferred by patients with low literacy levels. Reminder packing may represent a simple method for improving adherence for patients with selected conditions. Further research is warranted to improve the design and targeting of these devices.",
        "gold": "We assessed twelve studies involving 2196 participants who were taking self-administered medications for at least one month. The studies involved different types of packaging, and different medications for various health problems. We found that reminder packaging increased the proportion of people taking their medications when measured by pill count; however, this effect was not large. We also found some evidence that reminder packaging may be beneficial in improving clinical outcomes such as blood pressure. Reminder packing for certain individuals may represent a simple method for improving the adherence to medications; further research is needed to improve the design and targeting of these devices."
    },
    {
        "index": "cochrane-simplification-test-242",
        "sentence": "We identified a total of 15 randomised trials evaluating 11 different pharmacological interventions (methylprednisolone, multivitamin antioxidant infusion, vitamin E infusion, amrinone, prostaglandin E1, pentoxifylline, mannitol, trimetazidine, dextrose, allopurinol, and OKY 046 (a thromboxane A2 synthetase inhibitor)). All trials had high risk of bias. There were no significant differences between the groups in mortality, liver failure, or perioperative morbidity. The trimetazidine group had a significantly shorter hospital stay than control (MD -3.00 days; 95% CI -3.57 to -2.43). There were no significant differences in any of the clinically relevant outcomes in the remaining comparisons. Methylprednisolone improved the enzyme markers of liver function and trimetazidine, methylprednisolone, and dextrose reduced the enzyme markers of liver injury compared with controls. However, there is a high risk of type I and type II errors because of the few trials included, the small sample size in each trial, and the risk of bias. Trimetazidine, methylprednisolone, and dextrose may protect against ischaemia reperfusion injury in elective liver resections performed under vascular occlusion, but this is shown in trials with small sample sizes and high risk of bias. The use of these drugs should be restricted to well-designed randomised clinical trials before implementing them in clinical practice.",
        "gold": "In experimental studies many drugs have shown some promise in decreasing liver damage caused by the occluded blood supply. We identified a total of 15 randomised trials evaluating 11 different pharmacological interventions (methylprednisolone, multivitamin antioxidant infusion, vitamin E infusion, amrinone, prostaglandin E1, pentoxifylline, mannitol, trimetazidine, dextrose, allopurinol, and OKY 046). All trials had risk of bias ('systematic errors') and risk of play of chance ('random errors'). There was no significant difference between the groups in mortality, liver failure, or post-operative complications. The trimetazidine group had a significantly shorter hospital stay, and the vitamin E group had a significantly shorter intensive therapy unit stay than the respective controls. There was no significant difference in any of the clinically relevant outcomes in the remaining comparisons. Methylprednisolone improved the enzyme markers of liver function and trimetazidine, methylprednisolone, and dextrose reduced the enzyme markers of liver injury compared to controls. However, there is a high risk of type I (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included, the small sample size in each trial, and the risks of bias. Three pharmacological drugs - trimetazidine, methylprednisolone, and dextrose - have potential for a protective role against liver injury in elective liver surgery involving blood supply occlusion. However, based on the current evidence it is recommended that the use of these agents should be restricted to well-designed trials in patients undergoing resection."
    },
    {
        "index": "cochrane-simplification-test-243",
        "sentence": "Apart from the remaining 37 studies included from the original review, the search resulted in the inclusion of 24 new studies. In total, we included 61 studies; 46 for prevalence, six for both prevalence and risk factors, and nine not meeting the inclusion criteria, but assessing risk factors. The 52 studies evaluating the prevalence of renal dysfunction included 13,327 participants of interest, of whom at least 4499 underwent renal function testing. The prevalence of adverse renal effects ranged from 0% to 84%. This variation may be due to diversity of included malignancies, received treatments, reported outcome measures, follow-up duration and the methodological quality of available evidence. Seven out of 52 studies, including 244 participants, reported the prevalence of chronic kidney disease, which ranged from 2.4% to 32%. Of these 52 studies, 36 studied a decreased (estimated) GFR, including at least 432 CCS, and found it was present in 0% to 73.7% of participants. One eligible study reported an increased risk of glomerular dysfunction after concomitant treatment with aminoglycosides and vancomycin in CCS receiving total body irradiation (TBI). Four non-eligible studies assessing a total cohort of CCS, found nephrectomy and (high-dose (HD)) ifosfamide as risk factors for decreased GFR. The majority also reported cisplatin as a risk factor. In addition, two non-eligible studies showed an association of a longer follow-up period with glomerular dysfunction. Twenty-two out of 52 studies, including 851 participants, studied proteinuria, which was present in 3.5% to 84% of participants. Risk factors, analysed by three non-eligible studies, included HD cisplatin, (HD) ifosfamide, TBI, and a combination of nephrectomy and abdominal radiotherapy. However, studies were contradictory and incomparable. Eleven out of 52 studies assessed hypophosphataemia or tubular phosphate reabsorption (TPR), or both. Prevalence ranged between 0% and 36.8% for hypophosphataemia in 287 participants, and from 0% to 62.5% for impaired TPR in 246 participants. One non-eligible study investigated risk factors for hypophosphataemia, but could not find any association. Four out of 52 studies, including 128 CCS, assessed the prevalence of hypomagnesaemia, which ranged between 13.2% and 28.6%. Both non-eligible studies investigating risk factors identified cisplatin as a risk factor. Carboplatin, nephrectomy and follow-up time were other reported risk factors. The prevalence of hypertension ranged from 0% to 50% in 2464 participants (30/52 studies). Risk factors reported by one eligible study were older age at screening and abdominal radiotherapy. A non-eligible study also found long follow-up time as risk factor. Three non-eligible studies showed that a higher body mass index increased the risk of hypertension. Treatment-related risk factors were abdominal radiotherapy and TBI, but studies were inconsistent. Because of the profound heterogeneity of the studies, it was not possible to perform meta-analyses. Risk of bias was present in all studies. The prevalence of adverse renal effects after treatment with cisplatin, carboplatin, ifosfamide, radiation therapy involving the kidney region, nephrectomy, or any combination of these, ranged from 0% to 84% depending on the study population, received treatment combination, reported outcome measure, follow-up duration and methodological quality. With currently available evidence, it was not possible to draw solid conclusions regarding the prevalence of, and treatment-related risk factors for, specific adverse renal effects. Future studies should focus on adequate study designs and reporting, including large prospective cohort studies with adequate control groups when possible. In addition, these studies should deploy multivariable risk factor analyses to correct for possible confounding. Next to research concerning known nephrotoxic therapies, exploring nephrotoxicity after new therapeutic agents is advised for future studies. Until more evidence becomes available, CCS should preferably be enrolled into long-term follow-up programmes to monitor their renal function and blood pressure.",
        "gold": "The evidence is current to March 2017. We included 61 studies; 46 on prevalence, six for both prevalence and risk factors, and nine studies that did not meet all the requirements for this review, but evaluated risk factors (non-eligible studies). Participants in the studies had been treated before the age of 21 years with chemotherapy (i.e. cisplatin, carboplatin, ifosfamide), radiation, or surgery involving the kidneys, or a combination of these treatments. The studies took place at least one year after the participants had finished their treatment. The 52 studies that evaluated prevalence of adverse kidney effects included 13,327 participants, of whom 4499 underwent kidney function tests. The studies were very different from each other, in the types of participants and treatments, length of follow-up and how they measured treatment results, and their methods were of variable quality. The percentage of CCS with kidney problems ranged from 0% to 84%. Reported risk factors were often inconsistent among studies. The prevalence of chronic kidney disease ranged from 2.4% to 32% in 244 participants (7/52 studies). Thirty-six out of 52 studies, including at least 432 participants, carried out a kidney function test called glomerular filtration rate (GFR). An abnormal GFR was found to be present in 0% to 73.7% of participants. One eligible study found an increased risk of abnormal GFR in participants who had been treated with total body irradiation (TBI) and received certain types of antibiotics (aminoglycosides and vancomycin). Four non-eligible studies reported an increased risk of abnormal GFR for participants treated with surgery of the kidney and ifosfamide. Some studies also reported that cisplatin and long follow-up duration were risk factors. Twenty-two out of 52 studies, including 851 participants, assessed an abnormal amount of proteins in the urine, which they found in 3.5% to 84% of participants. Risk factors, evaluated by three non-eligible studies, included cisplatin, ifosfamide, TBI, and a combination of surgery and radiation involving the kidney. However, the results of these studies did not agree, and we could not analyse their results together because they used different definitions. Eleven out of 52 studies looked at a low level of phosphate in the blood (hypophosphataemia), or problems with the reabsorption of phosphate by the kidneys in 246 participants. Prevalence of hypophosphataemia ranged between 0% and 36.8% in 287 participants. The studies found problems with the reabsorption of phosphate by the kidneys in 0% to 62.5% of participants. One non-eligible study investigated risk factors, but could not find any association with hypophosphataemia. Four out of 52 studies, including 128 CCS, evaluated a low level of magnesium in the blood (hypomagnesaemia). Prevalence ranged between 13.2% and 28.6%. Two non-eligible studies identified cisplatin as risk factor for hypomagnesaemia. Other reported risk factors were carboplatin, surgery of the kidney, and follow-up time. However, studies were contradictory. The prevalence of high blood pressure ranged from 0% to 50% in 2464 participants (30/52 studies). Risk factors reported by one eligible study were older age at screening and radiation involving the kidney. A high body mass index was reported as a risk factor by three non-eligible studies. Other reported risk factors included follow-up time, and radiation involving the kidney or TBI. However, studies were contradictory. All studies showed problems that could affect our confidence in their results. More, and especially higher-quality research is needed to gain better insight into kidney adverse effects and related risk factors."
    },
    {
        "index": "cochrane-simplification-test-244",
        "sentence": "Two trials (182 participants) and two phytomedicines Niprisan\u00ae (also known as Nicosan\u00ae) and Ciklavit\u00ae were included. The Phase IIB (pivotal) trial suggests that Niprisan\u00ae was effective in reducing episodes of severe painful sickle cell disease crisis over a six-month period (low-quality evidence). It did not affect the risk of severe complications or the level of anaemia (low-quality evidence). No serious adverse effects were reported. The single trial of Cajanus cajan (Ciklavit\u00ae) reported a possible benefit to individuals with painful crises (low-quality evidence), and a possible adverse effect (non-significant) on the level of anaemia (low-quality evidence). While Niprisan\u00ae appeared to be safe and effective in reducing severe painful crises over a six-month follow-up period, further trials are required to assess its role in the management of people with sickle cell disease and the results of its multicentre trials are awaited. Currently no conclusions can be made regarding the efficacy of Ciklavit\u00ae. Based on the published results for Niprisan\u00ae and in view of the limitations in data collection and analysis of both trials, phytomedicines may have a potential beneficial effect in reducing painful crises in sickle cell disease. This needs to be further validated in future trials. More trials are required on the safety and efficacy of phytomedicines used in managing sickle cell disease.",
        "gold": "Two trials (182 participants) and two phytomedicines Niprisan\u00ae (also known as Nicosan\u00ae) and Ciklavit\u00ae were included. This review found that Niprisan\u00ae may help to reduce episodes of sickle cell disease crises associated with severe pain. Ciklavit\u00ae, which has been reported to reduce painful crises in people with sickle cell disease, deserves further study before recommendations can be made regarding its use. The trial of Ciklavit\u00ae also reported a possible adverse effect on the level of anaemia. Both formulations reported no serious adverse symptoms or derangement of liver or kidney function in the participants. More detailed and larger trials of these medicines will need to be carried out before we can make any recommendations about their use. Further research should also assess long-term outcome measures. We judged the quality of the evidence from this review to be of low to very low quality, depending on the outcome measured."
    },
    {
        "index": "cochrane-simplification-test-245",
        "sentence": "Our search strategies led to 308 potentially relevant references. From these, we included three studies involving 1999 participants. We judged the overall potential risk of bias as moderate. The studies were reported as RCTs; blinding was not reported, but given the study design it is likely that there was no blinding. One study was published in abstract form only; hence, detailed assessment of the risk of bias was not possible. Two trials compared standard treatment (chemotherapy plus radiotherapy) with PET-adapted therapy (chemotherapy only) in individuals with early-stage HL and negative PET scans. The study design of the third trial was more complex. Participants with early-stage HL were divided into those with a favourable or unfavourable prognosis. They were then randomised to receive PET-adapted or standard treatment. Following a PET scan, participants were further divided into PET-positive and PET-negative groups. To date, data have been published for the PET-negative arms only, making it possible to perform a meta-analysis including all three trials. Of the 1999 participants included in the three trials only 1480 were analysed. The 519 excluded participants were either PET-positive, or were excluded because they did not match the inclusion criteria. One study reported no deaths. The other two studies reported two deaths in participants receiving PET-adapted therapy and two in participants receiving standard therapy (very-low-quality evidence). Progression-free survival was shorter in participants with PET-adapted therapy (without radiotherapy) than in those receiving standard treatment with radiotherapy (HR 2.38; 95% CI 1.62 to 3.50; P value < 0.0001). This difference was also apparent in comparisons of participants receiving no additional radiotherapy (PET-adapted therapy) versus radiotherapy (standard therapy) (HR 1.86; 95% CI 1.07 to 3.23; P value = 0.03) and in those receiving chemotherapy but no radiotherapy (PET-adapted therapy) versus standard radiotherapy (HR 3.00; 95% CI 1.75 to 5.14; P value < 0.0001) (moderate-quality evidence). Short-term AEs only were assessed in one trial, which showed no evidence of a difference between the treatment arms (RR 0.91; 95% CI 0.54 to 1.53; P value = 0.72) (very-low-quality evidence). No data on long-term AEs were reported in any of the trials. To date, no robust data on OS, response rate, TRM, QoL, or short- and long-term AEs are available. However, this systematic review found moderate-quality evidence that PFS was shorter in individuals with early-stage HL and a negative PET scan receiving chemotherapy only (PET-adapted therapy) than in those receiving additional radiotherapy (standard therapy). More RCTs with longer follow ups may lead to more precise results for AEs, TRM and QoL, and could evaluate whether this PFS advantage will translate into an overall survival benefit. It is still uncertain whether PET-positive individuals benefit from PET-based treatment adaptation and the effect of such an approach in those with advanced HL.",
        "gold": "We searched important medical databases such as the Cochrane Central Register of Controlled Trials and MEDLINE. Two review authors independently screened, summarised and analysed the results. This lead to the inclusion of three randomised controlled trials (RCTs) with 1999 participants. Currently, only data for 1480 of these participants have been published and were included in this systematic review. Participants were randomised to receive either standard therapy (chemotherapy followed by radiotherapy) or PET-adapted therapy (chemotherapy only). The median age of participants was 32 years and 52% were male. The evidence provided is current to September 2014. We are unable to draw conclusions about the effect of PET-adapted therapy on OS as there was insufficient data available (4 deaths in 1480 participants). However, PFS was shorter following PET-adapted therapy than with standard treatment. Based on our data, we can assume that of 1000 individuals receiving PET-adapted treatment over 4 years, 222 individuals would experience disease progression or death compared with 100 of 1000 individuals receiving standard treatment. Only one trial reported on short-term adverse events and the findings were uncertain and do not provide reliable evidence. The studies did not provide any information on the outcomes of QoL, response to therapy or treatment-related mortality. We judged the quality of evidence for the outcomes of OS and adverse events as very low. We considered the quality of evidence for PFS to be moderate. To date, no robust data on OS are available. This systematic review shows that individuals with early-stage HL have a shorter PFS after PET-adapted therapy compared with those who receive standard therapy. More RCTs with longer follow ups may lead to more information on adverse events, treatment-related mortality and QoL, and could evaluate whether the PFS advantage seen with standard therapy will translate into a benefit in terms of OS."
    },
    {
        "index": "cochrane-simplification-test-246",
        "sentence": "We found 31 trials that met the inclusion criteria. No new trials were eligible in 2014. Twenty-one trials compared combined oral contraceptives (COCs); others examined different COC regimens, progestin-only pills, injectables, a vaginal ring, and implants. None included a placebo. Of 34 comparisons, eight had any notable difference between the study groups in an outcome. Twelve trials studied desogestrel-containing COCs, and the few differences from levonorgestrel COCs were inconsistent. A meta-analysis of two studies showed the desogestrel group had a higher mean fasting glucose (MD 0.20; 95% CI 0.00 to 0.41). Where data could not be combined, single studies showed lower mean fasting glucose (MD -0.40; 95% CI -0.72 to -0.08) and higher means for two-hour glucose response (MD 1.08; 95% CI 0.45 to 1.71) and insulin area under the curve (AUC) (MD 20.30; 95% CI 4.24 to 36.36). Three trials examined the etonogestrel vaginal ring and one examined an etonogestrel implant. One trial showed the ring group had lower mean AUC insulin than the levonorgestrel-COC group (MD -204.51; 95% CI -389.64 to -19.38). Of eight trials of norethisterone preparations, five compared COCs and three compared injectables. In a COC trial, a norethisterone group had smaller mean change in glucose two-hour response than a levonorgestrel-COC group (MD -0.30; 95% CI -0.54 to -0.06). In an injectable study, a group using depot medroxyprogesterone acetate had higher means than the group using norethisterone enanthate for fasting glucose (MD 10.05; 95% CI 3.16 to 16.94), glucose two-hour response (MD 17.00; 95% CI 5.67 to 28.33), and fasting insulin (MD 3.40; 95% CI 2.07 to 4.73). Among five recent trials, two examined newer COCs with different estrogen types. One showed the group with nomegestrel acetate plus 17\u03b2-estradiol had lower means than the levonorgestrel group for incremental AUC glucose (MD -1.43; 95% CI -2.55 to -0.31) and glycosylated hemoglobin (HbA1c) (MD -0.10; 95% CI -0.18 to -0.02). Two trials compared extended versus conventional (cyclic) regimens. With a dienogest COC, an extended-use group had greater mean change in AUC glucose (MD 82.00; 95% CI 10.72 to 153.28). In a small trial using two levonorgestrel COCs, the lower-dose group showed smaller mean change in fasting glucose (MD -3.00; 95% CI -5.89 to -0.11), but the obese and normal weight women did not differ significantly. Current evidence suggests no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes. We cannot make strong statements due to having few studies that compared the same types of contraceptives. Many trials had small numbers of participants and some had large losses. Many of the earlier studies had limited reporting of methods. We still know very little about women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria. Only one small trial stratified the groups by body mass index (obese versus normal).",
        "gold": "In April 2014, we looked for randomized trials of how the body handles carbohydrates when using birth control methods with hormones. Outcomes were blood glucose or insulin levels. Birth control methods could contain estrogen and progestin or just progestin. The type could be pills, shots (injections), implants (matchstick-size rods put under the skin), the vaginal ring, or an intrauterine device (IUD). The studies had to compare two types of birth control or one type versus a placebo or 'dummy' method. We included 31 trials. None had a placebo. Of 34 pairs of birth control methods compared, eight showed some difference by study groups. Twelve trials studied pills with desogestrel. The few differences were not consistent. Three trials looked at the etonogestrel ring. One showed the ring group had lower insulin than the pill group. Eight trials looked at the progestin norethisterone. A group using norethisterone pills had less glucose change than those taking other pills. In another study, a group using the injectable \u2018depo\u2019 (depot medroxyprogesterone acetate) had higher glucose and insulin than the group using another injectable. Of five new trials, two used different estrogen types. In one study, a group taking a pill with ethinyl valerate had lower glucose than a group taking a standard pill. Two other trials compared taking pills for several cycles without stopping (extended use) versus usual use. In one using a dienogest pill, the extended-use group had more glucose change. A small trial used two levonorgestrel pills, and looked at obese and normal weight women. The outcomes did not differ much between those groups. In women without diabetes, hormone contraceptives have little effect on the body's carbohydrate use. Few studies compared the same types of birth control. Therefore, we cannot make strong statements. Many trials had small numbers of women, and many women dropped out. Older trials often did not report all the study methods. Many trials did not include overweight women."
    },
    {
        "index": "cochrane-simplification-test-247",
        "sentence": "We considered that seven of the 10 included RCTs had a low risk of bias. However, the results may be vulnerable to performance and detection bias as none of the RCTs were able to blind participants to treatment allocation and, while most RCTs reported blinded outcome assessment, pain, physical function and quality of life were participant self reported. One of the 10 RCTs was only reported as a conference abstract and did not provide sufficient data for the evaluation of bias risk. High-quality evidence from nine trials (549 participants) indicated that exercise reduced pain (standardised mean difference (SMD) -0.38, 95% confidence interval (CI) -0.55 to -0.20) and improved physical function (SMD -0.38, 95% CI -0.54 to -0.05) immediately after treatment. Pain and physical function were estimated to be 29 points on a 0- to 100-point scale (0 was no pain or loss of physical function) in the control group; exercise reduced pain by an equivalent of 8 points (95% CI 4 to 11 points; number needed to treat for an additional beneficial outcome (NNTB) 6) and improved physical function by an equivalent of 7 points (95% CI 1 to 12 points; NNTB 6). Only three small studies (183 participants) evaluated quality of life, with overall low quality evidence, with no benefit of exercise demonstrated (SMD -0.07, 95% CI -0.23 to 0.36). Quality of life was estimated to be 50 points on a norm-based mean (standard deviation (SD)) score of 50 (10) in the general population in the control group; exercise improved quality of life by 0 points. Moderate-quality evidence from seven trials (715 participants) indicated an increased likelihood of withdrawal from the exercise allocation (event rate 6%) compared with the control group (event rate 3%), but this difference was not significant (risk difference 1%; 95% CI -1% to 4%). Of the five studies reporting adverse events, each study reported only one or two events and all were related to increased pain attributed to the exercise programme. The reduction in pain was sustained at least three to six months after ceasing monitored treatment (five RCTs, 391 participants): pain (SMD -0.38, 95% CI -0.58 to -0.18). Pain was estimated to be 29 points on a 0- to 100-point scale (0 was no pain) in the control group, the improvement in pain translated to a sustained reduction in pain intensity of 8 points (95% CI 4 to 12 points) compared with the control group (0 to 100 scale). The improvement in physical function was also sustained (five RCTs, 367 participants): physical function (SMD -0.37, 95% CI -0.57 to -0.16). Physical function was estimated to be 24 points on a 0- to 100-point scale (0 was no loss of physical function) in the control group, the improvement translated to a mean of 7 points (95% CI 4 to 13) compared with the control group. Only five of the 10 RCTs exclusively recruited people with symptomatic hip OA (419 participants). There was no significant difference in pain or physical function outcomes compared with five studies recruiting participants with hip or knee OA (130 participants). Pooling the results of these 10 RCTs demonstrated that land-based therapeutic exercise programmes can reduce pain and improve physical function among people with symptomatic hip OA.",
        "gold": "This summary of an update of a Cochrane review presents what we know from research about the effect of exercise for people with OA of the hip. After searching for all relevant studies up to February 2013, we included five new studies since the last version of the review, giving 10 studies (549 participants) with mostly mild-to-moderate symptomatic hip OA, alone or with knee OA. Except for one study where participants enrolled in a tai chi programme, all other participants underwent land-based exercise programmes consisting of traditional muscle strengthening, functional training and aerobic fitness programmes, either individually supervised or as part of a group, compared with people who did not exercise. Pain on a scale of 0 to 100 points (lower scores mean reduced pain): - People who completed an exercise programme rated their pain to be 8 points lower (4 to 11 points lower) at end of treatment (8% absolute improvement) compared with people who did not exercise. - People who completed an exercise programme rated their pain as 21 points. - People who did not exercise rated their pain as 29 points. Physical function on a scale of 0 to 100 points (lower score means better physical function): - People who completed an exercise programme rated their physical function to be 7 points lower (1 to 12 points lower) at end of treatment (7% absolute improvement) compared with people who did not exercise. - People who completed an exercise programme rated their physical function as 22 points. - People who did not exercise rated their physical function as 29 points. Quality of life (higher score means better quality of life): - Overall, people with hip OA participating in the studies had a similar quality of life compared with the general population (normative scores of average 50 points), and quality of life was not further improved by participation in an exercise programme: 0 points higher. - People who completed an exercise programme rated their quality of life as 50 points on a population norm-based scale. - People who did not exercise rated their quality of life as 50 points on a population norm-based scale. Withdrawals - three more people out of 100 dropped out of the exercise programme (1% absolute increase). - Six out of 100 people in exercise programmes dropped out. - Three out of 100 people who did not exercise dropped out. This review showed that there is high-quality evidence that in people with hip OA, exercise reduced pain slightly and improved physical function slightly. Further research is unlikely to change the estimate of these results. Low-quality evidence indicated that exercise may not improve quality of life. Further research is likely to change the estimate of these results. Moderate-quality evidence showed that exercise probably does not increase study drop-outs. Further research may change the estimate. We do not have precise information about side effects such as injuries or falls during exercise, but we would expect these to be rare, and no injuries were reported in the studies."
    },
    {
        "index": "cochrane-simplification-test-248",
        "sentence": "Nine high-methodological-quality RCTs(260 participants) met the inclusion criteria. Six trials focussed on comparison of exercise therapy versus no exercise therapy, whereas three trials compared two interventions that both met our definition of exercise therapy. Best evidence synthesis showed strong evidence in favour of exercise therapy compared to no exercise therapy in terms of muscle power function, exercise tolerance functions and mobility-related activities. Moderate evidence was found for improving mood. No evidence was observed for exercise therapy on fatigue and perception of handicap when compared to no exercise therapy. Finally, no evidence was found that specific exercise therapy programmes were more successful in improving activities and participation than other exercise treatments. No evidence of deleterious effects of exercise therapy was described in included studies. The results of the present review suggest that exercise therapy can be beneficial for patients with MS not experiencing an exacerbation. There is an urgent need for consensus on a core set of outcome measures to be used in exercise trials. In addition, these studies should experimentally control for 'dose' of treatment, type of MS and should include sufficient contrast between experimental and control groups.",
        "gold": "To date, there is no effective treatment for MS, however, a number of studies suggest that exercise interventions aimed to improve daily functioning of patients with MS are effective. Nine randomized controlled trials of exercise therapy for MS patients were included in this review six of which used no therapy as the comparator. There was strong evidence in favor of exercise therapy, compared to no therapy, regarding muscle function and mobility while no evidence was found of improved fatigue, in one study only. No one specifically targeted exercise program was more successful than others. No deleterious effects were described in the included studies."
    },
    {
        "index": "cochrane-simplification-test-249",
        "sentence": "Only one trial including 75 participants (average age: 43 years; females: 65% of participants), randomised to early laparoscopic cholecystectomy (less than 24 hours after diagnosis) (n = 35) or delayed laparoscopic cholecystectomy (mean waiting period of 4.2 months) (n = 40), contributed information to this review. The trial had a high risk of bias. Information on the outcome mortality was available for the 75 participants. Information on serious adverse events was available for 68 participants (28 people in the early group and 40 people in the delayed group). The other outcomes were available for 28 participants in the early laparoscopic cholecystectomy group and 35 participants in the delayed laparoscopic cholecystectomy group. There were no deaths in the early group (0/35) (0%) versus 1/40 (2.5%) in the delayed laparoscopic cholecystectomy group (P > 0.9999). There was no bile duct injury in either group. There were no serious adverse events related to the surgery in either group. During the waiting period, complications developed in the delayed laparoscopic cholecystectomy group. The complications that the participants suffered included pancreatitis (n = 1), empyema of the gallbladder (n = 1), gallbladder perforation (n = 1), acute cholecystitis (n = 2), cholangitis (n = 2), obstructive jaundice (n = 2), and recurrent biliary colic (requiring hospital visits) (n = 5). In total, 14 participants required hospital admissions for the above symptoms. All of these admissions occurred in the delayed group as all the participants were operated on within 24 hours in the early group. The proportion of people who developed serious adverse events was 0/28 (0%) in the early group, which was significantly lower than in the delayed laparoscopic cholecystectomy group 9/40 (22.5%) (P = 0.0082). This trial did not report quality of life or return to work. There was no significant difference in the proportion of people who required conversion to open cholecystectomy in the early group 0/28 (0%) compared with the delayed group (6/35 or 17.1%) (P = 0.0743). There was a statistically significant shorter hospital stay in the early group than in the delayed group (MD -1.25 days, 95% CI -2.05 to -0.45). There was a statistically significant shorter operating time in the early group than the delayed group (MD -14.80 minutes, 95% CI -18.02 to -11.58). Based on evidence from only one high-bias risk trial, it appears that early laparoscopic cholecystectomy (less than 24 hours after diagnosis of biliary colic) decreases the morbidity during the waiting period for elective laparoscopic cholecystectomy (mean waiting time 4.2 months), the hospital stay, and operating time. Further randomised clinical trials are necessary to confirm or refute these findings, and to determine if early laparoscopic cholecystectomy is better than the delayed laparoscopic cholecystectomy if the waiting time is shortened further.",
        "gold": "Only one trial including 75 participants (average age: 43 years; females: 65% of participants) provided information for this review. In this trial, 35 participants underwent early laparoscopic cholecystectomy (less than 24 hours after diagnosis) and 40 participants underwent delayed laparoscopic cholecystectomy after an average waiting period of approximately four months. The treatment that the participants underwent was determined by a method similar to the toss of a coin. This trial was at high risk of bias (systematic errors or errors in study design which may influence the conclusions). There were no deaths in the early group (0 out of 35) (0%) and there was one death (1 out of 40) (2.5%) in the delayed laparoscopic cholecystectomy group. This difference between the groups was not significantly different. There were no serious complications related to the surgery in either group. During the waiting period, 9 out of 40 participants (22.5%) developed gallstone-related serious complications. Five participants in the delayed group revisited the hospital because of recurrent gallbladder pain. In total, 14 participants required hospital admissions for the above symptoms. All of these participants were from the delayed group. All the participants in the early group were operated on within 24 hours. The proportion of participants who developed serious complications was significantly lower in the early group than the proportion of participants in the delayed laparoscopic cholecystectomy group. Quality of life and return to work were not reported in this trial. There was no significant difference in the proportion of participants who required conversion to open removal of the gallbladder. The hospital stay was significantly shorter (by about one day) in the early group than the delayed group. The operating time was significantly shorter (by about 15 minutes) in the early group than the delayed group. Based on evidence from only one high-bias risk trial, it appears that early laparoscopic cholecystectomy performed within 24 hours of diagnosis of biliary colic decreases serious complications, hospital stay, and operating time compared with delayed laparoscopic cholecystectomy with an average waiting time of four months. Further well designed, randomised clinical trials are necessary to confirm or refute these findings."
    },
    {
        "index": "cochrane-simplification-test-250",
        "sentence": "A total of 11 trials were included in this review. Most of the studies had an unclear risk of bias prompting us to downgrade the quality of evidence for our outcomes. Seven of these trials provided evidence for the main comparison and the primary outcome and these were pooled. Overall, long-term antibiotic prophylaxis probably reduces the risk of SSI (plausible effects range between a 76% to a 0.26% relative reduction in SSI with long-term antibiotic prophylaxis) (472 participants; RR 0.42, 95% CI 0.24 to 0.74; moderate-quality evidence). There is uncertainty surrounding the relative effects of short-term antibiotics compared with a single dose (220 participants; RR 0.34, 95% CI 0.09 to 1.22; low-quality evidence). No reports described adverse effects associated with the drugs in those trials that reported in this outcome. None of these trials assessed or reported data regarding other outcomes, and information was insufficient to show whether a specific antibiotic is better than another. For people undergoing orthognathic surgery, long term antibiotic prophylaxis decreases the risk of SSI compared with short-term antibiotic prophylaxis and the is uncertainty of whether short-term antibiotic prophylaxis decreases SSi risk relative to a single pre-operative dose of prophylactic antibiotics.",
        "gold": "We conducted a comprehensive search for studies on this topic. We collected data from all studies addressing this question and summarised them to determine whether antibiotics could prevent infection after surgery, whether this treatment has any adverse effects, whether it reduces the number of days that patients need to be in the hospital and whether it improves overall health status. We found 11 studies. Overall, long-term antibiotics reduce the risk of SSI, and there is uncertainty regarding the effects of receiving one dose of antibiotics preoperatively versus short term antibiotics. There was no investigation of side effects of antibiotics in these studies, but in the studies where side effects were investigated, no side effects were found. None of the other effects of interest to clinicians or patients were measured in the studies, and information was insufficient to show whether any single antibiotic is better than any other."
    },
    {
        "index": "cochrane-simplification-test-251",
        "sentence": "We included one study, involving 40 infants and 42 women. The trial was underpowered to detect clinically important outcome differences between the two policies. There were no significant benefits or adverse effects of elective preterm birth at 36 weeks' gestation for fetal gastroschisis. The primary outcomes were caesarean section and neonatal survival to discharge. Two babies died after birth but before discharge in the elective (intervention) group versus none in the spontaneous group (risk ratio (RR) 5.00; 95% confidence interval (CI) 0.26 to 98.00; one study, n = 40). Seven women (33%) in the elective group and nine women (43%) in the spontaneous group delivered by caesarean section (RR 0.78; 95% CI 0.36 to 1.70). Similarly, for the secondary outcomes, there were no statistical differences in birthweight, ventilation requirements, necrotising enterocolitis and requirement for repeat surgery between the two groups. None of our prespecified maternal secondary outcomes were reported in the included study. We also examined gestational age at birth as a non-prespecified outcome. There was a difference in gestational age at birth between the two arms of the trial (35.8 weeks (SD 0.7) in the elective group and 36.7 (SD 1.5) in the spontaneous group. Possible reasons for this small mean difference include a trend towards spontaneous preterm birth in pregnancies complicated by fetal gastroschisis. This review is unable to draw any firm conclusions regarding preterm birth for infants with gastroschisis. It is not possible to say whether the intervention is beneficial or harmful for these babies or their mothers. Only one small trial is included. Further research is needed in this area.",
        "gold": "This review identified one small randomised controlled trials, involving 42 women. There were no significant differences in outcomes for mother or baby when pre-term birth at 36 weeks was planned, compared with later birth. However, it was such a small trial that it does not rule out important benefits or harms from early birth. There was also small overall difference in gestational age at birth between the two groups in the trial, possibly because of the high rate of spontaneous preterm birth with this condition. Further trials are needed."
    },
    {
        "index": "cochrane-simplification-test-252",
        "sentence": "Three studies in adults satisfied the inclusion criteria, lasting up to one week; 122 participants were randomised initially, and 95 completed treatment. We found no studies in children. One study was parallel-group, and two had a cross-over design. All used paracetamol as an add-on to established treatment with strong opioids (median daily morphine equivalent doses of 60 mg, 70 mg, and 225 mg, with some participants taking several hundred mg of oral morphine equivalents daily). Other non-paracetamol medication included non-steroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, or neuroleptics. All studies were at high risk of bias for incomplete outcome data and small size; none was unequivocally at low risk of bias. None of the studies reported any of our primary outcomes: participants with pain reduction of at least 50%, and at least 30%, from baseline; participants with pain no worse than mild at the end of the treatment period; participants with Patient Global Impression of Change (PGIC) of much improved or very much improved (or equivalent wording). What pain reports there were indicated no difference between paracetamol and placebo when added to another treatment. There was no convincing evidence of paracetamol being different from placebo with regards to quality of life, use of rescue medication, or participant satisfaction or preference. Measures of harm (serious adverse events, other adverse events, and withdrawal due to lack of efficacy) were inconsistently reported and provided no clear evidence of difference. Our GRADE assessment of evidence quality was very low for all outcomes, because studies were at high risk of bias from several sources. There is no high-quality evidence to support or refute the use of paracetamol alone or in combination with opioids for the first two steps of the three-step WHO cancer pain ladder. It is not clear whether any additional analgesic benefit of paracetamol could be detected in the available studies, in view of the doses of opioids used.",
        "gold": "In this review we set out to examine all the evidence on how well paracetamol (alone or with morphine-like drugs) worked in adults and children with cancer pain. We also wanted to know how many people had side effects, and how severe those side effects were, for example, whether they caused people to stop taking their medicines. In March 2017, we found three studies with 122 participants. All compared paracetamol plus opioid with the same dose of opioid alone. The studies were small, and were of poor quality. They used different study designs and different ways of showing their pain results. Outcomes of importance to people with cancer pain were not reported. We found no evidence that taking paracetamol alone made any difference to the level of pain experienced. We found no evidence that taking paracetamol together with a morphine-like drug was better than the morphine-like drug alone. Paracetamol did not appear to improve quality of life. No conclusions could be reached about side effects. The amount of information and the differences in how studies were reported meant that no conclusions could be made. The quality of the evidence was very low. Very low-quality evidence means that we are very uncertain about the impact of paracetamol for treating cancer pain. We do not know whether using paracetamol alone, or in combination with an opioid such as codeine or morphine, is worthwhile."
    },
    {
        "index": "cochrane-simplification-test-253",
        "sentence": "Of the 15 trials identified, 14 were conducted in China and 14 in hospitals. The quality of reporting was poor with no studies clearly describing allocation concealment and much data were missing or unusable. All results are vulnerable to considerable bias. Most frequently the primary outcome was the diameter of the wet patch on the pillow. Antimuscarinics (astemizole, diphenhydramine, propantheline, doxepin) were the most commonly evaluated drugs. For the outcome of 'no clinically important improvement' astemizole and diphenhydramine were more effective than placebo (astemizole: n=97, 2 RCTs, RR 0.61 CI 0.47 to 0.81 NNT 3 CI 2 to 5; diphenhydramine: n=131, 2 RCTs, RR 0.43 CI 0.31 to 0.58, NNT 2 CI 1.5 to 2.5), but the doses of astemizole used were those that can cause toxicity. Data involving propantheline were heterogeneous (I2= 86.6%), but both studies showed benefit over placebo. Adverse effects were poorly recorded. Of the other interventions, oryzanol (rice bran oil and rice embryo oil extract) showed benefit over the antimuscarinic doxepin in terms of 'no clinically important change' (n=104, 1 RCT, RR 0.45 CI 0.27 to 0.75, NNT 4 CI 2 to 7). The Chinese medicine suo quo wan (comprises spicebush root, Chinese yam and bitter cardamom) showed benefit over doxepin (n=70, 1 RCT, RR 'no clinically important change' 0.31 CI 0.16 to 0.59, NNT 3 CI 1.5 to 3.7). There are currently insufficient data to confidently inform clinical practice. The limitations of these studies are plentiful and the risk of bias is high. These trials, however, are invaluable guides for current and future study design. Well conducted randomised trials are possible. Some may be underway. Current practice outside of well designed randomised trials should be clearly justified.",
        "gold": "Clozapine is an antipsychotic medication used in the treatment of schizophrenia, a mental health problem that can cause symptoms such as hallucinations and delusions and social withdrawal.\u00a0Clozapine may be useful in those for whom other medications have not worked very well.\u00a0One of the common side-effects of clozapine is having too much saliva in the mouth (hypersalivation).\u00a0This can be embarrassing in public and problematic, especially at night.\u00a0This review is about ways of reducing this problem and includes 15 trials containing 964 people, most of which were done in hospitals in China.\u00a0Treatments included medications that had previously been useful for this problem or were thought to work in theory. The medications used were from a group of drugs called antimuscarinics, traditional Chinese medicines or others. The trials were short (all four weeks or less). From these trials the antimuscarinics; astemizole, diphenhydramine and propantheline, were shown to be better than placebo at reducing hypersalivation. Another medication called oryzanol and a Chinese traditional medicine called Suo quo wan were found to have benefit over doxepin, an antimuscarinic. However, because of the shortness of the trials, poor reporting and the limitations of design, it is difficult to draw any firm conclusions from these results.\u00a0   (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK, www.rethink.org)"
    },
    {
        "index": "cochrane-simplification-test-254",
        "sentence": "We included six RCTs, comprising 195 participants with MS. Two RCTs investigated inspiratory muscle training with a threshold device; three RCTs, expiratory muscle training with a threshold device; and one RCT, regular breathing exercises. Eighteen participants (\u02dc 10%) dropped out; trials reported no serious adverse events. We pooled and analyzed data of 5 trials (N=137) for both inspiratory and expiratory muscle training, using a fixed-effect model for all but one outcome. Compared to no active control, meta-analysis showed that inspiratory muscle training resulted in no significant difference in maximal inspiratory pressure (mean difference (MD) 6.50 cmH2O, 95% confidence interval (CI) \u22127.39 to 20.38, P = 0.36, I2 = 0%) or maximal expiratory pressure (MD \u22128.22 cmH2O, 95% CI \u221226.20 to 9.77, P = 0.37, I2 = 0%), but there was a significant benefit on the predicted maximal inspiratory pressure (MD 20.92 cmH2O, 95% CI 6.03 to 35.81, P = 0.006, I2 = 18%). Meta-analysis with a random-effects model failed to show a significant difference in predicted maximal expiratory pressure (MD 5.86 cmH2O, 95% CI \u221210.63 to 22.35, P = 0.49, I2 = 55%). These studies did not report outcomes for health-related quality of life. Three RCTS compared expiratory muscle training versus no active control or sham training. Under a fixed-effect model, meta-analysis failed to show a significant difference between groups with regard to maximal expiratory pressure (MD 8.33 cmH2O, 95% CI \u22120.93 to 17.59, P = 0.18, I2 = 42%) or maximal inspiratory pressure (MD 3.54 cmH2O, 95% CI \u22125.04 to 12.12, P = 0.42, I2 = 41%). One trial assessed quality of life, finding no differences between groups. For all predetermined secondary outcomes, such as forced expiratory volume, forced vital capacity and peak flow pooling was not possible. However, two trials on inspiratory muscle training assessed fatigue using the Fatigue Severity Scale (range of scores 0-56 ), finding no difference between groups (MD, \u22120.28 points, 95% CI\u22120.95 to 0.39, P = 0.42, I2 = 0%). Due to the low number of studies included, we could not perform cumulative meta-analysis or subgroup analyses. It was not possible to perform a meta-analysis for adverse events, no serious adverse were mentioned in any of the included trials. The quality of evidence was low for all outcomes because of limitations in design and implementation as well as imprecision of results. This review provides low-quality evidence that resistive inspiratory muscle training with a resistive threshold device is moderately effective postintervention for improving predicted maximal inspiratory pressure in people with mild to moderate MS, whereas expiratory muscle training showed no significant effects. The sustainability of the favourable effect of inspiratory muscle training is unclear, as is the impact of the observed effects on quality of life.",
        "gold": "We searched electronic databases for randomized controlled trials (where participants are assigned at random to either a treatment or a control arm) published up to 3 February 2017 that investigated respiratory muscle training in people with MS. In addition, we contacted experts in the field to identify additional studies. We found six trials involving 195 participants with MS. Training consisted of two or three sets of 10 to 15 repetitions, twice a day for at least three days a week, and interventions lasted for six weeks to three months. Follow-up ranged from no follow-up to six months. Two of the included trials investigated inspiratory muscle training with a threshold device (i.e. a portable breathing device that increases airflow resistance while inhaling or exhaling). Three trials investigated expiratory muscle training with a threshold device, and one trial investigated breathing exercises. We found benefits with inspiratory muscle training for improving predicted maximal inspiratory pressure, but not for improving measured maximal inspiratory pressure. We did not find any effects for maximal expiratory pressure. Only one study measured quality of life, but it did not find any effects; two trials measured fatigue and also failed to find a difference between the treatment and control groups. Eighteen participants (\u02dc 10%) dropped out, and no trials reported any serious adverse events. The six trials that were eligible for inclusion in this review were small, so statistical power was low, making analyses less precise. In addition, studies were heterogeneous in terms of the type of respiratory muscle training, dosing/intensity, and the severity of MS. In addition, we could not analyze the effects of training on, for example, cough efficacy, pneumonia, and quality of life, as the included trials did not report on these outcomes even though they are important for patients, caregivers and healthcare professionals. Altogether, this review provides low-quality evidence that resistive inspiratory muscle training improves predicted inspiratory muscle strength in people with MS. We did not find any effects for resistive expiratory muscle training. More high-quality research in respiratory muscle training in MS is needed."
    },
    {
        "index": "cochrane-simplification-test-255",
        "sentence": "This review included one RCT in which 38 women (41 pregnancies) were randomised, with only 26 women (28 pregnancies) being analysed. This RCT comparing the effect of betamethasone (1.5 mg/day) with no medication found no statistically significant difference in neonatal thrombocytopenia (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.62 to 2.05) and neonatal bleeding (RR 1.00, 95% CI 0.24 to 4.13). Review authors conducted an intention-to-treat analysis which showed similar findings: RR 1.18, 95% CI 0.57 to 2.45 and RR 1.05, 95% CI 0.24 to 4.61, respectively. Maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage were not studied by this RCT. Current evidence indicates that compared to no medication, betamethasone did not reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during pregnancy. There is insufficient evidence to support the use of betamethasone for treating ITP. This Cohrane review does not provide evidence about other medical treatments for ITP during pregnancy. This systematic review also identifies the need for well-designed, adequately powered randomised clinical trials for this medical condition during pregnancy. Unless randomised clinical trials provide evidence of a treatment effect and the trade off between potential benefits and harms are established, policy-makers, clinicians, and academics should not use betamethasone for ITP in pregnant women. Any future trials on medical treatments for treating ITP during pregnancy should test a variety of important maternal, neonatal or both outcome measures, including maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage.",
        "gold": "Current evidence from one randomised controlled trial indicates that betamethasone does not reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during pregnancy when compared to no medication. We could not identify evidence on other medical treatments for ITP during pregnancy. This review included one controlled trial in which 38 women (41 pregnancies) were randomised, with only 26 women (28 pregnancies) being analysed. There was also a severe imbalance between comparison groups. Giving the mother betamethasone (1.5 mg/day) did not result in a difference in the neonatal platelet count at birth and at the first week of life. The study reported that the maternal platelet count of peripheral blood did not change significantly during the study period for both the betamethasone and no treatment groups. Maternal postpartum haemorrhage and neonatal intracranial haemorrhage were not studied. Nor were maternal clinical and pregnancy outcomes reported. The researchers used no treatment in the control group, which may have increased the risk of performance bias in the trial."
    },
    {
        "index": "cochrane-simplification-test-256",
        "sentence": "We identified two completed studies, with a total of 111 participants (n = 30 and n = 81), both conducted in Iran, that met our inclusion criteria. Participants had moderate to severe keratoconus pre-operatively and were randomly allocated to receive either DALK or penetrating keratoplasty. Only one eye of each participant was treated as part of the trials. The smaller study had 12 month follow-up data for all participants. For the larger study, four DALK surgeries had to be abandoned due to technical failure and visual and refractive outcomes were not measured in these participants. Follow-up length for the remaining 77 participants ranged from 6.8 to 36.4 months, with all 77 followed for at least three months post-suture removal. Details of the randomisation procedure were unavailable for the smaller study and so sensitivity analyses were conducted to determine if the results from this study had affected the overall results of the review. Neither of the included studies reported a difference between groups on any of the measures of post-graft visual achievement, keratometric astigmatism or spherical equivalent. A single case of graft failure in a penetrating keratoplasty was reported. No postoperative graft failures were reported in the DALK group of either study. Instances of graft rejection were reported in both groups, in both studies. The majority of these cases were successfully treated with steroids. The data, which related to all cases in each study - given that the four cases that did not go ahead as planned had already technically failed without presence of rejection - showed that rejection was less likely to occur in DALK (odds ratio (OR): 0.33, 95% confidence interval (CI) 0.14 to 0.81, GRADE rating: moderate). Results of the sensitivity analysis indicated that inclusion of the Razmju 2011 study did not bias the results with regards to rejection episodes. While sensitivity analysis showed altered results with regards to failure rates, the data available from the Javadi 2010 study alone had a very wide 95% CI, suggesting an imprecise estimate. Therefore, even after removal of the Razmju 2011 data, it is still difficult to draw conclusions regarding superiority of one technique over another with regards to graft failure. DALK was unable to be completed as planned in four cases and in a further three cases, complications during dissection required further intervention. Other adverse events, of varying severity, were reported in both intervention groups with similar frequency. For both types of surgery, these included postoperative astigmatism, steroid induced ocular hypertension and persistent epithelial defects. In recipients of DALK, one participant had interface neovascularisation (a proliferation of blood vessels where the host and donor cornea come together) and one had wrinkling of Descemet's membrane, the basement membrane separating the corneal stroma from the corneal endothelium. In the penetrating keratoplasty groups, one participant required graft resuturing and one had an atonic pupil, a condition in which the pupil dilates and is non-reactive. Overall, the quality of the evidence was rated as very low to moderate, with methodological limitations, incomplete data analysis and imprecision of findings, as well as high risk of bias in several areas for both studies. We found no evidence to support a difference in outcomes with regards to BCVA at three months post-graft or at any of the other time points analysed (GRADE rating: very low). We also found no evidence of a difference in outcomes with regards to graft survival, final UCVA or keratometric outcomes. We found some evidence that rejection is more likely to occur following penetrating keratoplasty than DALK (GRADE rating: moderate). The small number of studies included in the review and methodological issues relating to the two, mean that the overall quality of the evidence in this review is low. There is currently insufficient evidence to determine which technique may offer better overall outcomes - final visual acuity and time to attain this, keratometric stabilisation, risk of rejection or failure, or both, and risk of other adverse events - for patients with keratoconus. Large randomised trials comparing the outcomes of penetrating keratoplasty and DALK in the treatment of keratoconus are needed.",
        "gold": "We included two randomised controlled trials (RCTs) which involved a total of 111 participants in this review. Both trials were conducted in single medical centres in Iran and compared the outcomes, at least three months post-suture removal (for a minimum of 12 months in the newer study, and for a range of 6.8 to 36.4 months in the older study), of participants with keratoconus who had received DALK to those who had received penetrating keratoplasty. The evidence is current to October 2013. The results suggested that graft rejection is more likely to occur following penetrating keratoplasty, however likelihood of graft failure was similar in both groups, as were visual and structural results. DALK was unable to be completed as planned in four cases and in a further three cases complications during dissection required further intervention. Other adverse events, of varying severity, were reported in both intervention groups. For both types of surgery, these included postoperative astigmatism (when the cornea is no longer perfectly curved), raised pressure in the eye following steroid use, and a failure of the epithelium, the front layer of the eye, to heal properly. In recipients of DALK, one participant had interface neovascularisation (a growth of blood vessels where the host and donor cornea come together) and one had wrinkling of Descemet's membrane, a structural element of the cornea. In the penetrating keratoplasty groups, one participant required graft resuturing and one had an atonic pupil, a condition in which the pupil dilates and is non-reactive. The included studies reported adverse events thoroughly. The evidence remains weak, as the quality of evidence is rated very low to moderate. Large trials comparing the outcomes of DALK and penetrating keratoplasty for the treatment of keratoconus, are needed. These should be randomised single-masked trials, in which graft recipients are unaware of their group allocation. Because of the nature of the surgery, it is not likely to be possible to conduct double-masked trials as practitioners who are qualified to undertake outcomes assessments would be able to see which graft a participant had received. Future trials should include regular, long-term follow-up and consistent methods must be used."
    },
    {
        "index": "cochrane-simplification-test-257",
        "sentence": "The search strategy identified 31,767 records; after screening, 90 full-text reports were assessed for eligibility. We included 67 trials (from 76 reports), recruiting 8506 women; the number of women included in analyses varied greatly between outcomes, with endpoint haemoglobin concentration being the outcome with the largest number of participants analysed (6861 women). Only 10 studies were considered at low overall risk of bias, with most studies presenting insufficient details about trial quality. Women receiving iron were significantly less likely to be anaemic at the end of intervention compared to women receiving control (risk ratio (RR) 0.39 (95% confidence interval (CI) 0.25 to 0.60, 10 studies, 3273 women, moderate quality evidence). Women receiving iron had a higher haemoglobin concentration at the end of intervention compared to women receiving control (mean difference (MD) 5.30, 95% CI 4.14 to 6.45, 51 studies, 6861 women, high quality evidence). Women receiving iron had a reduced risk of iron deficiency compared to women receiving control (RR 0.62, 95% CI 0.50 to 0.76, 7 studies, 1088 women, moderate quality evidence). Only one study (55 women) specifically reported iron-deficiency anaemia and no studies reported mortality. Seven trials recruiting 901 women reported on 'any side effect' and did not identify an overall increased prevalence of side effects from iron supplements (RR 2.14, 95% CI 0.94 to 4.86, low quality evidence). Five studies recruiting 521 women identified an increased prevalence of gastrointestinal side effects in women taking iron (RR 1.99, 95% CI 1.26 to 3.12, low quality evidence). Six studies recruiting 604 women identified an increased prevalence of loose stools/diarrhoea (RR 2.13, 95% CI 1.10, 4.11, high quality evidence); eight studies recruiting 1036 women identified an increased prevalence of hard stools/constipation (RR 2.07, 95% CI 1.35 to 3.17, high quality evidence). Seven studies recruiting 1190 women identified evidence of an increased prevalence of abdominal pain among women randomised to iron (RR 1.55, 95% CI 0.99 to 2.41, low quality evidence). Eight studies recruiting 1214 women did not find any evidence of an increased prevalence of nausea among women randomised to iron (RR 1.19, 95% CI 0.78 to 1.82). Evidence that iron supplementation improves cognitive performance in women is uncertain, as studies could not be meta-analysed and individual studies reported conflicting results. Iron supplementation improved maximal and submaximal exercise performance, and appears to reduce symptomatic fatigue. Although adherence could not be formally meta-analysed due to differences in reporting, there was no evident difference in adherence between women randomised to iron and control. Daily iron supplementation effectively reduces the prevalence of anaemia and iron deficiency, raises haemoglobin and iron stores, improves exercise performance and reduces symptomatic fatigue. These benefits come at the expense of increased gastrointestinal symptomatic side effects.",
        "gold": "We included studies comparing the effects of iron compared with no iron when given at least five days per week to menstruating women. We identified 67 trials recruiting 8506 women eligible for inclusion in the review. Most trials lasted between one and three months. The most commonly used iron form was ferrous sulphate. We found evidence that iron supplements reduce the prevalence of anaemia and iron deficiency, and raise levels of haemoglobin in the blood and in iron stores. Iron supplementation clearly increases the risk of side effects, for example, constipation and abdominal pain. We found high quality evidence that iron improves haemoglobin and produces changes in bowel function, but moderate quality evidence that iron reduces the prevalence of anaemia and iron deficiency. Evidence of the effects of iron on other outcomes, such as abdominal pain, is of low quality. There are no data on the effects of iron on mortality in this population group. Further definitive studies are needed to identify whether taking iron supplements orally for at least five days a week has an impact on key, health-related outcomes."
    },
    {
        "index": "cochrane-simplification-test-258",
        "sentence": "Five studies were included in this review with a total of 1,726 patients. The top-up search resulted in an additional ongoing trial, the results of which have not been incorporated in this review. Among five included studies, no reduction in all-cause mortality was observed in the combination arm, with a summary hazard ratio (HR) of 0.91 (95% CI: 0.81-1.02). Longer progression-free survival was observed in those treated with the combination chemotherapy (HR: 0.68, 95% CI: 0.53-0.87), however, this result may have been driven by findings from the single first-line treatment setting study. The quality of evidence for overall survival was low and for progression-free survival was moderate, mainly due to study limitation from the lack of information on randomisation methods and allocation concealment. There were higher risks of toxicity outcomes grade 3 or 4 diarrhoea and grade 1 or 2 alopecia, and a lower risk of grade 3 or 4 neutropenia in controls compared to the invervention group. Evidence for toxicity has been assessed to be low to moderate quality. There was no overall survival benefit of the irinotecan and fluoropyrimidine treatment over irinotecan alone, thus both regimens remain reasonable options in treating patients with advanced or metastatic CRC. Given the low and moderate quality of the evidence, future studies with sufficient numbers of patients in each treatment arms are needed to clarify the benefit observed in progression-free survival with combination irinotecan and fluoropyrimidines.",
        "gold": "We searched the literature on January 13, 2016. We identified five randomised controlled trials with a total of 1,726 patients comparing the combination of IRI and fluoropyrimidine with IRI alone. The search in January 2016 resulted in an additional ongoing trial, the results of which have not been incorporated in this review. This review compared IRI and fluoropyrimidine with IRI alone in terms of overall survival, progression-free survival, toxicity, response rates and quality of life. There is no evidence to suggest any superiority of the combination of IRI and fluoropyrimidine over IRI alone, but our results on overall survival are limited by the number of studies available to date. Longer progression-free survival was seen from adding fluoropyrimidines to IRI. Based on current evidence, both the combination regimens and IRI alone seem equally effective for treating advanced or metastatic patients. Patients in the intervention arm were less likely to develop grade 3 or 4 diarrhea and grade 1 or 2 alopecia, and more likely to have grade 3 or 4 neutropenia, compared to patients receiving IRI alone. There was moderate quality evidence from these studies suggesting longer progression-free survival from adding fluoropyrimidines to IRI. However, findings need to be confirmed by larger, high-quality randomised clinical trials."
    },
    {
        "index": "cochrane-simplification-test-259",
        "sentence": "Due to the differences in the method of assessment, the variability of data and the heterogeneity of the participant groups it was difficult to pool some of the outcome data. Despite these limitations and potentially significant biases related to methodological quality there was evidence to suggest that a transverse or oblique incision has less impact on pulmonary function particularly in the early post-operative period and is less prone to rupture (wound dehiscence/incisional hernia). The data on pain is less clear and should be interpreted with caution but some data suggests a transverse incision is less painful. There was no difference seen in other early or late post-operative complications and recovery times were similar although the transverse incision may be cosmetically more acceptable. The analgesia use and the pulmonary compromise may be reduced with a transverse/oblique incision but this does not seem to be significant clinically as pulmonary complication rates and recovery times were the same. The likelihood of wound dehiscence and rupture appears to be reduced with a transverse incision and a transverse incision may look better. The methodological and clinical diversity and the potential for bias also mean that the results in favour of a transverse/oblique incision (particularly with regard to analgesic use) should be treated with caution. The optimal incision for abdominal surgery still remains the preference of the surgeon.",
        "gold": "The choice of abdominal surgical incision is determined largely by access. However, a transverse incision may be superior to a midline incision in terms of recovery and complications. All randomised controlled trials comparing these incisions were identified. Outcomes included analgesic use, pulmonary function, complication rates and hospital stay. Marked variability in methodology made comparison difficult and potential biases in all of the studies suggests results should be treated with caution. Nevertheless a trend was seen toward less analgesic requirement, less effect on pulmonary function and lower wound dehiscence and incisional hernia rates with a transverse incision. However, the lower pain and reduced effect on pulmonary function were not translated into other clinical advantages as recovery times and other complication rates (except cosmetic appearance) were similar."
    },
    {
        "index": "cochrane-simplification-test-260",
        "sentence": "We included a total of nine RCTs (981 participants) in this review. Five studies were conducted in Europe and four in North America. Sample sizes ranged from 33 to 351. The mean age across trials ranged between 32.0 and 43.7 years. All included studies were judged as having high risk of performance bias and high risk of detection bias due to lack of blinding, and four of the nine studies suffered from at least one additional source of possible bias. In MBR compared to usual care for subacute LBP, individuals receiving MBR had less pain (four studies with 336 participants; SMD -0.46, 95% CI -0.70 to -0.21, moderate-quality of evidence due to risk of bias) and less disability (three studies with 240 participants; SMD -0.44, 95% CI -0.87 to -0.01, low-quality of evidence due to risk of bias and inconsistency), as well as increased likelihood of return-to-work (three studies with 170 participants; OR 3.19, 95% CI 1.46 to 6.98, very low-quality of evidence due to serious risk of bias and imprecision) and fewer sick leave days (two studies with 210 participants; SMD -0.38 95% CI -0.66 to -0.10, low-quality of evidence due to risk of bias and imprecision) at 12-month follow-up. The effect sizes for pain and disability were low in terms of clinical meaningfulness, whereas effects for work-related outcomes were in the moderate range. However, when comparing MBR to other treatments (i.e. brief intervention with features from a light mobilization program and a graded activity program, functional restoration, brief clinical intervention including education and advice on exercise, and psychological counselling), we found no differences between the groups in terms of pain (two studies with 336 participants; SMD -0.14, 95% CI -0.36 to 0.07, low-quality evidence due to imprecision and risk of bias), functional disability (two studies with 345 participants; SMD -0.03, 95% CI -0.24 to 0.18, low-quality evidence due to imprecision and risk of bias), and time away from work (two studies with 158 participants; SMD -0.25 95% CI -0.98 to 0.47, very low-quality evidence due to serious imprecision, inconsistency and risk of bias). Return-to-work was not reported in any of the studies. Although we looked for adverse events in both comparisons, none of the included studies reported this outcome. On average, people with subacute LBP who receive MBR will do better than if they receive usual care, but it is not clear whether they do better than people who receive some other type of treatment. However, the available research provides mainly low to very low-quality evidence, thus additional high-quality trials are needed before we can describe the value of MBP for clinical practice.",
        "gold": "The search is current to July of 2016. Five studies were conducted in Europe and four in North America. Sample sizes ranged from 33 to 351. The mean age across trials ranged between 32.0 and 43.7 years. The majority of studies included mixed samples of male and female participants. The authors had no concerns about funding sources of any included studies. Overall, we found that multidisciplinary treatments may be better than usual care for people with LBP for a duration of six to 12 weeks. Individuals receiving multidisciplinary treatment had less pain, less disability, increased likelihood of return-to-work and fewer sick leave days at 12-month follow-up. However, when comparing multidisciplinary treatments to other treatments (e.g. brief clinical intervention including education and advice on exercise), we found that multidisciplinary treatments may be no better than other treatments. Although we examined adverse events as a secondary outcome, none of the included studies reported this outcome. The quality of the evidence for this review was generally low to very low. This was mainly due to small sample sizes and other study limitations. Moreover, we grouped together studies with differing interventions and comparisons. For example, some of the multidisciplinary interventions were quite intense (e.g. > 30 hours of treatment), whereas others were designed to be brief (e.g. < three hours). This variability across studies makes it more challenging to interpret the findings. In sum, there is a need for additional, large, high-quality randomised controlled trials before we can make definitive recommendations for clinical practice."
    },
    {
        "index": "cochrane-simplification-test-261",
        "sentence": "We included 18 trials reporting on 4843 participants comparing the effect of bisphosphonate administration to control regimens. Primary outcome: there was no clear difference in the proportion of participants with pain response (RR 1.15, 95% CI 0.93 to 1.43; P = 0.20; I2 = 0%; 3 trials; 876 participants; low quality evidence). In absolute terms, bisphosphonates resulted in a pain response in 40 more participants per 1000 (19 fewer to 114 more). Secondary outcomes: bisphosphonates probably reduced the incidence of skeletal-related events in participants with prostate cancer metastatic to bone (RR 0.87, 95% CI 0.81 to 0.94; P = 0.27; I2 = 19%; 9 trials; 3153 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 58 fewer SREs per 1000 (85 fewer to 27 fewer). We found no clinically relevant differences in mortality (RR 0.97, 95% CI 0.91 to 1.04; P = 0.43; I2 = 1%; 9 trials; 2450 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 16 fewer deaths per 1000 (47 fewer to 21 more). Outcome definition of quality of life and the measurement tools varied greatly across trials and we were unable to extract any quantitative data for meta-analysis. Bisphosphonates probably increased the number of participants affected by nausea (RR 1.19, 95% CI 1.00 to 1.41; P = 0.05; I2 = 0%; 9 trials; 3008 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in seven more cases of nausea per 1000 (0 fewer to 14 more). Bisphosphonates probably increased the number of renal adverse events (RR 1.65, 95% CI 1.11 to 2.46; P = 0.01; I2 = 0%; 7 trials; 1794 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 22 more renal adverse events per 1000 (4 more to 50 more). We found no clear difference in the number of participants with osteonecrosis of the jaw between groups (RR 1.92, 95% CI 0.75 to 4.90; P = 0.17; I2 = 0%; 5 trials; 1626 participants; very low quality evidence). In absolute terms, bisphosphonates resulted in seven more cases with osteonecrosis of the jaw per 1000 (2 fewer to 29 more). We observed no clinically relevant difference in the proportion of participants with decreased analgesic consumption (RR 1.19, 95% CI 0.87 to 1.63; P = 0.28; I2 = 37%; 4 trials; 416 participants). Statistical analysis revealed that bisphosphonates probably reduced the number of participants with disease progression (RR 0.94, 95% CI 0.90 to 0.98; P = 0.006; I2 = 0%; 7 trials; 2115 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 36 fewer cases of disease progression per 1000 (71 fewer to 7 fewer). Findings of our predefined subgroup and sensitivity analyses were no different from those of the primary analyses. Based on low quality evidence, there may be no clinically relevant difference in the proportion of men with pain response between bisphosphonates and control regimens in men with bone metastases from prostate cancer. Bisphosphonates probably decrease the number of skeletal-related events and disease progression. These benefits need to be weighed against the increased risk of renal impairment and nausea in men receiving bisphosphonates. Future studies should explicitly evaluate patient important outcomes such as quality of life and pain by using standardized and comparable assessment tools.",
        "gold": "We searched medical databases to 13 July 2017. Two review authors independently screened, summarized and analyzed the findings. This led to the inclusion of 18 clinical trials. We found low quality evidence that bisphosphonates provided no clinically relevant difference in pain response (three studies involving 876 men) compared to placebo (pretend treatment) or no additional treatment. Bisphosphonates reduced pain in 40 more men per 1000 men (19 fewer to 114 more). We found moderate quality evidence that bisphosphonates probably resulted in 58 fewer skeletal-related events per 1000 (85 fewer to 27 fewer). Bisphosphonates showed no clear difference in the number of men who died or the number of men with decreased use of pain killers. We observed moderate quality evidence that bisphosphonates probably increased the number of men with nausea. Bisphosphonates resulted in seven more men with nausea per 1000 men (0 fewer to 14 more). We found moderate quality evidence that bisphosphonates probably increased the number of men with kidney problems. In this case, bisphosphonates resulted in 22 more men with renal complications per 1000 men (4 more to 50 more). For osteonecrosis of the jaw (where the jaw bone weakens and dies), we found very low quality evidence that bisphosphonates showed no clear difference. We observed moderate quality evidence that bisphosphonates probably decreased the number of men affected by disease progression (where the disease got worse). This means that bisphosphonates resulted in 36 fewer men with disease progression per 1000 men (71 fewer to 7 fewer). We found no useable data on quality of life. We judged the quality of evidence as moderate to very low."
    },
    {
        "index": "cochrane-simplification-test-262",
        "sentence": "Our search strategies led to 3046 potentially relevant references. Of these, five RCTs involving 1093 patients were included; four trials in previously untreated patients and one trial in relapsed patients. Overall, the quality of the five trials is judged to be moderate. All trials were reported as randomised and judged to be open-label studies, because usually trials evaluating stem cell transplantation are not blinded. Due to the small number of studies in each analysis (four or less), the quantification of heterogeneity was not reliable and not evaluated in further detail. A potential source of bias are uncertainties in the HR calculation. For OS, the HR had to be calculated for three trials from survival curves, for PFS for two trials. We found a statistically significant increased PFS in previously untreated FL patients in the HDT + ASCT arm (HR = 0.42 (95% confidence interval (CI) 0.33 to 0.54; P < 0.00001). However, this effect is not transferred into a statistically significant OS advantage (HR = 0.97; 95% 0.76 to 1.24; P = 0.81). The subgroup of trials adding rituximab to both intervention arms (one trial) confirms these results and the trial had to be stopped early after an interim analysis due to a statistically significant PFS advantage in the HDT + ASCT arm (PFS: HR = 0.36; 95% CI 0.23 to 0.55; OS: HR = 0.88; 95% CI 0.40 to 1.92). In the four trials in previously untreated patients there are no statistically significant differences between HDT + ASCT and the control-arm in terms of TRM (RR = 1.28; 95% CI 0.25 to 6.61; P = 0.77), secondary acute myeloid leukaemia/myelodysplastic syndromes (RR = 2.87; 95% CI 0.7 to 11.75; P = 0.14) or solid cancers (RR = 1.20; 95% CI 0.25 to 5.77; P = 0.82). Adverse events were rarely reported and were observed more frequently in patients undergoing HDT + ASCT (mostly infections and haematological toxicity). For patients with relapsed FL, there is some evidence (one trial, N = 70) that HDT + ASCT is advantageous in terms of PFS and OS (PFS: HR = 0.30; 95% CI 0.15 to 0.61; OS: HR = 0.40; 95% CI 0.18 to 0.89). For this trial, no results were reported for TRM, adverse events or secondary cancers. In summary, the currently available evidence suggests a strong PFS benefit for HDT + ASCT compared with chemotherapy or immuno-chemotherapy in previously untreated patients with FL. No statistically significant differences in terms of OS, TRM and secondary cancers were detected. These effects are confirmed in a subgroup analysis (one trial) adding rituximab to both treatment arms. Further trials evaluating this approach are needed to determine this effect more precisely in the era of rituximab. Moreover, longer follow-up data are necessary to find out whether the PFS advantage will translate into an OS advantage in previously untreated patients with FL. There is evidence that HDT + ASCT is advantageous in patients with relapsed FL.",
        "gold": "With this assumption, we assessed the role of high-dose therapy followed by autologous stem cell transplantation in the treatment of follicular lymphoma in adults. We included five trials with 1093 patients in the main analyses. As a result, the meta-analyses for previously untreated patients (four trials) show no statistical significant differences in terms of survival, treatment-related mortality or secondary malignancies between the patients treated with high-dose therapy followed by autologous stem cell transplantation and those treated with chemotherapy only. However, progression-free survival (tumour control), was significantly improved by the high-dose chemotherapy and stem cell transplantation. Adverse events are more common in patients treated with high-dose therapy followed by autologous stem cell transplantation. There is an advantage of the high-dose chemotherapy and stem cell transplantation for patients with a relapse of the disease, both in survival and in tumour control (one trial). No data on adverse events are reported in this trial."
    },
    {
        "index": "cochrane-simplification-test-263",
        "sentence": "We included 15 randomised trials (1437 participants) of WDD for schizophrenia. There was a high risk of performance bias within the trials but overall, risk for selection, attrition and reporting bias was low or unclear. Data showed WDD improved the short-term global state of participants compared with placebo or no treatment (1 RCT n = 72, RR 0.53, 95% CI 0.39 to 0.73, low-quality evidence). When WDD was compared with antipsychotic drugs, such as chlorpromazine or risperidone, no difference in short-term global state of participants was observed (2 RCTs n = 140, RR 1.18 95% CI 0.98 to 1.43, moderate-quality evidence) and mental state (total endpoint Positive and Negative Syndrome Scale (PANSS): 2 RCTs, n = 140, MD 0.84, 95% CI -4.17 to 5.84, low-quality evidence). However, WDD was associated with fewer people experiencing extrapyramidal effects (EPS) compared with other treatments (2 RCTs 0/70 versus 47/70, n = 140, RR 0.02, 95% CI 0.00 to 0.15, moderate-quality evidence). WDD is often used as an add-on intervention alongside antipsychotics. When WDD + antipsychotic was compared to antipsychotic alone, the combination group had better global state (short-term results, 6 RCTs, n = 684, RR 0.60, 95% CI 0.50 to 0.72, moderate-quality evidence) and mental state (short-term total endpoint PANSS: 5 RCTs, n = 580, MD -11.64, 95% CI -13.33 to - 9.94, low-quality evidence), fewer people with EPS (2 RCTs n = 308, RR 0.46, 95% CI 0.30 to 0.70, moderate-quality evidence) and reduction of the mean use of risperidone (1 RCT n = 107, MD -0.70, 95% CI -0.87 to -0.53, low-quality evidence). But, there was no effect on weight gain (1 RCT n = 108, RR 0.50, 95% CI 0.20 to 1.24, low-quality evidence). When WDD + low-dose antipsychotic was compared with normal-dose antipsychotic alone, the combination again showed benefits for short-term global state (7 RCTs n = 522, RR 0.69, 95% CI 0.51 to 0.93, moderate-quality evidence), mental state (total endpoint PANSS: 4 RCTs n = 250, MD -9.53, 95% CI -17.82 to -1.24, low-quality evidence), and fewer participants with EPS (3 RCTS n = 280, RR 0.29, 95% CI 0.16 to 0.51, moderate-quality evidence). Across all comparisons, we found no data on outcomes directly reporting quality of life, hospital service use and economics. Limited evidence suggests that WDD may have some positive short-term antipsychotic global effects compared to placebo or no treatment. However when WDD was compared with other antipsychotics there was no effect on global or mental state, but WDD was associated with fewer adverse effects. When WDD was combined with an antipsychotic, positive effects were found for global and mental state and the combination caused fewer adverse effects. The available evidence is not high quality. Better designed large studies are needed to fully and fairly test the effects of WDD for people with schizophrenia.",
        "gold": "In Feburary 2016, the Information Specialist of the Cochrane Schizophrenia Group ran an electronic search for trials that randomised people with schizophrenia to receive either WDD, placebo/no treatment or antipsychotic drugs. We screened all records found in this search and included those that met our inclusion criteria and reported useful data. Fifteen trials (with a total of 1437 participants) provided useable, but limited, data. Results showed that WDD may have some beneficial effects on short-term global outcomes and mental state of people with schizophrenia compared to placebo or no treatment but did not show a benefit when compared to antipsychotics - although WDD did cause fewer adverse effects. When WDD was combined with an antipsychotic, there were observed benefits for WDD on improving global state and reducing the side effects caused by antipsychotics. Results of this review suggest WDD may be helpful for people with schizophrenia, but these results are based on low to moderate evidence and there is not enough high-quality evidence to make firm conclusions. Better-designed large studies are needed to fully and fairly test the effects of WDD for people with schizophrenia."
    },
    {
        "index": "cochrane-simplification-test-264",
        "sentence": "For this update, we found three new RCTs (228 participants), bringing the total to 12 RCTs with 799 participants. We judged three studies to be at high risk of bias, and three to be at low risk of bias; six were unclear. None of the studies reported the adverse outcome of root resorption. The review assessed six comparisons. 1. Multistrand stainless steel versus superelastic nickel-titanium (NiTi) arch wires. There were five studies in this group and it was appropriate to undertake a meta-analysis of two of them. There is insufficient evidence from these studies to determine whether there is a difference in rate of alignment between multistrand stainless steel and superelastic NiTi arch wires (mean difference (MD) -7.5 mm per month, 95% confidence interval (CI) -26.27 to 11.27; 1 study, 48 participants; low-quality evidence). The findings for pain at day 1 as measured on a 100 mm visual analogue scale suggested that there was no meaningful difference between the interventions (MD -2.68 mm, 95% CI -6.75 to 1.38; 2 studies, 127 participants; moderate-quality evidence). 2. Multistrand stainless steel versus thermoelastic NiTi arch wires. There were two studies in this group, but it was not appropriate to undertake a meta-analysis of the data. There is insufficient evidence from the studies to determine whether there is a difference in rate of alignment between multistrand stainless steel and thermoelastic NiTi arch wires (low-quality evidence). Pain was not measured. 3. Conventional NiTi versus superelastic NiTi arch wires. There were three studies in this group, but it was not appropriate to undertake a meta-analysis of the data. There is insufficient evidence from these studies to determine whether there is any difference between conventional and superelastic NiTi arch wires with regard to either alignment or pain (low- to very low-quality evidence). 4. Conventional NiTi versus thermoelastic NiTi arch wires. There were two studies in this group, but it was not appropriate to undertake a meta-analysis of the data. There is insufficient evidence from these studies to determine whether there is a difference in alignment between conventional and thermoelastic NiTi arch wires (low-quality evidence). Pain was not measured. 5. Single-strand superelastic NiTi versus coaxial superelastic NiTi arch wires. There was only one study (24 participants) in this group. There is moderate-quality evidence that coaxial superelastic NiTi can produce greater tooth movement over 12 weeks (MD -6.76 mm, 95% CI -7.98 to -5.55). Pain was not measured. 6. Superelastic NiTi versus thermoelastic NiTi arch wires. There were three studies in this group, but it was not appropriate to undertake a meta-analysis of the data. There is insufficient evidence from these studies to determine whether there is a difference in alignment or pain between superelastic and thermoelastic NiTi arch wires (low-quality evidence). Moderate-quality evidence shows that arch wires of coaxial superelastic nickel-titanium (NiTi) can produce greater tooth movement over 12 weeks than arch wires made of single-strand superelastic NiTi. Moderate-quality evidence also suggests there may be no difference in pain at day 1 between multistrand stainless steel arch wires and superelastic NiTi arch wires. Other than these findings, there is insufficient evidence to determine whether any particular arch wire material is superior to any other in terms of alignment rate, time to alignment, pain and root resorption.",
        "gold": "We searched for studies on 5 October 2017. We were interested in 'randomised controlled trials' (RCTs), which are studies in which participants are assigned randomly to the interventions being compared. We found 12 RCTs with 799 participants, all of whom had upper or lower full arch fixed braces, or both. The studies evaluated different initial arch wires, but they were poorly conducted or reported, or both, and their results are likely to be biased. The studies varied in a number of other aspects of orthodontic treatment, compared different types of initial arch wires and reported different outcomes at different times. None of the studies reported both potential benefits (straightening) and harms (pain or side effects such as tooth root shortening). We found moderate-quality evidence that coaxial superelastic nickel-titanium (NiTi) can produce greater tooth movement over 12 weeks than single-strand superelastic NiTi. We found moderate-quality evidence that there is no difference in pain at day 1 between multistrand stainless steel versus superelastic NiTi arch wires. There is insufficient evidence from our included studies to know if any other particular initial arch wire material is better or worse than another, or if they function equally well, with regard to speed of straightening, pain or tooth shortening in people undergoing orthodontic treatment. There was moderate-quality evidence that coaxial superelastic NiTi can produce greater tooth movement than single-strand superelastic NiTi, and that there is no real difference in pain whether whether arch wires are made with multistrand stainless steel or superelastic NiTi. The quality of the evidence for all other comparisons and outcomes was low or very low. Overall, the evidence about initial arch wires in orthodontic treatment is very limited, with comparisons often assessed by one small study with problems in its design. The findings are imprecise and unreliable so more research is needed."
    },
    {
        "index": "cochrane-simplification-test-265",
        "sentence": "This review includes just one cluster-randomised study of 306 older people with dementia and an average age of 86 years, conducted across 16 nursing homes in France. The study did not measure any of our primary or secondary outcomes but did measure behavioural change using three measurement scales: the Cohen-Mansfield Agitation Inventory (CMAI; 29-item scale), the Neuropsychiatric Inventory (NPI; 12-item scale), and the Observation Scale (OS; 25-item scale). For the CMAI, the study reports a Global score (29 items rated on a seven-point scale (1 = never occurs to 7 = occurs several times an hour) and summed to give a total score ranging from 29 to 203) and mean scores (evaluable items (rated on the same 7-point scale) divided by the theoretical total number of items) for the following four domains: Physically Non-Aggressive Behaviour, such as pacing (13 items); Verbally Non-Aggressive Behaviour, such as repetition (four items); Physically Aggressive Behaviour, such as hitting (nine items); and Verbally Aggressive Behaviour, such as swearing (three items). Four of the five CMAI scales improved in the intervention group (Global: change mean difference (MD) \u22125.69 points, 95% confidence interval (CI) \u22129.59 to \u22121.79; Physically Non-Aggressive: change MD \u22120.32 points, 95% CI \u22120.49 to \u22120.15; Verbally Non-Aggressive: change MD \u22120.44 points, 95% CI \u22120.69 to \u22120.19; and Verbally Aggressive: change MD \u22120.16 points, 95% CI \u22120.31 to \u22120.01). There was no difference in change scores on the Physically Aggressive scale (MD \u22120.08 points, 95% CI \u22120.37 to 0.21). Using GRADE guidelines, we rated the quality of this evidence as very low due to high risk of bias and indirectness of the outcome measures. There were no differences in NPI or OS change scores between groups by the end of the study. We also identified one ongoing study. The limited evidence means that uncertainty remains around the effectiveness of de-escalation and the relative efficacy of different techniques. High-quality research on the effectiveness of this intervention is therefore urgently needed.",
        "gold": "We looked for all available evidence on this topic, finding just two studies. One of these included 306 people with dementia and an average age of 86 years, living in 16 nursing homes in France. The second study is still in progress and did not provide results for the review. The study did not assess areas important to us, such as the number of injuries sustained by staff or residents. It did, however, measure the impact of staff training on residents' level of aggression three months after the end of the training. Some measures of physical and verbal aggression showed reductions, but not all. The reliability of evidence available in the one included trial is very low and did not address important questions such as injury. Therefore, we cannot say whether de-escalation techniques are effective. The evidence is current to September 2017."
    },
    {
        "index": "cochrane-simplification-test-266",
        "sentence": "We included 13 trials with 1316 participants in a qualitative synthesis. Participants were incontinent for urine, stool, or both, and were residents in a nursing home or were hospitalised. Eleven trials had a small sample size and short follow-up periods. .The overall risk of bias in the included studies was high. The data were not suitable for meta-analysis due to heterogeneity in participant population, skin care products, skin care procedures, outcomes, and measurement tools. Nine trials compared different topical skin care products, including a combination of products. Two trials tested a structured skin care procedure. One trial compared topical skin care products alongside frequencies of application. One trial compared frequencies of application of topical skin care products. We found evidence in two trials, being of low and moderate quality, that soap and water performed poorly in the prevention and treatment of IAD (primary outcomes of this review). The first trial indicated that the use of a skin cleanser might be more effective than the use of soap and water (risk ratio (RR) 0.39, 95% confidence interval (CI) 0.17 to 0.87; low quality evidence). The second trial indicated that a structured skin care procedure, being a washcloth with cleansing, moisturising, and protecting properties, might be more effective than soap and water (RR 0.31, 95% CI 0.12 to 0.79; moderate quality evidence). Findings from the other trials, all being of low to very low quality, suggest that applying a leave-on product (moisturiser, skin protectant, or a combination) might be more effective than not applying a leave-on product. No trial reported on the third primary outcome 'number of participants not satisfied with treatment' or on adverse effects. Little evidence, of very low to moderate quality, exists on the effects of interventions for preventing and treating IAD in adults. Soap and water performed poorly in the prevention and treatment of IAD. Application of leave-on products (moisturisers, skin protectants, or a combination) and avoiding soap seems to be more effective than withholding these products. The performance of leave-on products depends on the combination of ingredients, the overall formulation and the usage (e.g. amount applied). High quality confirmatory trials using standardised, and comparable prevention and treatment regimens in different settings/regions are required. Furthermore, to increase the comparability of trial results, we recommend the development of a core outcome set, including validated measurement tools. The evidence in this review is current up to 28 September 2016.",
        "gold": "We included randomised controlled trials which compared skin care products, procedures, methods for using skin care products and frequencies of using a skin care product. The participants had to be over 18 years of age. We found thirteen, mostly small, trials, involving 1316 participants. All participants were incontinent for urine, stool, or both and lived in nursing homes or were hospitalised. The trials tested skin care products, procedures, and frequencies of using a skin care product. Two trials showed that soap and water performed poorly in the prevention and treatment of IAD. A skin cleanser or a washcloth with cleansing, moisturising and protecting properties may be more effective than soap and water. The findings from the other trials suggest that using a skin care product is more effective than withholding a skin care product. We found no evidence that one skin care product performed better than another. The trials did not report on adverse effects. The quality of the evidence was low. Eleven trials had small numbers of participants and were of short duration. The overall risk of bias was high. The trials included in this review tested skin care products, procedures and frequencies of using a skin care product. Very limited evidence exists on the effects of interventions for preventing and treating IAD in adults. Larger, long-term and well performed trials are required. Furthermore, we recommend the development of a list of outcomes which are important for patients and will guide researchers in their study. This list should include well developed tools to measure the items in order to obtain accurate results. The review authors searched for studies that had been published up to 28 September 2016."
    },
    {
        "index": "cochrane-simplification-test-267",
        "sentence": "We included seven RCTs with a total of 333 participants in our review. Three trials studied hospitalised patients, two trials were conducted in an outpatient setting, while the trial setting was unclear in two studies. Participants' ages ranged from two years to young adults. The type of antiviral, administration route, and treatment duration varied between the trials. The antivirals in the included studies were acyclovir, valomaciclovir and valacyclovir. Follow-up varied from 20 days to six months. The diagnosis of IM was based on clinical symptoms and laboratory parameters. The risk of bias for all included studies was either unclear or high risk of bias. The quality of evidence was graded as very low for all outcomes and so the results should be interpreted with caution. There were statistically significant improvements in the treatment group for two of the 12 outcomes. These improvements may be of limited clinical significance. There was a mean reduction in 'time to clinical recovery as assessed by physician' of five days in the treatment group but with wide confidence intervals (CIs) (95% CI -8.04 to -1.08; two studies, 87 participants). Prospective studies indicate that clinical signs and symptoms may take one month or more to resolve and that fatigue may be persistent in approximately 10% of patients at six-month follow-up, so this may not be a clinically meaningful result. Trial results for the outcome 'adverse events and side effects of medication' were reported narratively in only five studies. In some reports authors were unsure whether an adverse event was related to medication or complication of disease. These results could not be pooled due to the potential for double counting results but overall, the majority of trials reporting this outcome did not find any significant difference between treatment and control groups. There was a mean reduction in 'duration of lymphadenopathy' of nine days (95% CI -11.75 to -6.14, two studies, 61 participants) in favour of the treatment group. In terms of viral shedding, the overall effect from six studies was that viral shedding was suppressed while on antiviral treatment, but this effect was not sustained when treatment stopped. For all other outcomes there was no statistically significant difference between antiviral treatment and control groups. The effectiveness of antiviral agents (acyclovir, valomaciclovir and valacyclovir) in acute IM is uncertain. The quality of the evidence is very low. The majority of included studies were at unclear or high risk of bias and so questions remain about the effectiveness of this intervention. Although two of the 12 outcomes have results that favour treatment over control, the quality of the evidence of these results is very low and may not be clinically meaningful. Alongside the lack of evidence of effectiveness, decision makers need to consider the potential adverse events and possible associated costs, and antiviral resistance. Further research in this area is warranted.",
        "gold": "We included seven studies that involved a total of 333 people; two were conducted in Europe and five in the USA. Three studies took place in hospitals, one each in a student health centre and a children's clinic, but the setting was unclear in two studies. Three different antiviral drugs were studied: acyclovir, valomaciclovir and valacyclovir, as well as dosage, comparison treatment (fake or no treatment), and how long people were treated and followed up. One study did not report study funding, but the other six studies appeared to have some industry support. None declared conflicts of interest, but one included two authors from a drug company. We wanted to investigate several outcomes: time to recovery; medication side effects; duration of: fever, sore throat, swollen lymph nodes, enlarged spleen and liver; development of glandular fever complications; how long it took to eliminate the virus from the throat; health-related quality of life; days off school or work; and economic outcomes. We found improvements in participants who received antiviral for two outcomes. There was an improvement of five days in time taken to recover among people who received antiviral treatment, but this result was not very precise, and the way it was measured was not clearly defined. Other studies show that glandular fever symptoms can take a month or more to get better, and tiredness may occur in about one in every 10 of patients six months later. This improvement may be of limited clinical significance. Most studies that examined adverse effects did not find any differences between people who received antivirals and those who did not. Time taken to resolve lymph node swelling improved to nine days when antivirals were used. However, studies that reported on this, measured lymph node swelling in different ways so we cannot be sure about the accuracy of the result. Evidence quality was rated as very low for all results, which means that we cannot know the exact effect of using antivirals for glandular fever. Better studies are needed so we can draw firm conclusions."
    },
    {
        "index": "cochrane-simplification-test-268",
        "sentence": "This review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either insulin detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at the end of trial. Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups. The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups. Insulin detemir was associated with less weight gain. Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions. There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups. Our analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.",
        "gold": "Four studies investigated a total of 2250 people. Trials lasted between 24 and 52 weeks. Overall, risk of bias of the evaluated studies was high. Our analysis of these intermediate term trials comparing insulin detemir with insulin glargine showed that these two insulins were equally effective in achieving and maintaining glycaemic control (glycosylated haemoglobin A1c (HbA1c)). There were no differences in overall, nocturnal and severe hypoglycaemia when comparing insulin detemir to insulin glargine. Insulin detemir was associated with significantly less weight gain (one study showing a difference of 0.9 kg). Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions (1.8% of patients treated with insulin detemir compared to 0.4% of patients treated with insulin glargine had injection side reactions). There was no difference in the variability of fasting glucose levels or the variability of glucose values of 24-hour profiles between the two treatment groups. From the retrieved trials it was not possible to draw conclusions on the effects of these two insulins on quality of life, their costs or on the number of fatalities. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups. Our analyses suggest that there is no clinically relevant difference in the efficacy or the safety between the use of insulin detemir and insulin glargine for treating type 2 diabetes mellitus. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was only injected once-daily, with somewhat fewer injection site reactions."
    },
    {
        "index": "cochrane-simplification-test-269",
        "sentence": "Six crossover trials and two parallel group trials were included. Six trials assessed the effects of SNS for FI. In the parallel group trial conducted by Tjandra, 53 participants with severe FI in the SNS group experienced fewer episodes of faecal incontinence compared to the control group who received optimal medical therapy (mean difference (MD) \u22125.20, 95% confidence interval (CI) \u22129.15 to \u22121.25 at 3 months; MD \u22126.30, 95% CI \u221210.34 to \u22122.26 at 12 months). Adverse events were reported in a proportion of participants: pain at implant site (6%), seroma (2%) and excessive tingling in the vaginal region (9%). In the parallel group trial carried out by Thin, 15 participants with FI in the SNS group experienced fewer episodes of FI compared with the percutaneous tibial nerve stimulation (PTNS) group (MD \u22123.00, 95% CI \u22126.61 to 0.61 at 3 months; MD \u22123.20, 95% CI \u22127.14 to 0.74 at 12 months). Adverse events were reported in three participants: mild ipsilateral leg pain during temporary testing (n = 1); and stimulator-site pain following insertion of neurostimulator (n = 2). In the crossover trial by Leroi 7 of 34 recruited participants were excluded from the crossover due mainly to complications or immediate device failure. Twenty-four of the remaining 27 participants while still blinded chose the period of stimulation they had preferred. Outcomes were reported separately for 19 participants who preferred the 'on' and five who preferred the 'off' period. For the group of 19, the median (range) episodes of faecal incontinence per week fell from 1.7 (0 to 9) during the 'off' period to 0.7 (0 to 5) during the 'on' period; for the group of five, however, the median (range) rose from 1.7 (0 to 11) during the 'off' period compared with 3.7 (0 to 11) during the 'on' period. Four of 27 participants experienced an adverse event resulting in removal of the stimulator. In the crossover trial by S\u00f8rensen and colleagues, participants did not experience any FI episodes in either the one-week \u2018on\u2019 or \u2018off\u2019 periods. In the crossover trial by Vaizey, participants reported an average of six, and one, episodes of faecal incontinence per week during the 'off' and 'on' periods respectively in two participants with FI. Neither study reported adverse events. In the crossover trial by Kahlke, 14 participants with FI experienced significantly lower episodes of FI per week during the stimulator 'on' (1 (SD, 1.7)) compared with the 'off' period (8.4 (SD, 8.7)). Adverse events reported include: haematoma formation (n = 3); misplacement of tined lead (1); and pain at stimulator site (n = 1). Two trials assessed SNS for constipation. In the Kenefick trial, the two participants experienced an average of two bowel movements per week during the 'off' crossover period, compared with five during the 'on' period. Abdominal pain and bloating occurred 79% of the time during the 'off' period compared with 33% during the 'on' period. No adverse events occurred. In contrast, in the trial by Dinning with 59 participants, SNS did not improve frequency of bowel movements and 73 adverse events were reported, which included pain at site of the implanted pulse generator (32), wound infection (12), and urological (17) events. The limited evidence from the included trials suggests that SNS can improve continence in a proportion of patients with faecal incontinence. However, SNS did not improve symptoms in patients with constipation. In addition, adverse events occurred in some patients where these were reported. Rigorous high quality randomised trials are needed to allow the effects of SNS for these conditions to be assessed with more certainty.",
        "gold": "This review evaluated the published evidence for the use of SNS for patients with faecal incontinence or constipation from six trials of SNS for faecal incontinence (219 participants) and two trials of SNS for constipation (61 participants). Two of the faecal incontinence trials had a 'parallel group design', which means that one group of participants received SNS and the other control group did not receive SNS throughout the trial. The remaining six trials had a 'crossover design', in which the participants experienced equal periods with stimulation 'off' then 'on', or vice versa. The level of stimulation was such that participants could not tell whether the system was 'on' or 'off'. In the two 'parallel group' trials, 53 and 15 participants with faecal incontinence who were in the SNS group experienced fewer episodes of faecal incontinence compared to the control group at 3 and 12 months. In the first crossover trial, 24 participants who completed the trial chose the period of stimulation they had preferred while still unaware whether this was 'on' or 'off'. Nineteen participants who preferred the 'on' period experienced 59% fewer episodes of FI per week during the 'on' period, and 5 participants who preferred the 'off' period experienced 118% more episodes of FI per week. In the second crossover trial, the participants did not experience episodes of FI during either the 'on' or the 'off' periods. In the third trial, participants experienced 83% fewer episodes of faecal incontinence during the 'on' compared with the 'off' period. In the fourth crossover trial participants experienced 88% fewer episodes of faecal incontinence during the 'on' period compared with the 'off' period. \u2014adverse effects:Not all trials reported adverse effects after SNS. The two 'parallel group' trials reported only minor complications, in 10% of SNS participants in the first study, and in 3 participants in the second study. In the first crossover study 7 out of 34 participants were excluded from crossover due mainly to complications. Four out of 27 participants with an implanted system in this study experienced a problem that led to the device being removed. The participants in the fourth crossover trial experienced some complications with the SNS implanted electrode such as pain (one person), misplacement of the tined lead (one person) and haematoma (swelling containing blood) (three people). In one trial assessing SNS for constipation, two participants reported an increase of 150% in the frequency of passing stools per week, and time with abdominal pain and swelling went down from 79% during the 'off' period to 33% during the 'on' period. However, in the much larger second trial assessing SNS for constipation, in 59 participants SNS did not improve frequency of bowel movements. The limited evidence suggests that SNS can improve continence in some people with faecal incontinence. SNS did not improve symptoms in patients with constipation. Larger, good-quality trials are needed to provide more reliable evidence on the effectiveness of SNS for these two conditions."
    },
    {
        "index": "cochrane-simplification-test-270",
        "sentence": "Two trials (n = 190), at low risk of bias, were included in the review and both presented data on first time failure at the tooth level. Pooling of the data showed a statistically significant difference in favour of molar bands, with a hazard ratio of 2.92 (95% confidence intervals (CI) 1.80 to 4.72). No statistically significant heterogeneity was shown between the two studies. Data on first time failure at the patient level were also available and showed statistically different difference in favour of molar bands (risk ratio 2.30; 95% CI 1.56 to 3.41) (risk of event for molar tubes = 57%; risk of event for molar bands 25%). One trial presented data on decalcification again showing a statistically significant difference in favour of molar bands. No other adverse events identified. From the two well-designed and low risk of bias trials included in this review it was shown that the failure of molar tubes bonded with either a chemically-cured or light-cured adhesive was considerably higher than that of molar bands cemented with glass ionomer cement. One trial indicated that there was less decalcification with molar bands cemented with glass ionomer cement than with bonded molar tubes cemented with a light-cured adhesive. However, given there are limited data for this outcome, further evidence is required to draw more robust conclusions.",
        "gold": "The evidence in this review, which was carried out together with Cochrane Oral Health, is up-to-date as of 15 February 2017. We included two studies that evaluated 190 participants. Both trials were conducted in the UK and both compared bonded molar tubes with molar bands. From the limited data of two studies at low risk of bias, it would appear that bonded molar tubes are associated with a higher failure rate than with molar bands."
    },
    {
        "index": "cochrane-simplification-test-271",
        "sentence": "We identified 66 articles (published between 1988 and 2012) that were eligible according to the inclusion criteria. We collected the data on 7747 patients with gastric cancer who were staged with EUS. Overall the quality of the included studies was good: in particular, only five studies presented a high risk of index test interpretation bias and two studies presented a high risk of selection bias. For primary tumor (T) stage, results were stratified according to the depth of invasion of the gastric wall. The meta-analysis of 50 studies (n = 4397) showed that the summary sensitivity and specificity of EUS in discriminating T1 to T2 (superficial) versus T3 to T4 (advanced) gastric carcinomas were 0.86 (95% confidence interval (CI) 0.81 to 0.90) and 0.90 (95% CI 0.87 to 0.93) respectively. For the diagnostic capacity of EUS to distinguish T1 (early gastric cancer, EGC) versus T2 (muscle-infiltrating) tumors, the meta-analysis of 46 studies (n = 2742) showed that the summary sensitivity and specificity were 0.85 (95% CI 0.78 to 0.91) and 0.90 (95% CI 0.85 to 0.93) respectively. When we addressed the capacity of EUS to distinguish between T1a (mucosal) versus T1b (submucosal) cancers the meta-analysis of 20 studies (n = 3321) showed that the summary sensitivity and specificity were 0.87 (95% CI 0.81 to 0.92) and 0.75 (95% CI 0.62 to 0.84) respectively. Finally, for the metastatic involvement of lymph nodes (N-stage), the meta-analysis of 44 studies (n = 3573) showed that the summary sensitivity and specificity were 0.83 (95% CI 0.79 to 0.87) and 0.67 (95% CI 0.61 to 0.72), respectively. Overall, as demonstrated also by the Bayesian nomograms, which enable readers to calculate post-test probabilities for any target condition prevalence, the EUS accuracy can be considered clinically useful to guide physicians in the locoregional staging of people with gastric cancer. However, it should be noted that between-study heterogeneity was not negligible: unfortunately, we could not identify any consistent source of the observed heterogeneity. Therefore, all accuracy measures reported in the present work and summarizing the available evidence should be interpreted cautiously. Moreover, we must emphasize that the analysis of positive and negative likelihood values revealed that EUS diagnostic performance cannot be considered optimal either for disease confirmation or for exclusion, especially for the ability of EUS to distinguish T1a (mucosal) versus T1b (submucosal) cancers and positive versus negative lymph node status. By analyzing the data from the largest series ever considered, we found that the diagnostic accuracy of EUS might be considered clinically useful to guide physicians in the locoregional staging of people with gastric carcinoma. However, the heterogeneity of the results warrants special caution, as well as further investigation for the identification of factors influencing the outcome of this diagnostic tool. Moreover, physicians should be warned that EUS performance is lower in diagnosing superficial tumors (T1a versus T1b) and lymph node status (positive versus negative). Overall, we observed large heterogeneity and its source needs to be understood before any definitive conclusion can be drawn about the use of EUS can be proposed in routine clinical settings.",
        "gold": "We conducted a meta-analysis according to the most recent methods for diagnostic tests. The last literature search was performed in January 2015. We included 66 studies (of 7747 patients) in the review. We found that EUS can distinguish between superficial (T1 - T2) and advanced (T3 - T4) primary tumors with a sensitivity and a specificity greater than 85%. This performance is maintained for the discrimination between T1 and T2 superficial tumors. However, EUS diagnostic accuracy is lower when it comes to distinguishing between the different types of early tumors (T1a versus T1b) and between tumors with versus those without lymph node disease. Overall, EUS provides physicians with some helpful information on the stage of gastric cancer. Nevertheless, in the light of the variability of the results reported in the international medical literature, its limitations in terms of performance must be kept in mind in order to make the most out of the diagnostic potential of this tool. Finally, more work is needed to assess whether some technical improvements and the combination with other staging instruments may increase our ability to correctly stage the disease and thus optimize patient treatment."
    },
    {
        "index": "cochrane-simplification-test-272",
        "sentence": "We identified a total of six trials at high risk of bias involving 492 participants undergoing day-case laparoscopic cholecystectomy (n = 239) versus overnight stay laparoscopic cholecystectomy (n = 253) for symptomatic gallstones. The number of participants in each trial ranged from 28 to 150. The proportion of women in the trials varied between 74% and 84%. The mean or median age in the trials varied between 40 and 47 years. With regards to primary outcomes, only one trial reported short-term mortality. However, the trial stated that there were no deaths in either of the groups. We inferred from the other outcomes that there was no short-term mortality in the remaining trials. Long-term mortality was not reported in any of the trials. There was no significant difference in the rate of serious adverse events between the two groups (4 trials; 391 participants; 7/191 (weighted rate 1.6%) in the day-surgery group versus 1/200 (0.5%) in the overnight stay surgery group; rate ratio 3.24; 95% CI 0.74 to 14.09). There was no significant difference in quality of life between the two groups (4 trials; 333 participants; SMD -0.11; 95% CI -0.33 to 0.10). There was no significant difference between the two groups regarding the secondary outcomes of our review: pain (3 trials; 175 participants; MD 0.02 cm visual analogue scale score; 95% CI -0.69 to 0.73); time to return to activity (2 trials, 217 participants; MD -0.55 days; 95% CI -2.18 to 1.08); and return to work (1 trial, 74 participants; MD -2.00 days; 95% CI -10.34 to 6.34). No significant difference was seen in hospital readmission rate (5 trials; 464 participants; 6/225 (weighted rate 0.5%) in the day-surgery group versus 5/239 (2.1%) in the overnight stay surgery group (rate ratio 1.25; 95% CI 0.43 to 3.63) or in the proportion of people requiring hospital readmissions (3 trials; 290 participants; 5/136 (weighted proportion 3.5%) in the day-surgery group versus 5/154 (3.2%) in the overnight stay surgery group; RR 1.09; 95% CI 0.33 to 3.60). No significant difference was seen in the proportion of failed discharge (failure to be discharged as planned) between the two groups (5 trials; 419 participants; 42/205 (weighted proportion 19.3%) in the day-surgery group versus 43/214 (20.1%) in the overnight stay surgery group; RR 0.96; 95% CI 0.65 to 1.41). For all outcomes except pain, the accrued information was far less than the diversity-adjusted required information size to exclude random errors. Day-surgery appears just as safe as overnight stay surgery in laparoscopic cholecystectomy. Day-surgery does not seem to result in improvement in any patient-oriented outcomes such as return to normal activity or earlier return to work. The randomised clinical trials backing these statements are weakened by risks of systematic errors (bias) and risks of random errors (play of chance). More randomised clinical trials are needed to assess the impact of day-surgery laparoscopic cholecystectomy on the quality of life as well as other outcomes of patients.",
        "gold": "This review aims to investigate the current literature available and provides an overview of the evidence demonstrated in recent clinical trials on the subject. The review authors identified a total of six trials involving 492 participants. Two hundred and thirty-nine people underwent planned laparoscopic cholecystectomy as day-surgery and 253 participants stayed in the hospital overnight after the procedure. All the trials were at high risk of bias (methodological deficiencies that might make it possible to arrive at wrong conclusions by overestimating the benefit or underestimating the harm of the day-surgery or overnight stay procedure). We looked at outcomes that are considered to be important from the perspective of the participant and also the healthcare provider. These outcomes include death, serious complication, quality of life following procedure, pain, how long it took for people to return to normal activity and to return to work, hospital readmissions, and failed discharges (failure to be discharged as planned). There was no significant difference in the proportion who died or the complication rate between the group who underwent day-surgery and those who stayed overnight. Quality of life did not differ significantly between the two groups. There was no significant difference in the time taken for people to return to normal activity or to return to work. There was also no significant difference in the hospital readmission or failed discharge rates. The results suggest that day-surgery is safe for patients. It is important to note that all trials were at risk of bias and the data were sparse, resulting in a considerable chance of arriving at wrong conclusions due to systematic errors (overestimating benefits or underestimating harms of day-surgery or overnight stay) and random errors (play of chance). More randomised trials are needed to investigate the impact of day-surgery and overnight stay on the quality of life and other outcomes of people undergoing laparoscopic cholecystectomy."
    },
    {
        "index": "cochrane-simplification-test-273",
        "sentence": "We included eight studies, involving 2488 participants, two more studies and 415 more participants than the previous version of this review. Studies were of generally good methodological quality; we judged only one study at high risk of bias, due to small size. Two studies used a placebo control and six used 0.04% topical capsaicin as an 'active' placebo to help maintain blinding. Efficacy outcomes were inconsistently reported, resulting in analyses for most outcomes being based on less than complete data. For postherpetic neuralgia, we found four studies (1272 participants). At both 8 and 12 weeks about 10% more participants reported themselves much or very much improved with high-concentration capsaicin than with 'active' placebo; the point estimates of numbers needed to treat for an additional beneficial outcome (NNTs) were 8.8 (95% confidence interval (CI) 5.3 to 26) at 8 weeks and 7.0 (95% CI 4.6 to 15) at 12 weeks (2 studies, 571 participants; moderate quality evidence). More participants (about 10%) had average 2 to 8-week and 2 to 12-week pain intensity reductions over baseline of at least 30% and at least 50% with capsaicin than control, with NNT values between 10 and 12 (2 to 4 studies, 571 to 1272 participants; very low quality evidence). For painful HIV-neuropathy, we found two studies (801 participants). One study reported the proportion of participants who were much or very much improved at 12 weeks (27% with high-concentration capsaicin and 10% with 'active' placebo). For both studies, more participants (about 10%) had average 2 to 12-week pain intensity reductions over baseline of at least 30% with capsaicin than control, with an NNT of 11 (very low quality evidence). For peripheral diabetic neuropathy, we found one study (369 participants). It reported about 10% more participants who were much or very much improved at 8 and 12 weeks. One small study of 46 participants with persistent pain following inguinal herniorrhaphy did not show a difference between capsaicin and placebo for pain reduction (very low quality evidence). We downgraded the quality of the evidence for efficacy outcomes by one to three levels due to sparse data, imprecision, possible effects of imputation methods, and susceptibility to publication bias. Local adverse events were common, but not consistently reported. Serious adverse events were no more common with active treatment (3.5%) than control (3.2%). Adverse event withdrawals did not differ between groups, but lack of efficacy withdrawals were somewhat more common with control than active treatment, based on small numbers of events (six to eight studies, 21 to 67 events; moderate quality evidence, downgraded due to few events). No deaths were judged to be related to study medication. High-concentration topical capsaicin used to treat postherpetic neuralgia, HIV-neuropathy, and painful diabetic neuropathy generated more participants with moderate or substantial levels of pain relief than control treatment using a much lower concentration of capsaicin. These results should be interpreted with caution as the quality of the evidence was moderate or very low. The additional proportion who benefited over control was not large, but for those who did obtain high levels of pain relief, there were usually additional improvements in sleep, fatigue, depression, and quality of life. High-concentration topical capsaicin is similar in its effects to other therapies for chronic pain.",
        "gold": "We searched scientific databases for studies that looked at the effects of high-concentration capsaicin in adults who had moderate or severe neuropathic pain. The treatment had to have effects measured for at least 8 weeks. The evidence is current to June 2016. Eight studies satisfied our inclusion criteria, including two new studies for this update. The studies were well conducted. In seven studies, involving 2442 participants, we found that the treatment gave good levels of pain relief to a small number of participants with some types of neuropathic pain (pain after shingles, and nerve injury pain associated with HIV infection), and probably also in another type (painful feet because of damaged nerves caused by diabetes). About 4 in 10 people had at least moderate pain relief with capsaicin compared with 3 in 10 with control. The control was a treatment that looked the same but did not contain high levels of capsaicin, with either nothing added, or very small amounts of capsaicin added. In one small study (46 participants) in people with persistent pain after hernia surgery, it did not seem better than control. In all people who have this treatment there can be short-lived localised skin problems such as redness, burning, or pain. Serious problems seem to be uncommon, and were no more frequent in these trials with high-concentration capsaicin than with control using very low-concentration capsaicin or placebo. Slightly more people treated with control rather than capsaicin dropped out of the studies because of lack of benefit, but there was no difference between the groups for drop-outs because of side effects. We judged the quality of the evidence as moderate or very low for pain relief outcomes, mainly because only a small number of studies and moderate number of participants provided information for each outcome. We judged the quality of the evidence as moderate for harmful effects. Moderate quality means that further research may change the result. Very low quality means we are very uncertain about the results."
    },
    {
        "index": "cochrane-simplification-test-274",
        "sentence": "We included three trials involving 6343 participants. As the trials differed in the methods of measurement of carotid stenosis and in the definition of stroke, we did a pooled analysis of individual patient data on 6092 participants (35,000 patient years of follow-up), after reassessing the carotid angiograms and outcomes from all three trials using the primary electronic data files, and redefined outcome events where necessary, to achieve comparability. On re-analysis, there were no significant differences between the trials in the risks of any of the main outcomes in either of the treatment groups, or in the effects of surgery. Surgery increased the five-year risk of ipsilateral ischaemic stroke in participants with less than 30% stenosis (N = 1746, risk ratio (RR) 1.27, 95% confidence interval (CI) 0.80 to 2.01), had no significant effect in participants with 30% to 49% stenosis (N = 1429, RR 0.93, 95%CI 0.62 to 1.38), was of benefit in participants with 50% to 69% stenosis (N = 1549, RR 0.84, 95%CI 0.60 to 1.18), and was highly beneficial in participants with 70% to 99% stenosis without near-occlusion (N = 1095, RR 0.47, 95%CI 0.25 to 0.88). However, there was no evidence of benefit (N = 271, RR 1.03, 95%CI 0.57 to 1.84) in participants with near-occlusions. Ipsilateral ischaemic stroke describes insufficient blood flow to the cerebral hemisphere, secondary to same side severe stenosis of the internal carotid artery. Endarterectomy was of some benefit for participants with 50% to 69% symptomatic stenosis (moderate-quality evidence), and highly beneficial for those with 70% to 99% stenosis without near-occlusion (moderate-quality evidence). We found no benefit in people with carotid near-occlusion (high-quality evidence).",
        "gold": "This review identified three randomised controlled trials (6343 participants randomised), which compared carotid surgery with no carotid surgery (i.e. best medical therapy plus surgery versus best medical therapy alone) in participants with carotid stenosis and recent transient ischaemic attacks (TIA) or minor ischaemic strokes in the territory of that artery. The trials were carried out in Europe, USA, and Canada and included some centres in Israel, South Africa, and Australia. The gender ratio of participants was 2.6:1 (72% men and 28% women); 90% of participants were younger than 75 years old. The results of the three trials were initially conflicting because they differed in how they measured carotid stenosis and how they defined the outcomes. To address this discrepancy, we reassessed the patient data using the same methods and definitions, so results could be compared. The results of the review are current up to July 2016. Results showed that older male participants with 70% to 99% stenosis, without occlusion, and recent (within two weeks) TIA or stroke, had the most benefit from surgery, assuming they were well enough for surgery, and their surgeons had a record of low complication rates (less than 7% risk of stroke and death). Carotid endarterectomy also benefited participants with 50% to 99% carotid stenosis and symptoms. For participants whose carotid artery was nearly occluded, benefit was uncertain in the long term. Surgery tended to harm participants with less than 30% stenosis. The second European Carotid Surgery Trial, which is currently recruiting participants, is exploring whether a lipid lowering agent (statin) might be a better choice than carotid endarterectomy to prevent ischaemic stroke in ipsilateral carotid stenosis, which may benefit those who did not benefit from surgery in these trials. We found the evidence to be high quality for near occlusion and less than 30% carotid stenosis; and moderate quality for 50% to 99% carotid stenosis for any stroke or operative death, as well as ipsilateral ischaemic stroke and any operative stroke or death outcome."
    },
    {
        "index": "cochrane-simplification-test-275",
        "sentence": "Randomized controlled trials (RCT) Only one RCT met the inclusion criteria. The participants underwent enterostomy placement in the frame of an operation for: rectal cancer (37/60), ulcerative colitis (14/60), familial adenomatous polyposis (7/60), and other (2/60). The results between the lateral pararectal and the transrectal approach groups were inconclusive for the incidence of parastomal herniation (risk ratio (RR) 1.34, 95% confidence interval (CI) 0.40 to 4.48; low-quality evidence); development of ileus or stenosis (RR 2.0, 95% CI 0.19 to 20.9; low-quality evidence); or skin irritation (RR 0.67, 95% CI 0.21 to 2.13; moderate-quality evidence). The results were also inconclusive for the subgroup analysis in which we compared the effect of ileostomy versus colostomy on parastomal herniation. The study did not measured other stoma-related morbidities, or stoma-related mortality, but did measure quality of life, which was not one of our outcomes of interest. Non-randomized studies (NRS) Ten retrospective cohort studies, with a total of 864 participants, met the inclusion criteria. The indications for enterostomy placement and the baseline characteristics of the participants (age, co-morbidities, disease-severity) varied between studies. All included studies reported results for the primary outcome (parastomal herniation) and one study also reported data on one of the secondary outcomes (stomal prolapse). The effects of different surgical approaches on parastomal herniation (RR 1.22, 95% CI 0.84 to 1.75; 10 studies, 864 participants; very low-quality evidence) and the occurrence of stomal prolapse (RR 1.23, 95% CI 0.39 to 3.85; 1 study, 145 participants; very low-quality evidence) are uncertain. None of the included studies measured other stoma-related morbidity or stoma-related mortality. The present systematic review of randomized and non-randomized studies found inconsistent results between the two compared interventions regarding their potential to prevent parastomal herniation. In conclusion, there is still a lack of high-quality evidence to support the ideal surgical technique of stoma formation. The available moderate-, low-, and very low-quality evidence, does not support or refute the superiority of one of the studied stoma formation techniques over the other.",
        "gold": "The evidence is current to 9 November 2018. In this update, we included 10 retrospective cohort studies with a total of 864 participants, and one randomized controlled trial (RCT: a study in which participants are randomly allocated to the treatment groups), including 60 participants. The target population was individuals, regardless of age, who received a temporary or permanent enterostomy for any reason in either the elective (planned) or the emergency setting. The results found inconclusive results between the two techniques for the risk of parastomal herniation (11 studies, 924 participants), stomal prolapse (1 study, 145 participants), ileus or stenosis (1 study, 60 participants), and skin irritation (1 study, 60 participants). Neither technique was found to be better than the other for any of the stoma-related outcomes of interest. None of the studies measured other stoma-related problems, or death. We downgraded the quality of the evidence to moderate, low, or very low, because of high risk of bias, small sample sizes, few events, and diversity across studies. Based on the current knowledge presented in this review, there is no evidence to support the use of one stoma formation technique over the other. Further research is likely to have an important impact on our confidence in the estimate of effect."
    },
    {
        "index": "cochrane-simplification-test-276",
        "sentence": "Four new trials were added after the 2012 search. The review now includes 24 relevant studies, with 2126 participants. Overall, the evidence was very low quality. We found no significant differences in the primary outcomes of relapse, hospitalisation and general functioning between supportive therapy and standard care. There were, however, significant differences favouring other psychological or psychosocial treatments over supportive therapy. These included hospitalisation rates (4 RCTs, n = 306, RR 1.82 CI 1.11 to 2.99, very low quality of evidence), clinical improvement in mental state (3 RCTs, n = 194, RR 1.27 CI 1.04 to 1.54, very low quality of evidence) and satisfaction of treatment for the recipient of care (1 RCT, n = 45, RR 3.19 CI 1.01 to 10.7, very low quality of evidence). For this comparison, we found no evidence of significant differences for rate of relapse, leaving the study early and quality of life. When we compared supportive therapy to cognitive behavioural therapy CBT), we again found no significant differences in primary outcomes. There were very limited data to compare supportive therapy with family therapy and psychoeducation, and no studies provided data regarding clinically important change in general functioning, one of our primary outcomes of interest. There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy but these findings are based on a few small studies where we graded the evidence as very low quality. Future research would benefit from larger trials that use supportive therapy as the main treatment arm rather than the comparator.",
        "gold": "The aim of this review is to assess the effectiveness of supportive therapy compared to other specific therapies or treatment as usual. This update is based on a search run in 2012; the review now includes 24 randomised studies with a total of 2126 people. The studies compared supportive therapy either with standard care alone or a range of other therapies such as CBT, family therapy and psychoeducation. The participants continued to receive their antipsychotic medication and any other treatment they would normally receive during the trials. Overall, the quality of evidence from these studies was very low. There is not enough information or data to identify any real therapeutic difference between supportive therapy and standard care. There are several outcomes, including hospitalisation, satisfaction with treatment and general mental state, indicating advantages for other psychological therapies over supportive therapy. However, these findings are limited because they are based on only a few small studies where the quality of evidence is very low. There was very limited information to compare supportive therapy with family therapy and psychoeducation as most studies in this review focused on other psychological therapies, such as CBT. Apart from one study presenting data on death, there was no information on the adverse effects of supportive therapy. In summary, there does not seem to be much difference between supportive therapy, standard care and other therapies. Future research would benefit from larger studies where supportive therapy is the main treatment. Ben Gray, Senior Peer Researcher, McPin Foundation: http://mcpin.org/"
    },
    {
        "index": "cochrane-simplification-test-277",
        "sentence": "Eleven studies satisfied inclusion criteria, lasting one week or longer; 949 participants with mostly moderate or severe pain were randomised initially, but fewer completed treatment or had results of treatment. Eight studies were double-blind, two single-blind, and one open-label. None had a placebo only control; eight compared different NSAIDs, three an NSAID with opioid or opioid combination, and one both. None compared an NSAID plus opioid with the same dose of opioid alone. Most studies were at high risk of bias for blinding, incomplete outcome data, or small size; none was unequivocally at low risk of bias. It was not possible to compare NSAIDs as a group with another treatment, or one NSAID with another NSAID. Results for all NSAIDs are reported as a randomised cohort. We judged results for all outcomes as very low-quality evidence. None of the studies reported our primary outcomes of participants with pain reduction of at least 50%, and at least 30%, from baseline; participants with Patient Global Impression of Change (PGIC) of much improved or very much improved (or equivalent wording). With NSAID, initially moderate or severe pain was reduced to no worse than mild pain after one or two weeks in four studies (415 participants in total), with a range of estimates between 26% and 51% in individual studies. Adverse event and withdrawal reporting was inconsistent. Two serious adverse events were reported with NSAIDs, and 22 deaths, but these were not clearly related to any pain treatment. Common adverse events were thirst/dry mouth (15%), loss of appetite (14%), somnolence (11%), and dyspepsia (11%). Withdrawals were common, mostly because of lack of efficacy (24%) or adverse events (5%). There is no high-quality evidence to support or refute the use of NSAIDs alone or in combination with opioids for the three steps of the three-step WHO cancer pain ladder. There is very low-quality evidence that some people with moderate or severe cancer pain can obtain substantial levels of benefit within one or two weeks.",
        "gold": "In this review we set out to examine the evidence on how well NSAIDs worked (alone or with morphine-like drugs) in adults with cancer pain. We also wanted to know how many people had side effects, and how severe they were. In April 2017, we found 11 studies with 949 participants. They compared NSAID with NSAID, or NSAID with opioid drug (morphine or codeine). No studies looked at using NSAID together with an opioid-like morphine, which is how they are often used. The studies were small and of poor quality. They used different designs and different ways of showing their pain results. Outcomes important to people with cancer pain were often not reported. Many different NSAIDs were tested, and it was not possible to make sensible comparisons. With an NSAID, initially moderate or severe cancer pain was reduced to no worse than mild pain after one or two weeks in 1 in 4 (26%) to 1 in 2 (51%) people in four studies. Side-effect reporting was poor. Two serious side effects were reported with NSAIDs, and 22 deaths, but these were not related to pain treatment. Common side effects were thirst/dry mouth (1 in 7; 15%), loss of appetite (1 in 7; 14%), sleepiness (1 in 10; 11%), and heartburn (1 in 10; 11%). One in four people stopped taking NSAIDs because the drug did not work, and 1 in 20 stopped because of side effects. The quality of the evidence was very low. Very low-quality evidence means that we are very uncertain about the impact of an NSAID alone for treating cancer pain. We do not know whether using NSAIDs together with an opioid such as codeine or morphine is worthwhile."
    },
    {
        "index": "cochrane-simplification-test-278",
        "sentence": "Two studies comprising 287 participants were included. One study (with an overall unclear to high risk of bias) involved 253 participants and the quality of the evidence for most outcomes was very low. This study, reported that pain severity at day two and day three was lower in the tinzaparin group than in the placebo group (P < 0.01, analysis of variance (ANOVA)) and additionally at day 4 (P < 0.05 (ANOVA)). Thus tinzaparin resulted in more rapid resolution of pain, as measured with a numerical pain scale. The mean difference in duration of painful crises was statistically significant at -1.78 days in favour of the tinzaparin group (95% confidence interval -1.94 to -1.62). Participants treated with tinzaparin had statistically significantly fewer hospitalisation days than participants in the group treated with placebo, with a mean difference of -4.98 days (95% confidence interval -5.48 to -4.48). Two minor bleeding events were reported as adverse events in the tinzaparin group, and none were reported in the placebo group. The second study (unclear risk of bias) including 34 participants and was a conference abstract with limited data and only addressed one of the predefined outcomes of the review; i.e. pain intensity. After one day pain intensity reduced more, as reported on a visual analogue scale, in the dalteparin group than in the placebo group, mean difference -1.30 (95% confidence interval -1.60 to -1.00), with the quality of evidence rated very low. The most important reasons for downgrading the quality of evidence were serious risk of bias and imprecision (due to low sample size or low occurrence of events). Based on the results of two studies, evidence is incomplete to support or refute the effectiveness of low-molecular-weight heparins in people with sickle cell disease. Vaso-occlusive crises are extremely debilitating for sufferers of sickle cell disease; therefore well-designed placebo-controlled studies with other types of low-molecular-weight heparins, and in participants with different genotypes of sickle cell disease, still need to be carried out to confirm or dismiss the results of this single study.",
        "gold": "The review included two studies that lasted seven days with a total of 287 people. One study involved 253 people (aged approximately 22 years) with sickle cell disease and compared tinzaparin with placebo and people were selected for one treatment or the other randomly. The other study was smaller with 34 participants (aged approximately 27 years) and compared dalteparin versus placebo. Tinzaparin reduced the number of days spent in hospital and reduced the pain (and the intensity of the pain) more rapidly. Two minor bleedings were reported in the tinzaparin group versus none in the placebo group. The data regarding the effectiveness of dalteparin were very limited and only addressed pain intensity, being more reduced by treatment with dalteparin than by placebo. These data are not sufficient to support the conclusion that low-molecular-weight heparins are effective in the treatment of vaso-occlusive crises in people with sickle cell disease. Additional studies with different types of low-molecular-weight heparin used in different forms of sickle cell disease, are necessary to confirm or dismiss the results of this single study. Vaso-occlusive crises can be extremely debilitating and can have a significant impact on quality of life; therefore it is important to know whether low-molecular-weight heparins might serve as a useful treatment option with few side effects. The quality of the evidence for the majority of outcomes was very low, this had mainly to do with risk of bias of the studies (e.g. method of blinding unclear) or with small sample size of the studies."
    },
    {
        "index": "cochrane-simplification-test-279",
        "sentence": "We did not find any completed randomised trials. Comparing antiplatelets with anticoagulants across 36 observational studies (1285 patients), there were no significant differences in the odds of death (Peto odds ratio (Peto OR) 2.02, 95% CI 0.62 to 6.60), or the occurrence of ischaemic stroke (OR 0.63, 95% CI 0.21 to 1.86) (34 studies, 1262 patients). For the outcome of death or disability, there was a non-significant trend in favour of anticoagulants (OR 1.77, 95% CI 0.98 to 3.22; P = 0.06) (26 studies, 463 patients). Symptomatic intracranial haemorrhages (5/627; 0.8%) and major extracranial haemorrhages (7/425; 1.6%) occurred only in the anticoagulation group; however, for both these outcomes, the estimates were imprecise and indicated no significant difference between the two treatment modalities. There were no randomised trials comparing either anticoagulants or antiplatelet drugs with control, thus there is no evidence to support their routine use for the treatment of extracranial internal carotid artery dissection. There were also no randomised trials that directly compared anticoagulants with antiplatelet drugs and the reported non-randomised studies did not show any evidence of a significant difference between the two.",
        "gold": "We did not find any completed randomised trials testing these drugs in people with carotid artery dissection. However, there is one ongoing trial. We found only poor quality non-randomised studies that compared anticoagulants with aspirin. There was no evidence that anticoagulants were better than aspirin. Aspirin is likely to be similarly effective and safe as anticoagulants in such patients. More research is needed."
    },
    {
        "index": "cochrane-simplification-test-280",
        "sentence": "We identified 26 RCTs (2066 patients). Heterogeneity of treatments and outcomes precluded meta-analysis. We grouped results according to wound type, and silver preparation. Burns Thirteen trials compared topical silver (in a variety of formulations - including silver sulphadiazine (SSD) cream) with non-silver dressings. One trial showed fewer infections with silver nitrate when compared with a non-silver dressing, but three trials showed significantly more infection with SSD than with the non-silver dressing. Six trials compared SSD cream with silver-containing dressings. One showed significantly fewer infections with the silver-containing dressing (Hydron AgSD) compared with SSD, the remaining five found no evidence of a difference. One trial compared two silver-containing dressings, and showed a significantly lower infection rate with silver-coated gauze (Acticoat\u00ae) than with silver nitrate gauze. Other wounds Six trials compared SSD/silver-containing dressings with non-silver dressings (nine dressings in total). Most comparisons (seven) found no significant differences in infection rates; one trial in a variety of wounds exhibited significantly fewer infections with SSD/hydrocolloid, but another, in acute wounds, found significantly more infections with SSD. Only one comparison showed a significant reduction in healing time associated with a silver-containing hydrofibre dressing in diabetic foot ulcers. There is insufficient evidence to establish whether silver-containing dressings or topical agents promote wound healing or prevent wound infection; some poor quality evidence for SSD suggests the opposite.",
        "gold": "This review identified 26 trials (involving 2066 participants) comparing silver-containing dressings or creams against dressings or creams that did not contain silver. Twenty of the trials were on burn wounds, while the other trials were on a mixture of wound types. Most studies were small and of poor quality. After examining them all, the authors concluded that there is not enough evidence to support the use of silver-containing dressings or creams, as generally these treatments did not promote wound healing or prevent wound infections. Some evidence from a number of small, poor-quality studies suggested that one silver-containing compound (silver sulphadiazine) has no effect on infection, and actually slows down healing in patients with partial-thickness burns."
    },
    {
        "index": "cochrane-simplification-test-281",
        "sentence": "We included 12 studies with 3571 participants. All included studies examined the empiric use of one antimicrobial regimen versus another for the treatment of adults with VAP, but the particular drug regimens examined by each study varied. There was potential for bias because some studies did not report outcomes for all participants. All but one study reported sources of funding or author affiliations with pharmaceutical companies. We found no statistical difference in all-cause mortality between monotherapy and combination therapy (N = 4; odds ratio (OR) monotherapy versus combination 0.97, 95% confidence interval (CI) 0.73 to 1.30), clinical cure (N = 2; OR monotherapy versus combination 0.88, 95% CI 0.56 to 1.36), length of stay in ICU (mean difference (MD) 0.65, 95% CI 0.07 to 1.23) or adverse events (N = 2; OR monotherapy versus combination 0.93, 95% CI 0.68 to 1.26). We downgraded the quality of evidence for all-cause mortality, adverse events, and length of ICU stay to moderate for this comparison. We determined clinical cure for this comparison to be of very low-quality evidence. For our second comparison of combination therapy with optional adjunctives only one meta-analysis could be performed due to a lack of trials comparing the same antibiotic regimens. Two studies compared tigecycline versus imipenem-cilastatin for clinical cure in the clinically evaluable population and there was a statistically significant increase in clinical cure for imipenem-cilastatin (N = 2; OR tigecycline versus imipenem-cilastatin 0.44, 95% CI 0.23 to 0.84). Of importance, this effect was due to a single study. We found no statistical difference in all-cause mortality between carbapenem and non-carbapenem therapies (N = 1; OR carbapenem versus non-carbapenem 0.59, 95% CI 0.30 to 1.19) or adverse events (N = 3; OR carbapenem versus non-carbapenem 0.78, 95% CI 0.56 to 1.09), but we found that carbapenems are associated with a statistically significant increase in the clinical cure (N = 3; OR carbapenem versus non-carbapenem 1.53, 95% CI 1.11 to 2.12 for intention-to-treat (ITT) analysis and N = 2; OR carbapenem versus non-carbapenem 2.29, 95% CI 1.19 to 4.43 for clinically evaluable patients analysis). For this comparison we downgraded the quality of evidence for mortality, and clinical cure (ITT and clinically evaluable populations) to moderate. We determined the quality of evidence for adverse events to be low. We did not find a difference between monotherapy and combination therapy for the treatment of people with VAP. Since studies did not identify patients with increased risk for multidrug-resistant bacteria, these data may not be generalisable to all patient groups. However, this is the largest meta-analysis comparing monotherapy to multiple antibiotic therapies for VAP and contributes further evidence to the safety of using effective monotherapy for the empiric treatment of VAP. Due to lack of studies, we could not evaluate the best antibiotic choice for VAP, but carbapenems as a class may result in better clinical cure than other tested antibiotics.",
        "gold": "We looked at studies involving adults aged over 18 years who were treated in intensive care units for ventilator-associated pneumonia and needed antibiotic treatment. We analysed 12 studies with 3571 participants. All included studies looked at the use of one antibiotic treatment plan versus another, but these varied among studies. There was potential for bias because some studies did not report outcomes for all participants, and funding for many was provided by pharmaceutical companies and study authors were affiliated with these companies. We used statistical techniques to evaluate our results. For single versus multiple antibiotics, we found no difference in rates of death or cure, or adverse events. For our comparison of combination therapies with optional adjunctives we were only able to analyse clinical cure for one the antibiotics Tigecycline and imipenem-cilastatin for which imipenem-cilastatin was found to have higher clinica cure. We also looked at carbapenem (antibiotics used to treat infections caused by multidrug-resistant bacteria) versus non-carbapenem treatment; we found no difference in death rate or adverse effects, but we found that carbapenems are associated with an increase in clinical cure. We assessed evidence quality as moderate for most outcomes, and very low for clinical cure when single-antibiotic treatment was compared with multiple antibiotic therapy. We also found that evidence quality was low for adverse events when carbapenem was compared with non-carbapenem treatment. We did not find differences between single and combination therapy, lending support to use of a single-antibiotic treatment plan for people with ventilator-associated pneumonia. This may not be applicable to all patients because studies did not identify patients who are at risk of exposure to harmful types of bacteria. We could not evaluate the best single-antibiotic choice to treat people with ventilator-associated pneumonia because there were too few studies, but carbapenems may achieve better cure rates than other tested antibiotics."
    },
    {
        "index": "cochrane-simplification-test-282",
        "sentence": "We included 29 ITS analyses (12 were controlled) investigating policies targeting 11 drug classes for restriction. Participants were most often senior citizens or low income adult populations, or both, in publically subsidized or administered pharmaceutical benefit plans.\u00a0Impact of policies varied by drug class and whether restrictions were implemented or relaxed. When policies targeted gastric-acid suppressant and non-steroidal anti-inflammatory drug classes, decreased drug use and substantial savings on drugs occurred immediately and for up to two years afterwards, with no increase in the use of other health services (6 studies). Targeting second generation antipsychotic drugs increased treatment discontinuity and the use of other health services without reducing overall drug expenditures (2 studies). Relaxing restrictions for reimbursement of antihypertensives and statins increased appropriate use and decreased overall drug expenditures. Two studies which measured health outcomes directly were inconclusive. Implementing restrictions to coverage and reimbursement of selected medications can decrease third-party drug spending without increasing the use of other health services (6 studies). Relaxing reimbursement rules for drugs used for secondary prevention can also remove barriers to access. Policy design, however, needs to be based on research quantifying the harm and benefit profiles of target and alternative drugs to avoid unwanted health system and health effects. Health impact evaluation should be conducted where drugs are not interchangeable. Impacts on health equity, relating to the fair and just distribution of health benefits in society (sustainable access to publically financed drug benefits for seniors and low income populations, for example), also require explicit measurement.",
        "gold": "This review found 29 studies that evaluated policies that restrict reimbursement of specific prescriptions drugs. Where drugs have cheaper, effective alternatives and they target symptoms, this review found that reimbursement restriction polices can ensure better use of the medications with reduced costs and without an increase in the use of other health services, as would be expected if there were negative health effects of the restriction policies. Evaluation is required if alternative drugs are not effective substitutes. Removing restrictions for drugs that prevent complications of disease can result in an intended increase in their use as well as cost savings. When restrictions to reimbursement policies are designed using the best available evidence on the health impact of the medications, they support equitable access to the drugs that best support health by supporting the sustainability of publically subsidized drug plans. A summary of this review for policy-makers is availablehere"
    },
    {
        "index": "cochrane-simplification-test-283",
        "sentence": "Nineteen studies met the criteria for inclusion in the review with data available for a total of 4232 participants. The included studies reported a wide variety of interventions, study populations, clinical outcomes and outcome measures. There was substantial clinical heterogeneity amongst the studies and it was not deemed appropriate to pool data in a meta-analysis. We summarised data by categorising similar interventions into comparison groups. Comparison 1: Any form of one-to-one OHA versus no OHA Four studies compared any form of one-to-one OHA versus no OHA. Two studies reported the outcome of gingivitis. Although one small study had contradictory results at 3 months and 6 months, the other study showed very low-quality evidence of a benefit for OHA at all time points (very low-quality evidence). The same two studies reported the outcome of plaque. There was low-quality evidence that these interventions showed a benefit for OHA in plaque reduction at all time points. Two studies reported the outcome of dental caries at 6 months and 12 months respectively. There was very low-quality evidence of a benefit for OHA at 12 months. Comparison 2: Personalised one-to-one OHA versus routine one-to-one OHA Four studies compared personalised OHA versus routine OHA. There was little evidence available that any of these interventions demonstrated a difference on the outcomes of gingivitis, plaque or dental caries (very low quality). Comparison 3: Self-management versus professional OHA Five trials compared some form of self-management with some form of professional OHA. There was little evidence available that any of these interventions demonstrated a difference on the outcomes of gingivitis or plaque (very low quality). None of the studies measured dental caries. Comparison 4: Enhanced one-to-one OHA versus one-to-one OHA Seven trials compared some form of enhanced OHA with some form of routine OHA. There was little evidence available that any of these interventions demonstrated a difference on the outcomes of gingivitis, plaque or dental caries (very low quality). There was insufficient high-quality evidence to recommend any specific one-to-one OHA method as being effective in improving oral health or being more effective than any other method. Further high-quality randomised controlled trials are required to determine the most effective, efficient method of one-to-one OHA for oral health maintenance and improvement. The design of such trials should be cognisant of the limitations of the available evidence presented in this Cochrane Review.",
        "gold": "Authors from Cochrane Oral Health carried out this review and the evidence is up to date to 10 November 2017. We included research where individual patients received oral hygiene advice from a dental care professional on a one-to-one basis in a dental clinic setting with a minimum of 8 weeks follow-up. In total, within the identified 19 studies, oral hygiene advice was provided by a hygienist in eight studies, dentist in four studies, dental nurse in one study, dentist or hygienist in one study, dental nurse and hygienist in one study, and dental nurse oral hygiene advice to the control group with further self-administration of the intervention in one study. It was unclear in three of the studies which member of the dental team carried out the intervention. Over half of the studies (10 of the 19) were conducted in a hospital setting, with only five studies conducted in a general dental practice setting (where oral hygiene advice is largely delivered). Overall we found insufficient evidence to recommend any specific method of one- to-one oral hygiene advice as being more effective than another in maintaining or improving oral health. The studies we found varied considerably in how the oral hygiene advice was delivered, by whom and what outcomes were looked at. Due to this it was difficult to readily compare these studies and further well designed studies should be conducted to give a more accurate conclusion as to the most effective method of maintaining or improving oral health through one-to-one oral hygiene advice delivered by a dental care professional in a dental setting. We judged the quality of the evidence to be very low due to problems with the design of the studies."
    },
    {
        "index": "cochrane-simplification-test-284",
        "sentence": "Five small trials were included: two trials (30 and 49 participants) of oral steroids or placebo; one trial (40 participants) of oral steroids or no treatment; one trial (28 participants) of oral or intra-articular steroids; and one trial (32 participants) of manipulation under anaesthesia and intraarticular steroid injection with or without oral steroids. Study participants were similar across trials, but no trial used the same oral steroid regimen or dosage. Trials were of variable quality (only one of high quality) and some were poorly reported. No meta-analyses could be performed as no raw data could be extracted from one placebo-controlled trial and three trials used different comparators. One trial reported significant short-term benefits of oral steroids versus placebo: 48% more participants reported success (RR = 2 (95% CI 1.3 to 3.1, NNT=2); overall improvement in pain 2.7 (95% CI 1.4 to 4.0) on a 0 to 10 point scale; total shoulder abduction increased by 23.3 degrees (95% CI 11.3 to 35.3); Shoulder Pain and Disability Index (SPADI) score improved by 18.1 (95% CI 7.6 to 28.6) on a 0 to 100 point scale. But benefits were not maintained at 6 weeks. A second trial reported no significant differences between oral steroid and placebo in pain or range of movement but it suggested improvement occurred earlier in the steroid treated group. A third trial reported that oral steroids provided a more rapid initial improvement in pain compared to no treatment but negligible differences by five months. There were minimal adverse effects reported. Available data from two placebo-controlled trials and one no-treatment controlled trial provides \"Silver\" level evidence (www.cochranemsk.org) that oral steroids provides significant short-term benefits in pain, range of movement of the shoulder and function in adhesive capsulitis but the effect may not be maintained beyond six weeks.",
        "gold": "The studies tested people who had adhesive capsulitis for about 6 months. They were given no treatment, fake treatments, steroid injections or oral steroids. Oral steroids, such as prednisolone or cortisone were given for about 3 to 4 weeks, and sometimes again for another 3 to 4 weeks if people still had pain and stiffness. All people had physiotherapy or an exercise programme while taking the steroids. Benefits of oral steroids  In people with adhesive capsulitis, at 3 weeks, oral steroids may work more than fake pills \u00ad48 out of 100 people who took fake pills said they were better  \u00ad96 out of 100 people who took steroids said they were better may decrease pain and disability more than fake pills \u00adpain may decrease by 2.7 more points on a scale of 0 to 10 with steroids  \u00addisability may decrease by 18 more points on a scale of 0 to 100 with steroids may increase the ability to move the shoulder more than fake pills \u00adshoulder movement increased by 23 degrees  But these benefits did not last as long as 6 weeks so there is not enough evidence to be certain of the results beyond 3 weeks. Oral steroids may also improve pain earlier and quicker than no treatment at all. But after 5 months there were no benefits of oral steroids over no treatment. There is also not enough evidence to be certain of the results. Harms of oral steroids  In people with adhesive capsulitis who have no serious other problems, taking oral steroids for a short time may not cause serious side effects. But there is not enough evidence to be certain. Other research about steroids taken over longer periods of time shows that harms could include high cholesterol and high blood pressure."
    },
    {
        "index": "cochrane-simplification-test-285",
        "sentence": "Three randomised, placebo-controlled trials with a total of 50 participants were included in the review. All three trials compared rTMS with sham TMS. All the trials were of poor methodological quality and were insufficiently homogeneous to allow the pooling of results. Moreover, the high rate of attrition further increased the risk of bias. None of the trials provided detailed data on the ALS Functional Rating Scale-Revised (ALSFRS-R) scores at six months follow-up which was pre-assigned as our primary outcome. One trial contained data in a suitable form for quantitative analysis of our secondary outcomes. No difference was seen between rTMS and sham rTMS using the ALSFRS-R scores and manual muscle testing (MMT) scores at 12 months follow-up in this trial. Additionally, none of the trials reported any adverse events associated with the use of rTMS. However, in view of the small sample size, the methodological limitations and incomplete outcome data, treatment with rTMS cannot be judged as completely safe. There is currently insufficient evidence to draw conclusions about the efficacy and safety of rTMS in the treatment of ALS. Further studies may be helpful if their potential benefit is weighed against the impact of participation in a randomised controlled trial on people with ALS.",
        "gold": "For this review we searched widely for clinical trials of rTMS in people with ALS and found three studies, which involved 50 participants in total. All three compared rTMS with sham (inactive) rTMS. None of the three studies reported on disability or limitation in activity as assessed by a specific ALS scale (ALSFRS-R) at six months follow-up, which was what we chose as our primary measure of the effectiveness of rTMS. Other outcome measures were only available from 12 participants in one poor quality trial, in which there was no difference between rTMS and sham rTMS in ALSFRS-R or a test of muscle strength at 12 months\u2019 follow-up. None of the studies reported any adverse effects with rTMS. The trials in this review had small numbers of participants and some problems of design, so larger, well-designed trials should be considered, to determine the efficacy and safety of rTMS in ALS. However, the potential benefit should be balanced against the impact of taking part in trials for people with ALS."
    },
    {
        "index": "cochrane-simplification-test-286",
        "sentence": "We included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months. No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial. There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12). Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.",
        "gold": "Three new studies were included in this update of the review published in 2005 making a total of 10 randomised controlled trials with a total of 1049 participants. All studies involved different comparisons, none had a placebo group. Different doses and formulations of corticosteroids plus azathioprine showed no significant differences in disease control, although azathioprine reduced the amount of prednisone required for disease control. There were no significant differences in healing or disease-free intervals in participants taking azathioprine compared with mycophenolate mofetil, or in disease response comparing tetracycline plus nicotinamide with prednisolone. One small study using Chinese traditional medicine, 'Jingui Shenqi Pill' (JSP), plus prednisone did not show any benefit in favour of adding this traditional Chinese herbal remedy. Most of the deaths were in participants taking high doses of oral corticosteroids. The review of trials concluded that lower doses of oral steroids and strong steroid creams seem safe and effective. However, the use of steroid creams in extensive disease may be limited by side-effects and the practicality of applying creams to large areas of the skin. Milder regimens of topical steroids are safe and effective in moderate BP. More research is needed on treatments for BP, in particular, the effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and the treatment with tetracyclines and nicotinamide."
    },
    {
        "index": "cochrane-simplification-test-287",
        "sentence": "Seventy-five randomised trials, involving 7957 participants with irritable bowel syndrome, met the inclusion criteria. The methodological quality of three double-blind, placebo-controlled trials was high, but the quality of remaining trials was generally low. Seventy-one different herbal medicines were tested in the included trials, in which herbal medicines were compared with placebo or conventional pharmacologic therapy. Herbal medicines were also combined with conventional therapy and compared to conventional therapy alone. Compared with placebo, a Standard Chinese herbal formula, individualised Chinese herbal medicine, STW 5 and STW 5-II, Tibetan herbal medicine Padma Lax, traditional Chinese formula Tongxie Yaofang, and Ayurvedic preparation showed significantly improvement of global symptoms. Compared with conventional therapy in 65 trials testing 51 different herbal medicines, 22 herbal medicines demonstrated a statistically significant benefit for symptom improvement, and 29 herbal medicines were not significantly different than conventional therapy. In nine trials that evaluated herbal medicine combined with conventional therapy, six tested herbal preparations showed additional benefit from the combination therapy compared with conventional monotherapy. No serious adverse events from the herbal medicines were reported. Some herbal medicines may improve the symptoms of irritable bowel syndrome. However, positive findings from less rigorous trials should be interpreted with caution due to inadequate methodology, small sample sizes, and lack of confirming data. Some herbal medicines deserve further examination in high-quality trials.",
        "gold": "Traditional Chinese herbal medicine is a common practice in the East, and some clinical trials show a benefit of herbal medicines for symptomatic treatment of this condition. This systematic review identified and included 75 randomised clinical trials evaluating the effects of various herbal preparations (including single herbs or mixtures of different herbs) for treating people with irritable bowel syndrome. The review shows that some herbal medicines improve global symptoms such as abdominal pain, diarrhoea and/or constipation. However, the methodological quality of the majority of clinical trials evaluating these herbs was generally poor. There is evidence indicating that small, poor quality trials with positive findings are more likely to be associated with exaggerated effects. Although the included trials did not report serious adverse effects from using herbal medicines more research is needed to determine the safety of herbal medicines. In conclusion, herbal medicines might be promising for the treatment of irritable bowel syndrome. However, it is premature to recommend herbal medicines for routine use in irritable bowel syndrome. Testing the herbs in larger, well-designed trials is needed in order to establish sound evidence for their use."
    },
    {
        "index": "cochrane-simplification-test-288",
        "sentence": "We found 22 trials that evaluated pericoital use of LNG and other hormonal drugs on a regular basis to prevent pregnancy. The studies included a total of 12,400 participants, and were conducted in Europe, Asia, and the Americas. The drugs and doses evaluated included levonorgestrel (LNG) 0.75 mg (11 studies), LNG in doses other than 0.75 mg (4 trials), and hormones other than LNG (7 trials). Outcomes included pregnancy rates, discontinuation, side effects, and acceptability. Pericoital levonorgestrel was reasonably efficacious and safe. The pooled Pearl Index for the 0.75 mg dose of LNG was 5.4 per 100 woman-years (95% CI 4.1 to 7.0). The pooled Pearl Index for all doses of LNG was 5.0 per 100 woman-years (95% CI 4.4 to 5.6). Other hormonal drugs appeared promising but most of them were not studied extensively. Menstrual irregularities were the most common side effects reported. However, the studies provided no consistent evidence of a relationship between bleeding abnormalities and either frequency of pill intake or total dose of the drug. Non-menstrual side effects were reportedly mild and not tabulated in most studies. Most women liked the pericoital method in spite of frequent menstrual irregularities. The studies of pericoital LNG regimens provided promising results but many had serious methodological issues.\u00a0Most reports were decades old and provided limited information. However, we considered the evidence to be moderate quality because of the large number of participants from diverse populations, the low pregnancy rates, and the consistent results across studies. Rigorous research is still needed to confirm the efficacy and safety of pericoital use of LNG as a primary means of contraception among women with infrequent intercourse. If the method is shown to be efficacious, safe and acceptable, the results may warrant revision of the current World Health Organization recommendations and marketing strategies.",
        "gold": "We ran computer searches until 1 September 2014 to find relevant studies in any language. For the initial review, we also wrote to researchers to find other trials. We assessed the quality of the research methods in the studies. We used the Pearl Index to estimate the effect. The Pearl Index is the number of pregnancies for every 100 years of pill use. We found 22 studies from the past 40 years. They included a total of 12,400 women in Europe, Asia, and the Americas. Fifteen trials studied different doses of the hormone levonorgestrel and seven looked at other hormones. These studies showed that using some hormones right before or after sex did prevent pregnancy. Levonorgestrel seemed to work well, and was safe and accepted by thousands of women in several large trials. The most common side effects were menstrual bleeding problems. However, such bleeding issues were not always related to how often women took the pills or the total dose of the drug. Most studies were old and many reports were not complete. However, the data had moderate quality because of the many women in these studies, the low pregnancy rates, and the consistent results. We do not know for sure whether using levonorgestrel repeatedly around the time of sex is a good and safe method of birth control. More high-quality research is needed to answer the question."
    },
    {
        "index": "cochrane-simplification-test-289",
        "sentence": "Fourteen new studies were added in this update resulting in a total of 15 studies reporting data from 561 randomised patients. The studies were conducted in Europe, India, China, South Korea and the USA. The age range of patients was commonly restricted to adolescents or young adults, however the participants of two studies were from a much wider age range (12 to 54 years). The distribution of males and females was similar in eight of the studies, with a predominance of female patients in seven studies. Eight studies were assessed to be at high overall risk of bias; six studies at unclear risk of bias; one study at low risk of bias. Ten studies with 407 randomised and 390 analysed patients compared surgical anchorage with conventional anchorage for the primary outcome of mesiodistal movement of upper first molars. We carried out a random-effects model meta-analysis for the seven studies that fully reported this outcome. There was strong evidence of an effect of surgical anchorage on this outcome. Compared with conventional anchorage, surgical anchorage was more effective in the reinforcement of anchorage by 1.68 mm (95% confidence interval (CI) -2.27 mm to -1.09 mm; seven studies, 308 participants analysed) with moderate quality of evidence (one study at high overall risk of bias, five studies at unclear risk of bias, one study at low risk of bias). This result should be interpreted with some caution, however, as there was a substantial degree of heterogeneity for this comparison. There was no evidence of a difference in overall duration of treatment between surgical and conventional anchorage (-0.15 years; 95% CI -0.37 years to 0.07 years; three studies, 111 analysed patients) with low quality of evidence (one study at high overall risk of bias and two studies at unclear risk of bias). Information on patient-reported outcomes such as pain and acceptability was limited and inconclusive. When direct comparisons were made between two types of surgical anchorage, there was a lack of evidence to suggest that any one technique was better than another. No included studies reported adverse effects. There is moderate quality evidence that reinforcement of anchorage is more effective with surgical anchorage than conventional anchorage, and that results from mini-screw implants are particularly promising. While surgical anchorage is not associated with the inherent risks and compliance issues related to extraoral headgear, none of the included studies reported on harms of surgical or conventional anchorage.",
        "gold": "The evidence on which this review is based was correct as of 28 October 2013. This is an update to an existing review, which included one study. Fifteen studies were included in this review involving data from 561 participants. The studies were conducted in Europe, India, China, South Korea and the USA. Most took place in university settings or training hospitals and one in a specialist orthodontic practice. Most studies contained a similar number of males and females, however there were more females than males in five studies and only females in two. The age range varied from adolescents and young adults to adults up to the age of 54 years. All participants in the studies needed a course of orthodontic treatment with additional anchorage control. None of the studies reported adverse effects. When surgically implanted anchorage devices were compared to conventional anchorage devices, they were better in providing stabilisation for preventing unwanted movement in teeth during orthodontic treatment. There was limited information on patient-reported outcomes such as pain and how acceptable the devices were found to be. No information was reported on adverse events. The quality of the evidence for the important outcomes in this review ranged from moderate to low quality. The main shortcomings of all of the studies were related to issues with their design and the way they were carried out, with insufficient and low quality reporting of the study methods and outcomes."
    },
    {
        "index": "cochrane-simplification-test-290",
        "sentence": "We included 50 studies (45,285 participants): 47 studies (39,820 participants) compared statins with placebo or no treatment and three studies (5547 participants) compared two different statin regimens in adults with CKD who were not yet on dialysis. We were able to meta-analyse 38 studies (37,274 participants). The risk of bias in the included studies was high. Seven studies comparing statins with placebo or no treatment had lower risk of bias overall; and were conducted according to published protocols, outcomes were adjudicated by a committee, specified outcomes were reported, and analyses were conducted using intention-to-treat methods. In placebo or no treatment controlled studies, adverse events were reported in 32 studies (68%) and systematically evaluated in 16 studies (34%). Compared with placebo, statin therapy consistently prevented major cardiovascular events (13 studies, 36,033 participants; RR 0.72, 95% CI 0.66 to 0.79), all-cause mortality (10 studies, 28,276 participants; RR 0.79, 95% CI 0.69 to 0.91), cardiovascular death (7 studies, 19,059 participants; RR 0.77, 95% CI 0.69 to 0.87) and MI (8 studies, 9018 participants; RR 0.55, 95% CI 0.42 to 0.72). Statins had uncertain effects on stroke (5 studies, 8658 participants; RR 0.62, 95% CI 0.35 to 1.12). Potential harms from statin therapy were limited by lack of systematic reporting and were uncertain in analyses that had few events: elevated creatine kinase (7 studies, 4514 participants; RR 0.84, 95% CI 0.20 to 3.48), liver function abnormalities (7 studies, RR 0.76, 95% CI 0.39 to 1.50), withdrawal due to adverse events (13 studies, 4219 participants; RR 1.16, 95% CI 0.84 to 1.60), and cancer (2 studies, 5581 participants; RR 1.03, 95% CI 0.82 to 130). Statins had uncertain effects on progression of CKD. Data for relative effects of intensive cholesterol lowering in people with early stages of kidney disease were sparse. Statins clearly reduced risks of death, major cardiovascular events, and MI in people with CKD who did not have CVD at baseline (primary prevention). Statins consistently lower death and major cardiovascular events by 20% in people with CKD not requiring dialysis. Statin-related effects on stroke and kidney function were found to be uncertain and adverse effects of treatment are incompletely understood. Statins have an important role in primary prevention of cardiovascular events and mortality in people who have CKD.",
        "gold": "We looked at 50 studies published before June 2012 concerning statin treatment in over 45,000 people with CKD who did not need dialysis treatment. We found that statins reduced the risk of death and major heart-related events by 20%. Statin treatment was also found to be effective in reducing cardiac disease and death in people who have CKD but not heart disease. In these people, statin treatment reduced risks of heart attack by half. Statins have some potential harmful effects on liver and muscle function, and some cancers. We found that these issues were not analysed well in the studies we evaluated, and these effects are not well understood. Although use of statins did not clearly reduce risks of kidney disease progression, they can be recommended to reduce risks of death and heart-related events in people with early stages of kidney disease. However, the potential side-effects are uncertain, and need further study."
    },
    {
        "index": "cochrane-simplification-test-291",
        "sentence": "We identified 24,704 citations from our database search. Nine trials with 379 participants fulfilled our inclusion criteria. Participants had cerebral palsy (CP) in five of the studies and osteogenesis imperfecta (OI) in the other four. Participants across the trials ranged in age from 2 to 19 years. All studies, apart from one cross-over trial, were parallel designed RCTs. Three of the trials on CP evaluated intrathecal baclofen (ITB) and two botulinum toxin A (BoNT-A). All of the OI trials evaluated the use of bisphosphonates (two alendronate and one pamidronate). No trials were identified that evaluated a commonly used analgesic in this patient group. Pain was a secondary outcome in five of the eight identified studies. Overall the quality of the trials was mixed. Only one study involved over 100 participants. For the two ITB studies for pain in CP, in the same study population but assessed at different time points in their disease, both found an effect on pain favouring the intervention compared to the control group (standard care or placebo) (mean difference (MD) 4.20, 95% confidence interval (CI) 2.15 to 6.25; MD 26.60, 95% CI 2.61 to 50.59, respectively). In these studies most of the adverse events related to the procedure or device for administration rather than the drug, such as swelling at the pump site. In one trial there were also eight serious adverse effects; these included difficulty swallowing and an epileptic seizure. The trial did not state if these occurred in the intervention group. At follow-up in both BoNT-A trials there was no evidence of a difference in pain between the trial arms among CP participants. The adverse events in the BoNT-A trials mostly involved those who received the intervention drug and involved seizures. Gastrointestinal problems were the most frequent adverse event in those who received alendronate. The trial investigating pamidronate found no evidence of a difference in pain compared to the control group. No adverse events were reported in this trial. Published, controlled evidence on the pharmacological interventions for pain in CYP with LLCs is limited. The evidence that is currently available evaluated pain largely as a secondary outcome and the drugs used were all adjuvants and not always commonly used in general paediatric palliative care for pain. Based on current data this systematic review is unable to determine the effects of pharmacological interventions for pain for CYP with LLCs. Future trials with larger populations should examine the effects of the drugs commonly used as analgesics; with the rising prevalence of many LLCs this becomes more necessary.",
        "gold": "Overall, these trials did not find clear evidence of a benefit of the drugs tested in the treatment of pain. This was apart from the two on cerebral palsy where pain relief occurred with the use of baclofen delivered via a catheter into the spinal cord. However the procedure to deliver this medication resulted in most side effect reported in these trials; this was swelling at the site of the catheter, and in one study it reported that this occurred in around half of the children (8/17). Five children also leaked spinal fluid from the catheter resulting in headache and nausea and, for two children, a prolonged hospital stay. The trials were limited by the quality of their methods and most did not set out to measure the benefit of the drug in reducing pain as a main focus. In conclusion, the evidence on pain treatment in children and young people with life-limiting health conditions is very limited, and only evaluated in participants with certain diseases and not for drug treatments primarily used to treat pain. The trials that were identified evaluated the drugs in small samples of children. There remains a need for more research to help guide doctors in their decisions on how to treat pain in these children and young people."
    },
    {
        "index": "cochrane-simplification-test-292",
        "sentence": "Seven trials involving a total of 1697 participants were found and six were included in the quantitative analyses. No data were available from the seventh trial. Three trials involving 1243 patients were included in analyses of efficacy outcomes, and four trials involving 1034 patients were included in analyses of safety and tolerability outcomes. We judged five trials to be at high risk of bias due to selective outcome reporting and three to be at high risk of attrition bias. There was low quality evidence favouring latrepirdine on the Clinician's Interview - Based Impression of Change Plus Caregiver Input after 26 weeks (CIBIC-Plus) (MD -0.60, 95% CI -0.89 to -0.31, 1 study, P < 0.001). Due to imprecision in the results, it was not possible to determine whether latrepirdine had any effect on cognition measured with the Alzheimer\u2019s Disease Assessment Scale cognitive subscale (ADAS-Cog) (MD -1.49, 95% CI -3.47 to 0.49, 3 studies, P = 0.14) or the Mini-Mental State Examination (MMSE) (MD 0.59, 95% CI -0.94 to 2.11, 3 studies, P = 0.45), or on function measured with the Alzheimer\u2019s Disease Co-operative Study - Activities of Daily Living scale (ADCS-ADL) (MD 1.00, 95% CI -1.15 to 3.15, 3 studies, P = 0.36) at study endpoint (26 or 52 weeks). We considered the evidence provided on these outcomes to be of overall low quality. However, there was some high quality evidence showing a very small benefit of latrepirdine on the Neuropsychiatric Inventory (NPI) (MD -1.77, 95% CI -3.09 to -0.45, 3 studies, P = 0.009) at study endpoint (26 or 52 weeks). Additionally, moderate quality evidence suggested that latrepirdine and placebo were comparable in adverse events (RR 1.03, 95% CI 0.93 to 1.14, P = 0.51), serious adverse events (RR 0.86, 95% CI 0.55 to 1.35, P = 0.52), dropouts (RR 0.91, 95% CI 0.65 to 1.27, P = 0.57) and dropouts due to adverse events (RR 0.98, 95% CI 0.57 to 1.67, P = 0.93). Our meta-analysis is limited by the small number of studies, imprecision, inconsistencies between studies and likelihood of bias. Nevertheless, the evidence to date suggests that while not associated with an increased risk of adverse events compared with placebo, there is no effect of latrepirdine on cognition and function in mild-to-moderate AD patients, though there appears to be a modest benefit for behaviour. Further studies should investigate the potential benefit of latrepirdine on neuropsychiatric symptoms in AD.",
        "gold": "Clinical studies have had conflicting findings, so we conducted a systematic review and pooled all the available data to assess the effects of latrepirdine. We looked for studies to help us answer this question by conducting a literature search in June 2014. We combined data from seven studies with a total of 1697 patients with AD. We were unable to conclude whether latrepirdine has any beneficial effect on cognition and function in people with AD due to variations in the results between studies and because the effects we estimated were too imprecise. However, the evidence suggests that latrepirdine may have a positive effect in treating behavioural symptoms, and that it is not associated with adverse effects in people with AD. Although seven studies have been done, data from only six studies were available and most of the studies were not fully reported. We contacted the investigators for additional data but received no response."
    },
    {
        "index": "cochrane-simplification-test-293",
        "sentence": "We included seven trials, involving 735 participants, in this review. We analysed the effects of RIC on preventing and treating ischaemic stroke respectively. We evaluated risk of bias and judged it to be low for generation of allocation sequence in six studies and unclear in one study; unclear for allocation concealment in four studies and low in three studies; high for incomplete outcome data (attrition bias) in five studies and low in two studies; high for blinding in three studies and low in four studies; low for selective reporting; and high for other sources of bias in six studies and low in one study. We included three trials (involving 371 participants) in the analysis of the effects of RIC on ischaemic stroke prevention. In people with symptomatic intracerebral artery stenosis, recurrent stroke was significantly reduced by RIC (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.12 to 0.83; 2 trials, 182 participants, low-quality evidence). In people with carotid stenosis undergoing carotid stenting, there was no significant difference in the incidence of ischaemic stroke between participants treated with RIC and non-RIC (RR 0.22, 95% CI 0.01 to 4.03; 1 trial, 189 participants, low-quality evidence); however the stroke severity (assessed by infarct volume) was significantly lower in participants treated with RIC (mean difference (MD) -0.17 mL, 95% CI -0.23 to -0.11; 1 trial, 189 participants, low-quality evidence). Adverse events associated with RIC were significantly higher in participants treated with RIC (RR 10.91; 95% CI 2.01 to 59.28; 3 trials, 371 participants, low-quality evidence), but no severe adverse event was attributable to RIC treatment. No participants experienced death or cardiovascular events during the period of the studies; and no trial reported haemorrhagic stroke or improvement in neurological, phycological or cognitive impairment. We included four trials (involving 364 participants) in the analysis of the effects of RIC on ischaemic stroke treatment. In acute ischaemic stroke, for people receiving intravenous thrombolysis, the rate of death or dependency was significantly increased by RIC treatment compared with non-RIC treatment (RR 2.34; 95% 1.19 to 4.61; 1 trial, 285 participants, low-quality evidence). In people with acute ischaemic stroke, there was no significant difference between RIC and non-RIC for reducing stroke severity as assessed by the National Institutes of Health Stroke Scale score and the final infarct volume (standardised mean difference (SMD) -0.24 mL, 95% CI -1.02 to 0.54; 2 trials, 175 participants, very low quality evidence). There was no significant difference between RIC and non-RIC for improving the psychological impairment (SMD -0.37 points, 95% CI -1.15 to 0.41; 1 trial, 26 participants, very low quality evidence) and the cognitive impairment (SMD -0.26 points; 95% CI -0.72 to 0.21; 3 trials, 79 participants, low-quality evidence) in people with acute ischaemic stroke and cerebral small vessel disease. No trial reported ischaemic stroke, recurrent ischaemic stroke, improvement in neurological impairment, hemorrhagic stroke, cardiovascular events, and RIC associated adverse events. We found low-quality evidence that RIC may reduce the risk of recurrent stroke in participants with intracerebral artery stenosis and reduce stroke severity in participants undergoing carotid stenting, but it may increase death or dependence in participants with acute ischaemic stroke who are undergoing intravenous thrombolysis. However, there is considerable uncertainty about these conclusions because of the small number of studies and low quality of the evidence.",
        "gold": "This review included seven studies (specifically randomised controlled trials), involving 735 people. The studies compared RIC with sham RIC or medical management in people with ischaemic stroke or at risk of ischaemic stroke. Three trials (involving 371 people) were eligible for our analysis of RIC for preventing ischaemic stroke, and another four trials (involving 364 people) were eligible for our analysis of RIC for treating ischaemic stroke. The included trials were carried out in China, Denmark, and the UK. The results of this review are current up to January 2018. In people with narrowing of arteries in the brain, RIC may reduce the risk of recurrent stroke. In people being treated with stenting (the insertion of a metal or plastic tube) for narrowed arteries in the neck, RIC may reduce the size of new brain injuries caused by reduced blood flow. However, its effect on clinical outcomes (stroke and death) was unclear. Adverse events were significantly more common in the RIC group but were not reported to be severe. Among people with acute ischaemic stroke (where it had only been several hours from symptom onset) who received clot-dissolving medicines, we found that RIC may increase the risk of death or dependency (needing help from others). We found no significant differences in the size of the final stroke. In people with acute ischaemic stroke and chronic blood vessel disease of the brain, RIC did not affect measures of nerve function, mood, or thinking ability. There is low-quality evidence which suggests that RIC may help prevent recurrent stroke in people with narrowed arteries in the brain, and may increase death or dependency in people with acute ischaemic stroke who received clot dissolving medication. The evidence is less clear for reducing the volume of the stroke (size of brain lesion caused by low blood flow). Further research is likely to have an important impact on our confidence in these findings."
    },
    {
        "index": "cochrane-simplification-test-294",
        "sentence": "We included six RCTs, involving 204 preterm infants. Low-quality evidence showed that protein supplementation of human milk increased in-hospital rates of growth in weight (MD 3.82 g/kg/day, 95% CI 2.94 to 4.7; five RCTs, 101 infants; I\u00b2 = 73%), length (MD 0.12 cm/wk, 95% CI 0.07 to 0.17; four RCTs, 68 infants; I\u00b2 = 89%), and head circumference (MD 0.06 cm/wk, 95% CI 0.01 to 0.12; four RCTs, 68 infants; I\u00b2 = 84%). There was no evidence of a clear difference in rate of growth of skin fold thickness between the supplemented and unsupplemented groups (triceps MD 0.06 mm/wk, 95% CI \u20130.09 to 0.21; one RCT, 20 infants; or subscapular MD 0.00 mm/wk, 95% CI \u20130.17 to 0.17; one RCT, 20 infants). Protein supplementation led to longer hospital stays (MD 18.5 days, 95% CI 4.39 to 32.61; one RCT, 20 infants; very low-quality evidence), and higher blood urea nitrogen concentrations compared to the unsupplemented group (MD 0.95 mmol/L, 95% CI 0.81 to 1.09; four RCTs, 81 infants; I\u00b2 = 56%). Very low-quality evidence did not show that protein supplementation clearly increased the risk of feeding intolerance (RR 2.70, 95% CI 0.13 to 58.24; one RCT, 17 infants), or necrotizing enterocolitis (RR 1.11, 95% CI 0.07 to 17.12; one RCT, 76 infants), or clearly altered serum albumin concentrations (MD 2.5 g/L, 95% CI \u20135.66 to 10.66; one RCT, 11 infants), compared with the unsupplemented groups. No data were available about the effects of protein supplementation on long-term growth, body mass index, body composition, neurodevelopmental, or cardio-metabolic outcomes. Low-quality evidence showed that protein supplementation of human milk, fed to preterm infants, increased short-term growth. However, the small sample sizes, low precision, and very low-quality evidence regarding duration of hospital stay, feeding intolerance, and necrotising enterocolitis precluded any conclusions about these outcomes. There were no data on outcomes after hospital discharge. Our findings may not be generalisable to low-resource settings, as none of the included studies were conducted in these settings. Since protein supplementation of human milk is now usually done as a component of multi-nutrient fortifiers, future studies should compare different amounts of protein in multi-component fortifiers, and be designed to determine the effects on duration of hospital stay and safety, as well as on long-term growth, body composition, cardio-metabolic, and neurodevelopmental outcomes.",
        "gold": "We found six randomised trials (trials in which each infant had an equal chance of being chosen to receive either treatment), involving 204 preterm infants. The search is up to date to February 2018. Low-quality evidence showed that the addition of extra protein to breast milk increased short-term rates of weight gain (five trials), length gain (four trials), and head growth (four trials). Low-quality evidence from one trial did not show a clear difference in the rate of growth of skin fold thickness (measure of fat under the skin) between the supplemented and unsupplemented groups. Very low-quality evidence from one trial reported that infants who received additional protein stayed in hospital longer, while very low-quality evidence from four trials observed higher blood urea nitrogen concentrations (measure of kidney function and protein breakdown) in these infants, compared to those who received no additional protein. Very low-quality evidence from one trial suggested that adding extra protein to expressed breast milk did not clearly increase the risk of necrotising enterocolitis (inflammation of the intestine) or feeding intolerance, or clearly alter serum albumin concentrations (a measure of blood protein levels). No data were available on the effects of adding extra protein to human milk on long-term growth, body fat, obesity, high blood sugar, or brain development. Adding extra protein to human milk for preterm infants may increase short-term growth. However, its effect on length of hospital stay, feeding intolerance, and necrotizing enterocolitis is uncertain, due to data limitations and very low-quality evidence. There were no data about effects on later health and development, or effects in low resource settings. Since protein supplementation of human milk is now usually done as a component of multi-nutrient fortifiers, future studies should compare different amounts of protein in multi-component fortifiers, and be designed to determine the effects on length of hospital stay, safety, long-term growth, body fat, obesity, high blood sugar, and brain development."
    },
    {
        "index": "cochrane-simplification-test-295",
        "sentence": "The review includes 45 studies: 14 RCTs and 31 ITS studies. Almost all the included studies (44/45) compared the effectiveness of PEM to no intervention. One single study compared paper-based PEM to the same document delivered on CD-ROM. Based on seven RCTs and 54 outcomes, the median absolute risk difference in categorical practice outcomes was 0.02 when PEMs were compared to no intervention (range from 0 to +0.11). Based on three RCTs and eight outcomes, the median improvement in standardised mean difference for continuous profession practice outcomes was 0.13 when PEMs were compared to no intervention (range from -0.16 to +0.36). Only two RCTs and two ITS studies reported patient outcomes. In addition, we re-analysed 54 outcomes from 25 ITS studies, using time series regression and observed statistically significant improvement in level or in slope in 27 outcomes. From the ITS studies, we calculated improvements in professional practice outcomes across studies after PEM dissemination (standardised median change in level = 1.69). From the data gathered, we could not comment on which PEM characteristic influenced their effectiveness. The results of this review suggest that when used alone and compared to no intervention, PEMs may have a small beneficial effect on professional practice outcomes. There is insufficient information to reliably estimate the effect of PEMs on patient outcomes, and clinical significance of the observed effect sizes is not known. The effectiveness of PEMs compared to other interventions, or of PEMs as part of a multifaceted intervention, is uncertain.",
        "gold": "Medical journals and clinical practice guidelines are common channels to distribute scientific information to healthcare providers, as they allow a wide distribution at relatively low costs. Delivery of printed educational materials is meant to improve healthcare professionals' awareness, knowledge, attitudes, and skills, and ultimately improve professional practice and patients' health outcomes. Results of this review suggest that printed educational materials slightly improve healthcare professional practice compared to no intervention, but a lack of results prevent any conclusion on their impact on patient outcomes."
    },
    {
        "index": "cochrane-simplification-test-296",
        "sentence": "A total of 5271 references were screened and of these 23 RCTs met the inclusion criteria. Most were conducted in the USA and in health-care clinics (e.g. family planning). The majority of interventions provided information about STIs and taught safer sex skills (e.g. communication), occasionally supplemented with provision of resources (e.g. free sexual health services). They were heterogeneous in duration, contact time, provider, behavioural aims and outcomes. A variety of STIs were addressed including HIV and chlamydia. None of the trials explicitly mentioned HPV or cervical cancer prevention. Statistically significant effects for behavioural outcomes (e.g. increasing condom use) were common, though not universal and varied according to the type of outcome. There were no statistically significant effects of abstaining from or reducing sexual activity. There were few statistically significant effects on biological (STI) outcomes. Considerable uncertainty exists in the risk of bias due to incomplete or ambiguous reporting. Behavioural interventions for young women which aim to promote sexual behaviours protective of STI transmission can be effective, primarily at encouraging condom use. Future evaluations should include a greater focus on HPV and its link to cervical cancer, with long-term follow-up to assess impact on behaviour change, rates of HPV infection and progression to cervical cancer. Studies should use an RCT design where possible with integral process evaluation and cost-effectiveness analysis where appropriate. Given the predominance of USA studies in this systematic review evaluations conducted in other countries would be particularly useful.",
        "gold": "Searches identified 5271 bibliographic records. Screening the records independently by two review authors identified 23 relevant randomised controlled trials (RCTs). The trials were mostly conducted in the USA (21 trials) and in health-care (e.g. family planning) clinics (14 trials), with only four in educational settings. Trial participants had mixed socio-economic and demographic characteristics and most were sexually experienced. The interventions mostly provided information about STIs and taught safer sex skills (e.g. communication with partners), occasionally supplemented with provision of resources (e.g. free sexual health services). Interventions varied considerably in duration, contact time, provider, behavioural aims and outcomes. A variety of STIs were addressed including HIV and chlamydia, but not explicitly HPV. The most common behavioural outcome (measured in 19 trials) was condom use for vaginal intercourse. Sexual partners, sexual abstinence and STIs were reported in four, two and 12 trials respectively. In terms of statistically significant effects, some interventions improved condom-related behaviour and reduced the number of sexual partners, but none affected the frequency of sexual episodes. Effects of interventions on STIs were limited. None of the interventions appeared to be harmful. The methods used in the trials were not always well described making it difficult to tell whether their results may have been biased. In conclusion, although some behavioural interventions improve condom-related behaviour, trials have been predominantly in USA healthcare settings, did not specifically address HPV and were too different to enable a most effective type of intervention to be identified."
    },
    {
        "index": "cochrane-simplification-test-297",
        "sentence": "We included twenty studies with a total number of 2337 participants in this review. Nineteen studies compared brief psychoeducation with routine care or conventional delivery of information. One study compared brief psychoeducation with cognitive behavior therapy. Participants receiving brief psychoeducation were less likely to be non-compliant with medication than those receiving routine care in the short term (n = 448, 3 RCTs, RR 0.63 CI 0.41 to 0.96, moderate quality evidence) and medium term (n = 118, 1 RCT, RR 0.17 CI 0.05 to 0.54, low quality evidence). Compliance with follow-up was similar between the two groups in the short term (n = 30, 1 RCT, RR 1.00, CI 0.24 to 4.18), medium term (n = 322, 4 RCTs, RR 0.74 CI 0.50 to 1.09) and long term (n = 386, 2 RCTs, RR 1.19, CI 0.83 to 1.72). Relapse rates were significantly lower amongst participants receiving brief psychoeducation than those receiving routine care in the medium term (n = 406, RR 0.70 CI 0.52 to 0.93, moderate quality evidence), but not in the long term. Data from a few individual studies supported that brief psychoeducation: i) can improve the long-term global state (n = 59, 1 RCT, MD -6.70 CI -13.38 to -0.02, very low quality evidence); ii) promote improved mental state in short term (n = 60, 1 RCT, MD -2.70 CI -4.84 to -0.56,low quality evidence) and medium term; iii) can lower the incidence and severity of anxiety and depression. Social function such as rehabilitation status (n = 118, 1 RCT, MD -13.68 CI -14.85 to -12.51, low quality evidence) and social disability (n = 118, 1 RCT, MD -1.96 CI -2.09 to -1.83, low quality evidence) were also improved in the brief psychoeducation group. There was no difference found in quality of life as measured by GQOLI-74 in the short term (n = 62, 1 RCT, MD 0.63 CI -0.79 to 2.05, low quality evidence), nor the death rate in either groups (n = 154, 2 RCTs, RR 0.99, CI 0.15 to 6.65, low quality evidence). Based on mainly low to very low quality evidence from a limited number of studies, brief psychoeducation of any form appears to reduce relapse in the medium term, and promote medication compliance in the short term. A brief psychoeducational approach could potentially be effective, but further large, high-quality studies are needed to either confirm or refute the use of this approach.",
        "gold": ". The review authors searched for randomised trials in 2013 and found 20 relevant studies with 2337 participants. Half of the studies were carried out in China. These trials randomised people to receive either brief psychoeducation sessions (these ranged from one-day psychoeducation to eight sessions of psychoeducation over a period of one year) or routine care. Based on information from a limited number of studies, brief psychoeducation does seem to reduce relapse and encourage people to take their medication. Those receiving brief psychoeducation also have more favourable results for mental state and social functioning. Although initial results are encouraging, most information and data for the main outcomes of interest, were rated as low or very low quality, and the number of trials providing useful data is small. Until further large, high-quality studies become available, the usefulness of brief psychoeducation remains debatable. Ben Gray, Senior Peer Researcher, McPin Foundation.http://mcpin.org/"
    },
    {
        "index": "cochrane-simplification-test-298",
        "sentence": "We included 11 studies comprising 9839 participants in our quantitative analysis. Most studies included people with moderate to severe COPD, without recent exacerbations. One pharmaceutical sponsored trial that included only people with recent exacerbations was the largest study and accounted for 37% of participants. All but one study were sponsored by pharmaceutical companies, thus we rated them as having a high risk of 'other bias'. The unsponsored study was at high risk of performance and detection bias, and possible selective reporting. Five studies recruited GOLD Category B participants, one study recruited Category D participants, two studies recruited Category A/B participants, and three studies recruited participants regardless of category. Follow-up ranged from 6 to 52 weeks. Compared to the LABA+ICS arm, the results for the pooled primary outcomes for the LAMA+LABA arm were as follows: exacerbations, OR 0.82 (95% CI 0.70 to 0.96, P = 0.01, I2 = 17%, low quality evidence); serious adverse events (SAE), OR 0.91 (95% CI 0.79 to 1.05, P = 0.18, I2 = 0, moderate quality evidence); St. George's Respiratory Questionnaire (SGRQ) total score change from the baseline, MD -1.22 (95% CI -2.52 to 0.07, P = 0.06, I2 = 71%, low quality evidence); and trough forced expiratory volume in one second (FEV1) change from the baseline, MD 0.08 L (95% CI 0.06 to 0.09, P < 0.0001, I2 = 50%, moderate quality evidence). Compared to the LABA+ICS arm, the results for the pooled secondary outcomes for the LAMA+LABA arm were as follows: pneumonia, OR 0.57 (95% CI 0.42 to 0.79, P = 0.0006, I2 = 0%, low quality evidence); all-cause death, OR 1.01 (95% CI 0.61 to 1.67, P = 0.88, I2 = 0%, low quality evidence); and SGRQ total score change from the baseline of 4 points or greater (the minimal clinically important difference for the SGRQ is 4 points), OR 1.25 (95% CI 1.09 to 1.44, P = 0.002, I2 = 0%, moderate quality evidence). For the treatment of COPD, LAMA+LABA has fewer exacerbations, a larger improvement of FEV1, a lower risk of pneumonia, and more frequent improvement in quality of life as measured by an increase over 4 units or more of the SGRQ. These data were supported by low or moderate quality evidence generated from mainly participants with moderate to severe COPD in heterogeneous trials with an observation period of less than one year. Our findings support the recently updated GOLD guidance.",
        "gold": "We included 11 studies involving 9839 participants comparing the benefits and harms of LAMA+LABA and LABA+ICS for the treatment of people with COPD. Although risk of serious side effects and death were not affected by the choice of treatment, compared to LABA+ICS, LAMA+LABA was associated with a lower risk of flare-ups, fewer episodes of pneumonia, larger improvement in how well the lungs work, and improved quality of life. Since most of the analysed studies were sponsored by pharmaceutical companies, we had to interpret the results carefully. However, we judged the included studies to be generally conducted in an acceptable manner. These data were supported by low or moderate quality evidence from trials in people with mainly moderate to severe COPD who were studied for less than one year."
    },
    {
        "index": "cochrane-simplification-test-299",
        "sentence": "We included 3 RCTs with 91 children aged between 6 months and 4 years. Study duration was from 7 to 16 months; all studies were conducted in emergency departments in the USA (two studies) and Spain. Heliox was administered as a mixture of 70% heliox and 30% oxygen. Risk of bias was low in two studies and high in one study due to an open-label design. We added no new trials for this update. One study of 15 children with mild croup compared heliox with 30% humidified oxygen administered for 20 minutes. There may be no difference in croup score changes between groups at 20 minutes (mean difference (MD) -0.83, 95% confidence interval (CI) -2.36 to 0.70). The mean croup score at 20 minutes postintervention may not differ between groups (MD -0.57, 95% CI -1.46 to 0.32). There may be no difference between groups in mean respiratory rate (MD 6.40, 95% CI -1.38 to 14.18) and mean heart rate (MD 14.50, 95% CI -8.49 to 37.49) at 20 minutes. The evidence for all outcomes in this comparison was of low quality, downgraded for serious imprecision. All children were discharged, but information on hospitalisation, intubation, or re-presenting to emergency departments was not reported. In another study, 47 children with moderate croup received one dose of oral dexamethasone (0.3 mg/kg) with either heliox for 60 minutes or no treatment. Heliox may slightly improve croup scores at 60 minutes postintervention (MD -1.10, 95% CI -1.96 to -0.24), but there may be no difference between groups at 120 minutes (MD -0.70, 95% CI -4.86 to 3.46). Children treated with heliox may have lower mean Taussig croup scores at 60 minutes (MD -1.11, 95% CI -2.05 to -0.17) but not at 120 minutes (MD -0.71, 95% CI -1.72 to 0.30). Children treated with heliox may have lower mean respiratory rates at 60 minutes (MD -4.94, 95% CI -9.66 to -0.22), but there may be no difference at 120 minutes (MD -3.17, 95% CI -7.83 to 1.49). There may be no difference in hospitalisation rates between groups (OR 0.46, 95% CI 0.04 to 5.41). We assessed the evidence for all outcomes in this comparison as of low quality, downgraded due to imprecision and high risk of bias related to open-label design. Information on heart rate and intubation was not reported. In the third study, 29 children with moderate to severe croup received intramuscular dexamethasone (0.6 mg/kg) and either heliox with one to two doses of nebulised saline, or 100% oxygen with one to two doses of adrenaline for three hours. Heliox may slightly improve croup scores at 90 minutes postintervention, but may have little or no difference overall using repeated measures analysis. We assessed the evidence for all outcomes in this comparison as of low quality, downgraded due to high risk of bias related to inadequate reporting. Information on hospitalisation or re-presenting to the emergency department was not reported. The included studies did not report on adverse events, intensive care admissions, or parental anxiety. We could not pool the available data because each comparison included data from only one study. Due to very limited evidence, uncertainty remains about the effectiveness and safety of heliox. Heliox may not be more effective than 30% humidified oxygen for children with mild croup, but may be beneficial in the short term for children with moderate to severe croup treated with dexamethasone. The effect may be similar to 100% oxygen given with one or two doses of adrenaline. Adverse events were not reported, and it is unclear if these were monitored in the included studies. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in the treatment of children with moderate to severe croup.",
        "gold": "We did not include any new trials in this update. We included three randomised controlled trials (studies in which participants are allocated by chance to receive a treatment) involving a total of 91 children with croup aged from 6 months to 4 years. Studies ran for between 7 and 16 months; two were conducted in the USA and one in Spain. In one study children with mild croup received either heliox with 30% oxygen; in another study children with moderate croup received oral dexamethasone (a type of corticosteroid) and either heliox or no treatment; and in the third study children with moderate to severe croup received injected dexamethasone and either heliox or 100% oxygen with adrenaline. Heliox may be no more effective than 30% oxygen for children with mild croup; as effective as 100% oxygen given with one or two doses of adrenaline; and slightly more effective than no treatment for children with moderate to severe croup. None of the studies reported adverse events. The quality of the evidence was low as the trials included few children, and in one trial children, their families, and the physicians knew which treatment was given."
    },
    {
        "index": "cochrane-simplification-test-300",
        "sentence": "Eight studies set in primary (four), secondary (one) and tertiary care (accident and emergency = three) were included in the review. Overall, the risk of bias of studies was moderate with high risk of selection and verification bias the predominant flaws. Reporting of index and reference tests was poor. The prevalence of vertebral fracture in accident and emergency settings ranged from 6.5% to 11% and in primary care from 0.7% to 4.5%. There were 29 groups of index tests investigated however, only two featured in more than two studies. Descriptive analyses revealed that three red flags in primary care were potentially useful with meaningful positive likelihood ratios (LR+) but mostly imprecise estimates (significant trauma, older age, corticosteroid use; LR+ point estimate ranging 3.42 to 12.85, 3.69 to 9.39, 3.97 to 48.50 respectively). One red flag in tertiary care appeared informative (contusion/abrasion; LR+ 31.09, 95% CI 18.25 to 52.96). The results of combined tests appeared more informative than individual red flags with LR+ estimates generally greater in magnitude and precision. The available evidence does not support the use of many red flags to specifically screen for vertebral fracture in patients presenting for LBP. Based on evidence from single studies, few individual red flags appear informative as most have poor diagnostic accuracy as indicated by imprecise estimates of likelihood ratios. When combinations of red flags were used the performance appeared to improve. From the limited evidence, the findings give rise to a weak recommendation that a combination of a small subset of red flags may be useful to screen for vertebral fracture. It should also be noted that many red flags have high false positive rates; and if acted upon uncritically there would be consequences for the cost of management and outcomes of patients with LBP. Further research should focus on appropriate sets of red flags and adequate reporting of both index and reference tests.",
        "gold": "Eight studies including several thousand patients described 29 different questions and physical exam tests that have been used to look for spinal fractures.\u00a0 Most of the 29 were not accurate.\u00a0 The best four questions asked about use of steroids (which can cause weak bones), the patient\u2019s age (age above 74 increases the risk of fractures) and recent trauma such as a fall.\u00a0 Using a combination of the best questions appears to improve the accuracy.\u00a0 For example, women above age 74 are more likely to have a fracture when they come to the physician complaining of back pain.\u00a0 In the emergency room, the best indication of a spinal fracture was a bruise or scrape on the painful area of the back. Fractures are rare and generally do not require emergency treatment, even if red flags exist clinicians and patients can watch and wait.\u00a0 During the waiting period, patients should avoid treatments like exercise and manipulation that are not recommended for spinal fractures. The worst effects of low quality red flag screening are overtreatment and undertreatment.\u00a0 If the tests are not accurate, patients without a fracture may get an x-ray or CT scan that they don\u2019t need\u2014unnecessary exposure to x-rays, extra worry for the patient and extra cost.\u00a0 At the other extreme (and much less common), it might be possible to miss a real fracture, and cause the patient to have extra time without the best treatment. Most of the studies were of low or moderate quality, so more research is needed to identify the best combination of questions and examination methods."
    },
    {
        "index": "cochrane-simplification-test-301",
        "sentence": "Two randomised trials were identified.\u00a0One trial compared the outcomes of surgical urethral dilatation and optical urethrotomy in 210 adult men with urethral stricture disease.\u00a0No significant difference was found in the proportion of men being stricture free at three years or in the median time to recurrence.\u00a0The second trial compared the outcomes of urethrotomy and urethroplasty in 50 men with traumatic stricture of the posterior urethra following pelvic fracture injury. In the first six months, men were more likely to require further surgery in the urethrotomy group than in the primary urethroplasty group (RR 3.39, 95% CI 1.62 to 7.07). After two years, 16 of 25 (64%) men initially treated by urethrotomy required continued self-dilatation or further surgery for stricture recurrence compared to 6 of 25 (24%) men treated by primary urethroplasty. There were insufficient data to perform meta-analysis or to reliably determine effect size. There were insufficient data to determine which intervention is best for urethral stricture disease in terms of balancing efficacy, adverse effects and costs.\u00a0Well designed, adequately powered multi-centre trials are needed to answer relevant clinical questions regarding treatment of men with urethral strictures.",
        "gold": "The uncertainty as to which option is best prompted this review of the current evidence. We found very little good quality evidence and were unable to achieve all our objectives for this review. The results of a single study suggest that dilatation and urethrotomy offer equivalent outcomes, but they are associated with a high rate of recurrence of the stricture requiring repeated procedures over a relatively short period of time. Preliminary data reported in abstract form suggested that urethroplasty was more effective than urethrotomy for the specific circumstance of urethral trauma following fracture of the pelvic bones. We found no data concerning well-being or the quality of life amongst men treated for urethral stricture disease. The main conclusion of the review is that the current lack of quality evidence means that further trials are needed to establish which intervention is most effective and most cost-effective for treatment of urethral stricture disease in men."
    },
    {
        "index": "cochrane-simplification-test-302",
        "sentence": "Six trials (including one trial testing two relevant protocols) met the inclusion criteria for a total of seven group comparisons. The four paediatric trials (two involving preschool children and two school-aged children) and two adult parallel-group trials, lasting 12 to 52 weeks, were of high methodological quality. A total of 1211 patients with confirmed, or suspected, persistent asthma contributed to the meta-analyses. There was no statistically significant group difference in the risk of patients experiencing one or more exacerbations requiring oral corticosteroids (1204 patients; RR 1.07; 95% CI 0.87 to 1.32; the large confidence interval translates into a risk of exacerbations in the intermittent ICS group varying between 17% and 25%, assuming a 19% risk with daily ICS). Age, severity of airway obstruction, step-up protocol used during exacerbations and trial duration did not significantly influence the primary efficacy outcome. No group difference was observed in the risk of patients with serious adverse health events (1055 patients; RR 0.82; 95% CI 0.33 to 2.03). Compared to the daily ICS group, the intermittent ICS group displayed a smaller improvement in change from baseline peak expiratory flow rate (PEFR) by 2.56% (95% CI -4.49% to -0.63%), fewer symptom-free days (standardised mean difference (SMD) -0.15 (95% CI -0.28 to -0.03), fewer asthma control days -9% (95% CI -14% to -4%), more use of rescue \u03b22-agonists by 0.12 puffs/day (95% CI 0 to 0.23) and a greater increase from baseline in exhaled nitric oxide of 16.80 parts per billion (95% CI 11.95 to 21.64). There was no significant group difference in forced expiratory volume in one second (FEV1), quality of life, airway hyper-reactivity, adverse effects, hospitalisations, emergency department visits or withdrawals. In paediatric trials, intermittent ICS (budesonide and beclomethasone) were associated with greater growth by 0.41 cm change from baseline (532 children; 95% CI 0.13 to 0.69) compared to daily treatment. In children and adults with persistent asthma and in preschool children suspected of persistent asthma, there was low quality evidence that intermittent and daily ICS strategies were similarly effective in the use of rescue oral corticosteroids and the rate of severe adverse health events. The strength of the evidence means that we cannot currently assume equivalence between the two options.. Daily ICS was superior to intermittent ICS in several indicators of lung function, airway inflammation, asthma control and reliever use. Both treatments appeared safe, but a modest growth suppression was associated with daily, compared to intermittent, inhaled budesonide and beclomethasone. Clinicians should carefully weigh the potential benefits and harm of each treatment option, taking into account the unknown long-term (> one year) impact of intermittent therapy on lung growth and lung function decline.",
        "gold": "This review of randomised controlled trials found no significant difference in the number of asthma attacks of moderate severity between people taking inhaled corticosteroids every day and those taking them 'as needed'. However, there was not enough information to conclude to that the two approaches were equivalent. We found that people taking inhaled corticosteroids everyday had slightly better asthma control with better lung function, less use of reliever medication and more symptom-free days than those taking inhaled corticosteroids intermittently. We also observed that compared to intermittent inhaled corticosteroids, children grew slightly less with daily inhaled budesonide and beclomethasone (inhaled corticosteroids are known to affect growth), underlying the importance of using the safest and lowest effective dose of inhaled corticosteroids. We did not observe any significant group difference in the rate of withdrawals or adverse effects. These results do not provide firm conclusions, although the improvement in asthma control, lung function and airway inflammation would provide slightly greater support for the use of inhaled corticosteroids every day as compared to taking them only when symptoms get worse. Physicians and patients are advised to weigh the risks and benefits of each treatment option carefully and monitor the response of individual patients to adjust therapy as needed."
    },
    {
        "index": "cochrane-simplification-test-303",
        "sentence": "We included 17 studies involving 1639 people with CKD. Three studies enrolled 341 people treated with dialysis, four studies enrolled 168 kidney transplant recipients, and 10 studies enrolled 1130 people with CKD stages 1 to 5. Eleven studies (900 people) evaluated dietary counselling with or without lifestyle advice and six evaluated dietary patterns (739 people), including one study (191 people) of a carbohydrate-restricted low-iron, polyphenol enriched diet, two studies (181 people) of increased fruit and vegetable intake, two studies (355 people) of a Mediterranean diet and one study (12 people) of a high protein/low carbohydrate diet. Risks of bias in the included studies were generally high or unclear, lowering confidence in the results. Participants were followed up for a median of 12 months (range 1 to 46.8 months). Studies were not designed to examine all-cause mortality or cardiovascular events. In very-low quality evidence, dietary interventions had uncertain effects on all-cause mortality or ESKD. In absolute terms, dietary interventions may prevent one person in every 3000 treated for one year avoiding ESKD, although the certainty in this effect was very low. Across all 17 studies, outcome data for cardiovascular events were sparse. Dietary interventions in low quality evidence were associated with a higher health-related quality of life (2 studies, 119 people: MD in SF-36 score 11.46, 95% CI 7.73 to 15.18; I2 = 0%). Adverse events were generally not reported. Dietary interventions lowered systolic blood pressure (3 studies, 167 people: MD -9.26 mm Hg, 95% CI -13.48 to -5.04; I2 = 80%) and diastolic blood pressure (2 studies, 95 people: MD -8.95, 95% CI -10.69 to -7.21; I2 = 0%) compared to a control diet. Dietary interventions were associated with a higher estimated glomerular filtration rate (eGFR) (5 studies, 219 people: SMD 1.08; 95% CI 0.26 to 1.97; I2 = 88%) and serum albumin levels (6 studies, 541 people: MD 0.16 g/dL, 95% CI 0.07 to 0.24; I2 = 26%). A Mediterranean diet lowered serum LDL cholesterol levels (1 study, 40 people: MD -1.00 mmol/L, 95% CI -1.56 to -0.44). Dietary interventions have uncertain effects on mortality, cardiovascular events and ESKD among people with CKD as these outcomes were rarely measured or reported. Dietary interventions may increase health-related quality of life, eGFR, and serum albumin, and lower blood pressure and serum cholesterol levels. Based on stakeholder prioritisation of dietary research in the setting of CKD and preliminary evidence of beneficial effects on risks factors for clinical outcomes, large-scale pragmatic RCTs to test the effects of dietary interventions on patient outcomes are required.",
        "gold": "We found 17 studies involving 1639 people who had chronic kidney disease that looked into whether diet changes or advice improved their health. Studies included men and women with mainly moderate or severe kidney disease. Diets involved increasing fruit and vegetable intake, increasing poultry and fish, higher nut and olive oil use, and some increases in cereals and legumes (e.g. beans), and less red meat, sugar, and salt. We looked particularly at three key outcomes: the risk of death, the risk of advanced kidney disease requiring dialysis, and quality of life. There were four studies involving people who have had a kidney transplant and three studies involving people treated with dialysis. After combining the available studies, it was uncertain whether making healthy diet changes prevented heart complications as most studies did not measure these. Diet changes may improve life quality. We did see that some risk factors for future disease, such as blood pressure and cholesterol, were lower following diet counselling or healthier eating. The quality of the included studies was often very low meaning we could not be sure that future studies would find similar results. We are very uncertain whether dietary changes improve well-being for people with kidney disease because the available research studies were not designed to learn about these. Diet changes may lower blood pressure and cholesterol, but the longer term impact of these effects on well-being is not proven. This means we still need large and good-quality research studies to help understand the impact of diet on the health of people with kidney disease."
    },
    {
        "index": "cochrane-simplification-test-304",
        "sentence": "Only one study (156 children aged between seven weeks and 24 months with signs and symptoms of bronchiolitis) met the eligibility criteria for inclusion. Participants were randomised into three groups: nebulised salbutamol, nebulised saline and mist in a tent. The results showed a significant decrease in respiratory distress symptom (RDS) score in the nebulised salbutamol group but no significant decrease in the RDS score in the mist in a tent or nebulised saline groups. The study did not report on adverse effects of the interventions. Steam inhalation (or cool mist therapy) is commonly used to treat acute bronchiolitis in resource-constrained settings. One study was eligible for inclusion and found that nebulised salbutamol was an effective intervention for young children with bronchiolitis but mist in a tent did not lead to a significant decrease in RDS score. Since only one study was analysed it would be misleading to conclude that mist therapy is ineffective in children with bronchiolitis. We conclude that there is insufficient evidence to inform practice regarding using steam inhalation or mist therapy for acute bronchiolitis in children up to three years old.",
        "gold": "Humidified air as steam inhalation or mist is thought to help the patient by lightening respiratory tract secretions and relieving the symptoms of respiratory distress. We searched and reviewed studies that used humidified air alone or in combination with drugs to relieve the symptoms of the infection in children less than three years of age. We found only one study (156 children) that met our criteria for analysis. The study compared nebulised salbutamol and mist in a tent (humidified air). The results showed that nebulised salbutamol was effective in relieving respiratory distress in acute bronchiolitis in young children while mist therapy was not effective. The study did not report on adverse effects for either intervention. Although the study was of high quality, some issues regarding patient allocation to the various treatment groups were not very satisfactory. There is currently not enough evidence to state that steam inhalation or mist is useful in young children with bronchiolitis. More well-designed trials of the effectiveness of humidified oxygen, mist therapy or steam inhalation compared with other treatments for acute bronchiolitis are needed."
    },
    {
        "index": "cochrane-simplification-test-305",
        "sentence": "We identified four studies (1154 participants, age range 50 to 90 years). All participants had a diagnosis of probable or possible AD according to standard criteria and most participants were established on a cholinesterase inhibitor. The primary outcome in all studies was change in Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) from baseline. When we pooled data, there was no significant benefit from statin (mean difference -0.26, 95% confidence interval (CI) -1.05 to 0.52, P value = 0.51). All studies provided change in Mini Mental State Examination (MMSE) from baseline. There was no significant benefit from statins in MMSE when we pooled the data (mean difference -0.32, 95% CI -0.71 to 0.06, P value = 0.10). Three studies reported treatment-related adverse effects. When we pooled data, there was no significant difference between statins and placebo (odds ratio 1.09, 95% CI 0.58 to 2.06, P value = 0.78). There was no significant difference in behaviour, global function or activities of daily living in the statin and placebo groups. We assessed risk of bias as low for all studies. We found no studies assessing role of statins in treatment of VaD. Analyses from the studies available, including two large randomised controlled trials, indicate that statins have no benefit on the primary outcome measures of ADAS-Cog or MMSE.",
        "gold": "Two independent authors searched scientific databases for studies in which a statin or a placebo (a pretend treatment) was given for at least six months. We included people with a probable or possible diagnosis of Alzheimer's disease according to standard clinical criteria. The findings were current to January 2014. We identified four studies involving 1154 participants (age range 50 to 90 years). The studies used standard tests to assess the severity of Alzheimer's disease. From these trials, including two large trials, we found no evidence that statins help in the treatment of cognitive decline in dementia. The quality of evidence is felt to be high as two large randomised controlled trials have been included along with two smaller ones."
    },
    {
        "index": "cochrane-simplification-test-306",
        "sentence": "Four studies involving 149 participants met inclusion criteria for this review. Two studies assessed the effect of night splinting in a total of 26 children and adults with Charcot-Marie-Tooth disease type 1A. There were no statistically or clinically significant differences between wearing a night splint and not wearing a night splint. One study assessed the efficacy of prednisone treatment in 103 boys with Duchenne muscular dystrophy. While a daily dose of prednisone at 0.75 mg/kg/day resulted in significant improvements in some strength and function parameters compared with placebo, there was no significant difference in ankle range of motion between groups. Increasing the prednisone dose to 1.5 mg/kg/day had no significant effect on ankle range of motion. One study evaluated early surgery in 20 young boys with Duchenne muscular dystrophy. Surgery resulted in increased ankle dorsiflexion range at 12 months but functional outcomes favoured the control group. By 24 months, many boys in the surgical group experienced a relapse of achilles tendon contractures. There is no evidence of significant benefit from any intervention for increasing ankle range of motion in Charcot-Marie-Tooth disease type 1A or Duchenne muscular dystrophy. Further research is required.",
        "gold": "The purpose of this review was to assess the evidence regarding the effectiveness of interventions for improving ankle flexibility in people with neuromuscular disease. Four studies were included in the review involving a total of 149 participants. Two studies showed that wearing a night splint was no more effective than not wearing a night splint for increasing ankle flexibility in 26 people who had Charcot-Marie-Tooth disease type 1A. One study showed corticosteroids (prednisone) did not significantly improve ankle flexibility in 103 boys with Duchenne muscular dystrophy and the other study showed that while orthopaedic surgery initially increased ankle flexibility in 20 young boys with Duchenne muscular dystrophy this was not sustained in the long term. This review shows that, currently, there is limited evidence supporting any intervention for improving ankle flexibility in patients with Charcot-Marie-Tooth disease type 1A and Duchenne muscular dystrophy. More research is needed."
    },
    {
        "index": "cochrane-simplification-test-307",
        "sentence": "Results should be interpreted with caution as the methodological quality of the 25 included trials (5218 women) was variable. For Comparison 1: Upright and ambulant positions versus recumbent positions and bed care, the first stage of labour was approximately one hour and 22 minutes shorter for women randomised to upright as opposed to recumbent positions (average MD -1.36, 95% confidence interval (CI) -2.22 to -0.51; 15 studies, 2503 women; random-effects, T2 = 2.39, Chi2 = 203.55, df = 14, (P < 0.00001), I2 = 93%). Women who were upright were also less likely to have caesarean section (RR 0.71, 95% CI 0.54 to 0.94; 14 studies, 2682 women) and less likely to have an epidural (RR 0.81, 95% CI 0.66 to 0.99, nine studies, 2107 women; random-effects, T2 = 0.02, I2 = 61%). Babies of mothers who were upright were less likely to be admitted to the neonatal intensive care unit, however this was based on one trial (RR 0.20, 95% CI 0.04 to 0.89, one study, 200 women). There were no significant differences between groups for other outcomes including duration of the second stage of labour, or other outcomes related to the well being of mothers and babies. For Comparison 2: Upright and ambulant positions versus recumbent positions and bed care (with epidural: all women), there were no significant differences between groups for outcomes including duration of the second stage of labour, or other outcomes related to the well being of mothers and babies. There is clear and important evidence that walking and upright positions in the first stage of labour reduces the duration of labour, the risk of caesarean birth, the need for epidural, and does not seem to be associated with increased intervention or negative effects on mothers' and babies' well being. Given the great heterogeneity and high performance bias of study situations, better quality trials are still required to confirm with any confidence the true risks and benefits of upright and mobile positions compared with recumbent positions for all women. Based on the current findings, we recommend that women in low-risk labour should be informed of the benefits of upright positions, and encouraged and assisted to assume whatever positions they choose.",
        "gold": "This review included 25 studies (involving 5218 women). Although many studies were not of high quality, and most of the women were low risk, they did show that the first stage of labour may be approximately one hour and twenty minutes shorter for women who are upright or walk around. As every contraction is potentially painful, and prolonged labour can be an overwhelming and exhausting process resulting in an increased need for medical intervention, this is a meaningful outcome for women. Indeed other important outcomes for women who were upright and mobile compared with lying down in bed included a reduction in the risk of caesarean birth, less use of epidural as a method of pain relief, and less chance of their babies being admitted to the neonatal unit. More research of better quality is still needed to validate these results for all women in labour. However, based on the results of this review we recommend that wherever possible, women should be encouraged and supported to use upright and mobile positions of their choice during first stage labour, as this may enhance the progress of their labour and may lead to better outcomes for themselves and their babies."
    },
    {
        "index": "cochrane-simplification-test-308",
        "sentence": "This review was complicated by a lack of generally accepted criteria for the diagnosis of TOS and had to rely exclusively on the diagnosis of TOS by the investigators in the reviewed studies. We identified one study comparing natural progression with an active intervention. We found three randomized controlled trials (RCTs), but only two of them had a follow-up of six months or more, which was the minimum required follow-up for inclusion in the review. The first trial that met our requirements involved 55 participants with the 'disputed type' of TOS and compared transaxillary first rib resection (TFRR) with supraclavicular neuroplasty of the brachial plexus (SNBP). The trial had a high risk of bias. TFRR decreased pain more than SNBP. There were no adverse effects in either group. The second trial that met these requirements analyzed 37 people with TOS of any type, comparing treatment with a botulinum toxin (BTX) injection into the scalene muscles with a saline placebo injection. This trial had a low risk of bias. There was no significant effect of treatment with the BTX injection over placebo in terms of pain relief or improvements in disability, but it did significantly improve paresthesias at six months' follow-up. There were no adverse events of the BTX treatment above saline injection. This review was complicated by a lack of generally accepted diagnostic criteria for the diagnosis of TOS. There was very low quality evidence that transaxillary first rib resection decreased pain more than supraclavicular neuroplasty, but no randomized evidence that either is better than no treatment. There is moderate evidence to suggest that treatment with BTX injections yielded no great improvements over placebo injections of saline. There is no evidence from RCTs for the use of other currently used treatments. There is a need for an agreed definition for the diagnosis of TOS, especially the disputed form, agreed outcome measures, and high quality randomized trials that compare the outcome of interventions with no treatment and with each other.",
        "gold": "From our systematic search we identified two trials. One trial compared surgery to remove the first rib (transaxillary first rib resection) with surgery in which the surgeon freed the nerves from surrounding tissues (neuroplasty) without removing a rib, in 55 people with the disputed type of TOS. The participants had not responded to non-surgical treatments. Average follow-up was 37 months. A second trial analyzed 19 people who underwent double-blinded provision of a single injection of BTX (muscle relaxant) into the scalene muscles of the neck, and 18 people in the placebo group who received no active injection, with follow-up at six weeks, three months and, critically for the purpose of this review, six months. There is very low quality evidence that removal of a rib reduced pain from 'disputed' TOS more than a neuroplasty procedure. We identified issues in study design that could have affected the outcome of the trial. There were no adverse effects in either group. There were no trials of surgery versus no treatment. The trial comparing the intervention of BTX injection with placebo provided moderate evidence that this procedure does not significantly reduce pain or disability scores long term, although there were no adverse events associated with the procedure over placebo. This systematic review demonstrated that there is not enough evidence that the established interventions for TOS are helpful in relieving pain. Until high quality, randomized clinical trials comparing the various interventions for TOS are performed, the decision whether to treat and the choice of appropriate treatment will have to be based on the preferences of the individual and health care provider. The evidence is current to June 2014."
    },
    {
        "index": "cochrane-simplification-test-309",
        "sentence": "Twenty-one trials involving 884 people were included. A hand brace significantly improved symptoms after four weeks (weighted mean difference (WMD) -1.07; 95% confidence interval (CI) -1.29 to -0.85) and function (WMD -0.55; 95% CI -0.82 to -0.28). In an analysis of pooled data from two trials (63 participants) ultrasound treatment for two weeks was not significantly beneficial. However one trial showed significant symptom improvement after seven weeks of ultrasound (WMD -0.99; 95% CI -1.77 to - 0.21) which was maintained at six months (WMD -1.86; 95% CI -2.67 to -1.05). Four trials involving 193 people examined various oral medications (steroids, diuretics, nonsteroidal anti-inflammatory drugs) versus placebo. Compared to placebo, pooled data for two-week oral steroid treatment demonstrated a significant improvement in symptoms (WMD -7.23; 95% CI -10.31 to -4.14). One trial also showed improvement after four weeks (WMD -10.8; 95% CI -15.26 to -6.34). Compared to placebo, diuretics or nonsteroidal anti-inflammatory drugs did not demonstrate significant benefit. In two trials involving 50 people, vitamin B6 did not significantly improve overall symptoms. In one trial involving 51 people yoga significantly reduced pain after eight weeks (WMD -1.40; 95% CI -2.73 to -0.07) compared with wrist splinting. In one trial involving 21 people carpal bone mobilisation significantly improved symptoms after three weeks (WMD -1.43; 95% CI -2.19 to -0.67) compared to no treatment. In one trial involving 50 people with diabetes, steroid and insulin injections significantly improved symptoms over eight weeks compared with steroid and placebo injections. Two trials involving 105 people compared ergonomic keyboards versus control and demonstrated equivocal results for pain and function. Trials of magnet therapy, laser acupuncture, exercise or chiropractic care did not demonstrate symptom benefit when compared to placebo or control. Current evidence shows significant short-term benefit from oral steroids, splinting, ultrasound, yoga and carpal bone mobilisation. Other non-surgical treatments do not produce significant benefit. More trials are needed to compare treatments and ascertain the duration of benefit.",
        "gold": "Other Cochrane reviews show benefit from nerve decompression surgery and steroids. This review of other non-surgical treatments found some evidence of short-term benefit from oral steroids, splinting/hand braces, ultrasound, yoga and carpal bone mobilisation (movement of the bones and tissues in the wrist), and insulin and steroid injections for people who also had diabetes. Evidence on ergonomic keyboards and vitamin B6 is unclear, while trials so far have not shown benefit from diuretics, non-steroidal anti-inflammatory drugs, magnets, laser acupuncture, exercise or chiropractic."
    },
    {
        "index": "cochrane-simplification-test-310",
        "sentence": "We included two RCTs that enrolled a total of 708 participants with CRVO-ME. SCORE compared triamcinolone acetonide intravitreal injections (n = 165) with observation (n = 72); GENEVA compared dexamethasone intravitreal implants (n = 290) with sham injections (n = 147). We observed characteristics indicative of high risk of bias due to incomplete outcome data in SCORE and selective outcome reporting in GENEVA. Loss to follow-up was high with 10% in the steroid groups and almost twice as much (17%) in the observation group. GENEVA enrolled participants with both branch and central retinal vein occlusion, but did not present subgroup data for the CRVO-ME population. A qualitative assessment of the results from GENEVA indicated that the dexamethasone implant was not associated with improvement in visual acuity after six months among participants with CRVO-ME. Although the SCORE investigators reported that participants treated with 1 mg (n = 82) or 4 mg (n = 83) triamcinolone intravitreal injections were five times more likely to have gained 15 letters or more in visual acuity compared with participants in the observation group (1 mg; risk ratio (RR): 5.27; 95% confidence interval (CI) 1.62 to 17.15; 4 mg RR 4.92; 95% CI 1.50 to 16.10) by the eighth-month follow-up examination, the average visual acuity decreased in all three groups. However, eyes treated with triamcinolone lost fewer letters than participants in the observation group at 8 months (1 mg mean difference (MD): 8.70 letters, 95% CI 1.86 to 15.54; 4 mg MD: 9.80 letters, 95% CI 3.32 to 16.28). A higher incidence of adverse events was noted with IVS therapy when compared with observation alone. As many as 20% to 35% of participants experienced an adverse event in the IVS groups compared with 8% of participants in the observation group of the SCORE study. The GENEVA investigators reported 63% in the treatment arm versus 43% in the observation arm experienced an adverse event. The most commonly encountered adverse events were elevated intraocular pressure, progression of cataracts, and retinal neovascularization. We graded the quality of evidence as low due to study limitations, imprecision of treatment estimates, and selective outcome reporting. The two RCTs reviewed herein provide insufficient evidence to determine the benefits of IVS for individuals with CRVO-ME. The improvement in visual acuity noted in the SCORE trial should be interpreted with caution as outcome data were missing for a large proportion of the observation group. Adverse events were observed more often with IVS treatment compared with observation/no treatment.",
        "gold": "The review authors searched the medical literature up to 13 November 2014 and included two randomized controlled trials (GENEVA and SCORE) that had evaluated steroids in 708 participants with CRVO-ME. Both trials included participants with similar baseline characteristics with respect to age, gender, and co-morbidities. GENEVA was conducted in 24 countries across the world and SCORE was conducted in the US. Both trials compared two different doses of steroid, but the investigators of the two trials used different steroidal agents and different methods of delivery (implant versus injection). Both trials received full or partial sponsorship from the manufacturer of the drugs. Neither trial provided sufficient evidence to determine whether steroids had improved visual acuity after six months of treatment. Due to the limited evidence, we are unable to determine reliably whether steroid implants improved vision in eyes with CRVO-ME. Although the SCORE trial showed that more eyes in the steroid injection groups had improvement in vision compared with eyes in the observation group, participants treated with steroids and those not treated with steroids both lost vision on average at eight months. The GENEVA investigators reported no difference in vision outcomes between participants treated with steroids and those not treated with steroids after six months of treatment; however the GENEVA study was not limited to participants with only CRVO-ME and included participants with other retinal disease. Both trials showed that patients treated with steroids were at increased risk for high eye pressure - requiring additional medications to lower the eye pressure - and developing cataracts. The overall quality of the evidence was low due to clinical differences between studies, incomplete information available to assess outcomes, and lack of masking which may lead to biased study results."
    },
    {
        "index": "cochrane-simplification-test-311",
        "sentence": "Six randomised trials involving a total of 394 patients were included. Five of the six trials demonstrated a significant efficacy of intranasal corticosteroids in improving nasal obstruction symptoms and in reducing adenoid size. The first eight-week cross-over study showed that treatment with beclomethasone (336 mcg/day) yielded a greater improvement in mean symptom scores than placebo (-18.5 versus -8.5, P < 0.05) and a larger reduction in mean adenoid/choana ratio than placebo (right, -14% versus +0.4%, P = 0.002; left, -15% versus -2.0%, P = 0.0006) between week 0 and week 4. The second four-week cross-over study showed that the Nasal Obstruction Index decreased by at least 50% from baseline in 38% of patients treated with beclomethasone (400 mcg/day) between week 0 and week 2, whereas none of the patients treated with placebo had such improvement (P < 0.01). The third parallel-group trial showed that 77.7% of patients treated with mometasone (100 mcg/day) for 40 days demonstrated an improvement in nasal obstruction symptoms and a decrease in adenoid size, such that adenoidectomy could be avoided, whereas no significant improvement was observed in the placebo group. The fourth parallel-group trial showed that eight weeks of treatment with flunisolide (500 mcg/day) was associated with a larger reduction in adenoid size than isotonic saline solution (P < 0.05). The fifth parallel-group trial demonstrated that eight weeks of treatment with fluticasone (400 mcg/day) significantly reduced nasal obstruction symptoms and adenoid size, and adenoidectomy was avoided in 76% of these patients compared with 20% of the patients treated with normal saline (P < 0.05). In contrast, one parallel-group trial did not find a significant improvement in nasal obstruction symptoms nor adenoid size after eight weeks of treatment with beclomethasone (200 mcg/day). Current evidence suggests that intranasal corticosteroids may significantly improve nasal obstruction symptoms in children with moderate to severe adenoidal hypertrophy, and this improvement may be associated with a reduction in adenoid size. The long-term efficacy of intranasal corticosteroids in these patients remains to be defined.",
        "gold": "This review was conducted to assess the effectiveness of intranasal corticosteroids for improving nasal airway obstruction in children aged 0 to 12 years with moderate to severe adenoidal hypertrophy. Evidence derived from five of the six randomised controlled trials included in this review suggests that intranasal steroids may significantly improve symptoms of nasal obstruction in children with adenoidal hypertrophy and that this improvement may be associated with the reduction of adenoid size. One study did not find a significant improvement in nasal obstruction symptoms. Further large and high-quality randomised controlled trials are warranted."
    },
    {
        "index": "cochrane-simplification-test-312",
        "sentence": "We included one small study (involving 24 women). The study was a single-centre randomised trial conducted in Mexico. This study compared a control group who received antihypertensive therapy, anticonvulsant therapy, plasma expanders, corticosteroids and dypyridamole with an intervention group that received epidural block instead of the antihypertensives, as well as all the other four drugs. Lumbar epidural block was given using 0.25% bupivacaine, 10 mg bolus and 5 mg each hour on continuous epidural infusion for six hours. This study was at low risk of bias in three domains but was assessed to be high risk of bias in two domains due to lack of allocation concealment and blinding of women and staff, and unclear for random sequence generation and outcome assessor blinding. The included study did not report on any of this review's important outcomes. Meta-analysis was not possible. For the mother, these were: maternal death (death during pregnancy or up to 42 days after the end of the pregnancy, or death more than 42 days after the end of the pregnancy); development of eclampsia or recurrence of seizures; stroke; any serious morbidity: defined as at least one of stroke, kidney failure, liver failure, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, pulmonary oedema. For the baby, these were: death: stillbirths (death in utero at or after 20 weeks' gestation), perinatal deaths (stillbirths plus deaths in the first week of life), death before discharge from the hospital, neonatal deaths (death within the first 28 days after birth), deaths after the first 28 days; preterm birth (defined as the birth before 37 completed weeks' gestation); and side effects of the intervention. Reported outcomes The included study only reported on a single secondary outcome of interest to this review: the Apgar score of the baby at birth and after five minutes and there was no clear difference between the intervention and control groups. The included study also reported a reduction in maternal diastolic arterial pressure. However, the change in maternal mean arterial pressure and systolic arterial pressure, which were the other reported outcomes of this trial, were not significantly different between the two groups. Currently, there is insufficient evidence from randomised controlled trials to evaluate the effectiveness, safety or cost of using epidural therapy for treating severe pre-eclampsia in non-labouring women. High-quality randomised controlled trials are needed to evaluate the use of epidural agents as therapy for treatment of severe pre-eclampsia. The rationale for the use of epidural is well-founded. However there is insufficient evidence from randomised controlled trials to show that the effect of epidural translates into improved maternal and fetal outcomes. Thus, there is a need for larger, well-designed studies to come to an evidence-based conclusion as to whether the lowering of vasomotor tone by epidural therapy results in better maternal and fetal outcomes and for how long that could be maintained. Another important question that needs to be answered is how long should extended epidural be used to ensure any potential clinical benefits and what could be the associated side effects and costs. Interactions with other modalities of treatment and women's satisfaction could represent other avenues of research.",
        "gold": "We searched for evidence in July 2017 and identified one small randomised controlled study (involving 24 women) for inclusion in this review. The women were at 30 weeks of gestation or more, diagnosed with severe pre-eclampsia, and being cared for in an intensive care unit. They were randomly assigned to an epidural block plus their other medications or a drug to treat their high blood pressure plus their other medications. After six hours of treatment they all underwent a caesarean section. The included study did not report on any of the important outcomes of interest in this review such as death of the mother, death of her baby (before or after being born), serious illness for the mother or her baby, the mother developing eclampsia or seizures, or side effects of the intervention. The study authors did report difference in the infant Apgar scores between the two groups The study authors also reported a clear drop in the diastolic blood pressure in the epidural group compared to the other group. Systolic and mean blood pressures were similar in the two groups of women. However, the study did not report on any other mother or baby outcomes of interest in this review. There is not enough evidence from randomised controlled trials to evaluate the use of epidural therapy in severe pre-eclampsia to improve outcomes for the mother or her baby. High-quality trials are needed to evaluate the efficacy, safety and cost of epidural therapy in severe pre-eclampsia. Future studies could report on important outcomes such as those listed in this review."
    },
    {
        "index": "cochrane-simplification-test-313",
        "sentence": "Sixteen trials fulfilled our inclusion criteria. All trials but one were at overall high risk of bias. Fifteen trials (one of which was an abstract) provided data for analysis (927 participants received glucocorticosteroids and 934 participants received placebo or no intervention). Glucocorticosteroids were administered orally or parenterally for a median 28 days (range 3 days to 12 weeks). The participants were between 25 and 70 years old, had different stages of alcoholic liver disease, and 65% were men. Follow-up, when reported, was up to the moment of discharge from the hospital, until they died (median of 63 days), or for at least one year. There was no evidence of effect of glucocorticosteroids on all-cause mortality up to three months following randomisation (random-effects RR 0.90, 95% CI 0.70 to 1.15; participants = 1861; trials = 15; very low-certainty evidence) or on health-related quality of life up to three months, measured with the European Quality of Life \u2013 5 Dimensions \u2013 3 Levels scale (MD \u20130.04 points, 95% CI \u20130.11 to 0.03; participants = 377; trial = 1; low-certainty evidence). There was no evidence of effect on the occurrence of serious adverse events during treatment (random-effects RR 1.05, 95% CI 0.85 to 1.29; participants = 1861; trials = 15; very low-certainty evidence), liver-related mortality up to three months following randomisation (random-effects RR 0.89, 95% CI 0.69 to 1.14; participants = 1861; trials = 15; very low-certainty evidence), number of participants with any complications up to three months following randomisation (random-effects RR 1.04, 95% CI 0.86 to 1.27; participants = 1861; very low-certainty evidence), and number of participants of non-serious adverse events up to three months' follow-up after end of treatment (random-effects RR 1.99, 95% CI 0.72 to 5.48; participants = 160; trials = 4; very low-certainty evidence). Based on the information that we collected from the published trial reports, only one of the trials seems not to be industry-funded, and the remaining 15 trials did not report clearly whether they were partly or completely funded by the industry. We are very uncertain about the effect estimate of no difference between glucocorticosteroids and placebo or no intervention on all-cause mortality and serious adverse events during treatment because the certainty of evidence was very low, and low for health-related quality of life. Due to inadequate reporting, we cannot exclude increases in adverse events. As the CIs were wide, we cannot rule out significant benefits or harms of glucocorticosteroids. Therefore, we need placebo-controlled randomised clinical trials, designed according to the SPIRIT guidelines and reported according to the CONSORT guidelines. Future trials ought to report depersonalised individual participant data, so that proper individual participant data meta-analyses of the effects of glucocorticosteroids in subgroups can be conducted.",
        "gold": "Sixteen randomised clinical trials compared glucocorticosteroids with placebo or no intervention in people with alcoholic hepatitis. Fifteen trials provided data for analysis (927 participants received glucocorticosteroids and 934 participants received placebo or no intervention). Glucocorticosteroids were administered orally or as an injection for a median of 28 days (range 3 days to 12 weeks). The trial participants were between 25 and 70 years old, 65% were men, and had different stages of alcoholic liver disease. Trial participants were followed up to the moment of discharge from the hospital, or until they died (a median of 63 days), or for at least one year. Not all trials reported the follow-up of participants. The trials were conducted in France, India, the UK, and the USA. Two trials administered pentoxifylline (a medicine used for diseases of the blood vessels) to both glucocorticosteroids and placebo intervention groups. Based on the information that we collected from the published trial reports, only one of the trials seems not to be industry-funded, and the remaining 15 trials did not report clearly whether they were partly or completely funded by the industry. The overall reliability of the evidence was low for health-related quality of life and very low for death due to any cause up to three months following entry in the trial; serious side effects during treatment; liver-related death up to three months following entry in the trial; number of participants with any complications up to three months following entry in the trial, and number of participants non-serious side effects up to three months' follow-up after the end of treatment. All trials but one were at overall high risk of bias, which means that there is possibility of drawing wrong conclusions, exaggerating benefits, or underestimating harms of glucocorticosteroids because of the way the trials were conducted and analysed. We could not determine whether glucocorticosteroids had a positive or negative effect on people with alcoholic liver disease. Despite available data on outcomes which included mortality, health-related quality of life, and serious complications, we were unable to draw firm conclusions mainly because available data were still insufficient to produce robust results, trials were small, and the included participants differed in severity of disease. Therefore, we have very little confidence in our conclusions."
    },
    {
        "index": "cochrane-simplification-test-314",
        "sentence": "We included four trials involving 245 participants in the review. Study sample sizes were generally small, and interventions, controls and outcome measures varied, and thus it was inappropriate to pool studies. Included studies were at a low risk of bias for the majority of domains, with a high/unclear risk of bias identified in the areas of: performance (participants not blinded to allocation), and attrition (incomplete outcome data due to withdrawal) bias. Intervention approaches included the contextual approach of driving simulation and underlying skill development approach, including the retraining of speed of visual processing and visual motor skills. The studies were conducted with people who were relatively young and the timing after stroke was varied. Primary outcome: there was no clear evidence of improved on-road scores immediately after training in any of the four studies, or at six months (mean difference 15 points on the Test Ride for Investigating Practical Fitness to Drive - Belgian version, 95% confidence intervals (CI) 4.56 to 34.56, P value = 0.15, one study, 83 participants). Secondary outcomes: road sign recognition was better in people who underwent training compared with control (mean difference 1.69 points on the Road Sign Recognition Task of the Stroke Driver Screening Assessment, 95% CI 0.51 to 2.87, P value = 0.007, one study, 73 participants). Significant findings were in favour of a simulator-based driving rehabilitation programme (based on one study with 73 participants) but these results should be interpreted with caution as they were based on a single study. Adverse effects were not reported. There was insufficient evidence to draw conclusions on the effects on vision, other measures of cognition, motor and functional activities, and driving behaviour with the intervention. There was insufficient evidence to reach conclusions about the use of rehabilitation to improve on-road driving skills after stroke. We found limited evidence that the use of a driving simulator may be beneficial in improving visuocognitive abilities, such as road sign recognition that are related to driving. Moreover, we were unable to find any RCTs that evaluated on-road driving lessons as an intervention. At present, it is unclear which impairments that influence driving ability after stroke are amenable to rehabilitation, and whether the contextual or remedial approaches, or a combination of both, are more efficacious.",
        "gold": "We identified four studies, up to October 2013, which involved 245 people after stroke. A wide range of interventions was used, including driving simulation, training on devices to improve speed of processing information, scanning and movement. All studies compared the effectiveness of the driving intervention on improving whether drivers passed or failed on a driving assessment. There was no evidence that a driving intervention was more effective than no intervention. One trial found that training on a driving simulator resulted in improved performance on a test of recognising road signs immediately after training. Results should be interpreted with caution, as this was a single study. Further trials involving large numbers of participants, grouped according to their impairments and stroke type are required."
    },
    {
        "index": "cochrane-simplification-test-315",
        "sentence": "Eight studies with 582 participants met the inclusion criteria, of which five studies conducted in hospitals with 519 participants (range 28 to 296) contributed to the meta-analysis. Mean ages of study participants were 65 to 73 years, the proportion of male participants varied (58% to 84%) and COPD was classified as severe or very severe. Corticosteroid treatment was given at equivalent daily doses for three to seven days for short-duration treatment and for 10 to 15 days for longer-duration treatment. Five studies administered oral prednisolone (30 mg in four, tapered in one), and two studies provided intravenous corticosteroid treatment. Studies contributing to the meta-analysis were at low risk of selection, performance, detection and attrition bias. In four studies we did not find a difference in risk of treatment failure between short-duration and longer-duration systemic corticosteroid treatment (n = 457; odds ratio (OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46)), which was equivalent to 22 fewer per 1000 for short-duration treatment (95% CI 51 fewer to 34 more). No difference in risk of relapse (a new event) was observed between short-duration and longer-duration systemic corticosteroid treatment (n = 457; OR 1.04, 95% CI 0.70 to 1.56), which was equivalent to nine fewer per 1000 for short-duration treatment (95% CI 68 fewer to 100 more). Time to the next COPD exacerbation did not differ in one large study that was powered to detect non-inferiority and compared five days versus 14 days of systemic corticosteroid treatment (n = 311; hazard ratio 0.95, 95% CI 0.66 to 1.37). In five studies no difference in the likelihood of an adverse event was found between short-duration and longer-duration systemic corticosteroid treatment (n = 503; OR 0.89, 95% CI 0.46 to 1.69, or nine fewer per 1000 (95% CI 44 fewer to 51 more)). Length of hospital stay (n = 421; mean difference (MD) -0.61 days, 95% CI -1.51 to 0.28) and lung function at the end of treatment (n = 185; MD FEV1 -0.04 L; 95% CI -0.19 to 0.10) did not differ between short-duration and longer-duration treatment. Information from a new large study has increased our confidence that five days of oral corticosteroids is likely to be sufficient for treatment of adults with acute exacerbations of COPD, and this review suggests that the likelihood is low that shorter courses of systemic corticosteroids (of around five days) lead to worse outcomes than are seen with longer (10 to 14 days) courses. We graded most available evidence as moderate in quality because of imprecision; further research may have an important impact on our confidence in the estimates of effect or may change the estimates. The studies in this review did not include people with mild or moderate COPD; further studies comparing short-duration systemic corticosteroid versus conventional longer-duration systemic corticosteroid for treatment of adults with acute exacerbations of COPD are required.",
        "gold": "We found eight studies that included 582 people with COPD who experienced a flare-up that required extra treatment in hospital. These studies compared oral or injected corticosteroid treatment given for seven or fewer days versus treatment for longer than seven days. Most of the people in these studies were in their late sixties and had severe or very severe symptoms of COPD; more men than women took part. The last search for studies to be included in the review was conducted in March 2017. No differences were observed between shorter and longer courses of treatment. People treated for seven or fewer days did not have a higher rate of treatment failure or longer time to their next exacerbation; the number of people who avoided treatment failure ranged from 51 fewer to 34 more per 1000 treated (average 22 fewer people per 1000). Time in hospital and lung function (blowing tests) at the end of treatment were not different. No differences in side effects or death were noted between treatments. Information on quality of life, which is an important outcome for people with COPD, is limited, as only one study measured it. The eight studies included in this review were generally well designed, and the quality of the evidence was rated as moderate because of imprecision in results; more research, especially involving people with less severe COPD, is needed."
    },
    {
        "index": "cochrane-simplification-test-316",
        "sentence": "We included one trial (13 participants) and identified three ongoing trials that assess RBC transfusion strategies in people with MDS. The quality of the evidence was very low across different outcomes according to GRADE methodology. The one included study randomised participants to a restrictive [haemoglobin (Hb) transfusion trigger < 72 g/L, 8 participants] or liberal [Hb trigger < 96 g/L, 5 participants] transfusion policy. There was insufficient evidence to determine a difference in all-cause mortality (1 RCT; 13 participants; RR 0.13, 95% CI 0.01 to 2.32; very low quality evidence). There was insufficient evidence to determine a difference in the number of red blood cell transfusions (1 RCT; 13 participants; 1.8 units per patient per month in the liberal group, compared to 0.8 in the restrictive arm, no standard deviation was reported; very low quality evidence). There were no anaemia-related complications reported (cardiac failure) and no reported effect on activity levels (no statistics provided). The study did not report: mortality due to bleeding/infection/transfusion reactions or iron overload, quality of life, frequency and length of hospital admissions, serious infections (requiring admission to hospital), or serious bleeding (e.g. WHO/CTCAE grade 3 (or equivalent) or above). This review indicates that there is currently a lack of evidence for the recommendation of a particular transfusion strategy for bone marrow failure patients undergoing supportive treatment only. The one RCT included in this review was only published as an abstract and contained only 13 participants. Further randomised trials with robust methodology are required to develop the optimal transfusion strategy for such patients, particularly as the incidence of the main group of bone marrow failure disorders, MDS, rises with an ageing population.",
        "gold": "Only one small study including 13 patients with bone marrow failure was included in this review. The study was funded by two government agencies and one charity. We are aware of three ongoing studies which have not yet been completed. The evidence is current to 26th May 2015. The one included study was too small to demonstrate any difference in all-cause mortality (death due to any cause) or number of red cell transfusions received between a restrictive compared to a liberal red blood cell transfusion policy. At the current time, there is a lack of evidence to recommend a restrictive transfusion strategy over a liberal one. Trials with good methodology are needed to determine the best transfusion policy for patients with long -term bone marrow failure disorders. The evidence for the findings was of very low quality. This was because very small numbers of participants were included in the study. Only 13 patients were recruited to the trial rather than the planned 200 participants due to problems with recruitment."
    },
    {
        "index": "cochrane-simplification-test-317",
        "sentence": "The search strategy identified a total of 2079 unique citations. Out of 84 potentially eligible citations, we included two RCTs. The game evaluated in the first study used as a reinforcement technique, was based on the television game show \"Family Feud\" and focused on infection control. The study did not assess any patient or process of care outcomes. The group that was randomized to the game had statistically higher scores on the knowledge test (P = 0.02). The second study compared game-based learning (\"Snakes and Ladders\" board game) with traditional case-based learning of stroke prevention and management. The effect on knowledge was not statistically different between the two groups immediately and 3 months after the intervention. The level of reported enjoyment was higher in the game-based group. The findings of this systematic review neither confirm nor refute the utility of games as a teaching strategy for health professionals. There is a need for additional high-quality research to explore the impact of educational games on patient and performance outcomes.",
        "gold": "This review found two eligible studies. The first study evaluated a game based on the TV show Family Feud and taught about infection control. The second study evaluated the use of a \"Snakes and Ladders\" board game in continuing medical education on stroke prevention and management. The two studies did not consistently show a beneficial effect on knowledge. We are therefore very uncertain whether games improve health care professional practice or patient care."
    },
    {
        "index": "cochrane-simplification-test-318",
        "sentence": "Eight trials involving 475 people were included. Two of the studies included a mixed group of participants with either bipolar or unipolar disorder. Relapse was defined as admission to hospital and when all kinds of relapses were considered (both depressive and manic), there was a statistically significant difference in favour of lithium (relative risk (RR) fixed effect 0.34, 95% CI 0.14 to 0.82). The results did not exclude the point of no effect, when the random-effects model was used (RR random effects 0.40, 95% CI 0.14 to 1.18). There were no other statistically significant differences between lithium and antidepressants according to all other outcomes considered. Manic or depressive relapse was defined as prescription of non-study medication for mood disorder, manic or depressive relapse (as defined by the study authors), quality of life, social functioning, occupational functioning, overall drop-out rate, drop-out rate due to side-effects, troublesome side-effects, mortality due to all causes and specifically suicides. There was adequate efficacy evidence for lithium or antidepressants preventing relapse in unipolar affective disorder, however their relative efficacy was unknown. When considering lithium or antidepressant long-term therapy, patients and clinicians should take into account the patient's clinical history, the side-effects and the individual's likely adherence to the recommended treatment regime. Large-scale, long-term randomised trials in unselected groups of subjects with unipolar affective disorder are needed.",
        "gold": "This systematic review investigated the efficacy and tolerability of lithium compared to antidepressants for the long-term treatment of unipolar affective disorder. Eight randomised studies (reporting on 475 participants) were included in the review. We found no reliable evidence of any robust differences between lithium and antidepressants but nor could we reliably exclude the possibility of clinically significant differences. In this review some studies included a mixed group of participants with either bipolar or unipolar disorder. The review suggests that, while lithium may be of benefit in preventing relapse in unipolar affective disorder, there remains uncertainty about the treatment effect in comparison with antidepressants. Interpretation of this review should consider that the number of participants in the studies was small and the included studies had methodological shortcomings."
    },
    {
        "index": "cochrane-simplification-test-319",
        "sentence": "Two trials with 130 patients (67 and 63 patients randomised to intervention versus control) were included. Both studies had a low risk of bias.\u00a0Amifostine versus placebo showed no statistically significant differences in the incidence of xerostomia (130 patients, two studies), the decrease of scintigraphically measured uptake of technetium-99m by salivary or submandibular glands at twelve months (80 patients, one study), and the reduction of blood pressure (130 patients, two studies).\u00a0Two patients in one study collapsed after initiation of amifostine therapy and had to be treated by withdrawing the infusion and volume substitution. Both patients recovered without sequelae. Meta-analysis was not performed on the function of salivary glands measured by technetium-99m scintigraphy at three months after high dose radioactive iodine treatment due to the highly inconsistent findings across studies (I2 statistic 99%). None of the included trials investigated death from any cause, morbidity, health-related quality of life or costs. Results from two randomised controlled clinical trials suggest that the amifostine has no significant radioprotective effects on salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer patients. Moreover, no health-related quality of life and other patient-oriented outcomes were evaluated in the two included trials. Randomised controlled clinical trials with low risk of bias investigating patient-oriented outcomes are needed to guide treatment choice.",
        "gold": "We found only two randomised controlled trials in which the effects of amifostine were compared with placebo. The two randomised clinical trials investigated 130 patients treated with high dose radioactive iodine for thyroid cancer. Altogether data from the two trials suggest that amifostine has no obvious protective effects on the salivary glands in these patients. Two patients in one study collapsed after initiation of amifostine therapy and had to be treated by withdrawing the infusion and volume substitution. Both patients recovered without sequelae. Until better data become available, the use of sour candy or lemon juice to increase salivation might be more appropriate during radioactive iodine treatment for patients with differentiated thyroid cancer. Patients should be well informed of the importance of hydration, acid stimulation and glandular massage after radioactive iodine treatment. In addition, early recognition and treatment of xerostomia may improve outcomes."
    },
    {
        "index": "cochrane-simplification-test-320",
        "sentence": "We included three studies involving 45 children aged between 29 months and six years with Down syndrome. Two studies compared parent-mediated interventions versus TAU; the third compared a parent-mediated plus clinician-mediated intervention versus a clinician-mediated intervention alone. Treatment duration varied from 12 weeks to six months. One study provided nine group sessions and four individualised home-based sessions over a 13-week period. Another study provided weekly, individual clinic-based or home-based sessions lasting 1.5 to 2 hours, over a six-month period. The third study provided one 2- to 3-hour group session followed by bi-weekly, individual clinic-based sessions plus once-weekly home-based sessions for 12 weeks. Because of the different study designs and outcome measures used, we were unable to conduct a meta-analysis. We judged all three studies to be at high risk of bias in relation to blinding of participants (not possible due to the nature of the intervention) and blinding of outcome assessors, and at an unclear risk of bias for allocation concealment. We judged one study to be at unclear risk of selection bias, as authors did not report the methods used to generate the random sequence; at high risk of reporting bias, as they did not report on one assessed outcome; and at high risk of detection bias, as the control group had a cointervention and only parents in the intervention group were made aware of the target words for their children. The sample sizes of each included study were very small, meaning that they are unlikely to be representative of the target population. The findings from the three included studies were inconsistent. Two studies found no differences in expressive or receptive language abilities between the groups, whether measured by direct assessment or parent reports. However, they did find that children in the intervention group could use more targeted vocabulary items or utterances with language targets in certain contexts postintervention, compared to those in the control group; this was not maintained 12 months later. The third study found gains for the intervention group on total-language measures immediately postintervention. One study did not find any differences in parental stress scores between the groups at any time point up to 12 months postintervention. All three studies noted differences in most measures of how the parents talked to and interacted with their children postintervention, and in one study most strategies were maintained in the intervention group at 12 months postintervention. No study reported evidence of language attrition following the intervention in either group, while one study found positive outcomes on children's socialisation skills in the intervention group. One study looked at adherence to the treatment through attendance data, finding that mothers in the intervention group attended seven out of nine group sessions and were present for four home visits. No study measured parental use of the strategies outside of the intervention sessions. A grant from the Hospital for Sick Children Foundation (Toronto, Ontario, Canada) funded one study. Another received partial funding from the National Institute of Child Health and Human Development and the Department of Education in the USA. The remaining study did not specify any funding sources. In light of the serious limitations in methodology, and the small number of studies included, we considered the overall quality of the evidence, as assessed by GRADE, to be very low. This means that we have very little confidence in the results, and further research is very likely to have an important impact on our confidence in the estimate of treatment effect. There is currently insufficient evidence to determine the effects of parent-mediated interventions for improving the language and communication of children with Down syndrome. We found only three small studies of very low quality. This review highlights the need for well-designed studies, including RCTs, to evaluate the effectiveness of parent-mediated interventions. Trials should use valid, reliable and similar measures of language development, and they should include measures of secondary outcomes more distal to the intervention, such as family well-being. Treatment fidelity, in particular parental dosage of the intervention outside of prescribed sessions, also needs to be documented.",
        "gold": "The evidence is current to January 2018. We found three studies involving 45 children aged between 29 months and six years. Two studies were randomised controlled trials: experiments in which children were allocated to treatment (i.e. parent-mediated) and control (treatment as usual or clinician-mediated, or both) groups using a random method such as a computer-generated list of random numbers. The other study reported that randomisation took place but did not specify how this was done. Two studies compared parent-mediated intervention to treatment as usual. One of these lasted for 13 weeks, and parents in the intervention group received nine, weekly group sessions and four individual sessions in the home. The total intervention time was approximately 26.5 hours. A second study lasted for six months, and parents received weekly, 1.5- to 2-hour clinic or home-based, individualised, parent-child sessions. The total intervention time was approximately 48 hours. A third study compared a parent- and clinician-mediated intervention to a clinician-only-mediated intervention. In this study the parents in the intervention group took part in a two- to three-hour interactive workshop plus three individualised sessions (two clinic-based and one home-based) every week for 12 weeks. The control group received the same individualised sessions, but a clinician delivered them (i.e. there was no parental involvement). The total intervention time was approximately 19 hours. A grant from the Hospital for Sick Children Foundation (Toronto, Ontario, Canada) funded one study. Another received partial funding from the National Institute of Child Health and Human Development and the Department of Education in the USA. The remaining study did not specify any funding sources. Two of the three studies found no differences in children's language ability after parent training. However, these same two studies found that children in the intervention group used more words that had been specifically targeted, postintervention; this was not maintained 12 months later. The study that gave parents the largest amount of intervention reported gains on general measures of overall language ability for children in the intervention group. One study did not find any changes in levels of parental stress immediately or up to 12 months postintervention in either group. All three studies noted changes in how parents talked to and interacted with their children immediately postintervention, and most strategies were retained by the intervention group 12 months later. One study reported increases in the socialisation skills of children who received the intervention. No study reported language attrition in either group postintervention. We rated the quality of the evidence in this review as very low, as only three studies fulfilled the criteria for inclusion, and all had small sizes and serious methodological limitations. There is currently insufficient evidence to determine the effect of parent-mediated interventions for improving the communication and language development in young children with Down syndrome."
    },
    {
        "index": "cochrane-simplification-test-321",
        "sentence": "We included two trials from 1987 and 2004 with a total 148 participants who have had heart valve surgery. Both trials had a high risk of bias. There was insufficient evidence at 3 to 6 months follow-up to judge the effect of exercise-based cardiac rehabilitation compared to no exercise on mortality (RR 4.46 (95% confidence interval (CI) 0.22 to 90.78); participants = 104; studies = 1; quality of evidence: very low) and on serious adverse events (RR 1.15 (95% CI 0.37 to 3.62); participants = 148; studies = 2; quality of evidence: very low). Included trials did not report on health-related quality of life (HRQoL), and the secondary outcomes of New York Heart Association class, left ventricular ejection fraction and cost. We did find that, compared with control (no exercise), exercise-based rehabilitation may increase exercise capacity (SMD -0.47, 95% CI -0.81 to -0.13; participants = 140; studies = 2, quality of evidence: moderate). There was insufficient evidence at 12 months follow-up for the return to work outcome (RR 0.55 (95% CI 0.19 to 1.56); participants = 44; studies = 1; quality of evidence: low). Due to limited information, trial sequential analysis could not be performed as planned. Our findings suggest that exercise-based rehabilitation for adults after heart valve surgery, compared with no exercise, may improve exercise capacity. Due to a lack of evidence, we cannot evaluate the impact on other outcomes. Further high-quality randomised clinical trials are needed in order to assess the impact of exercise-based rehabilitation on patient-relevant outcomes, including mortality and quality of life.",
        "gold": "We searched for randomised clinical trials (experiments in which participants are randomly allocated to an experimental compared with a control intervention) examining the effect of exercise-based cardiac rehabilitation compared with no exercise after heart valve surgery for heart valve disease (from any cause) in adults (18 years or older). Our literature searches were undertaken up to March 2015. We found two randomised clinical trials published in 1987 and 2004 that included a total of 148 participants. Due to the limited amount of data, we were not able to determine the effect of exercise-based rehabilitation on mortality, serious adverse events, health-related quality of life, ability to return to work, New York Heart Association class, left ventricular ejection fraction, or cost. However, exercise-based rehabilitation did appear to increase exercise capacity at up to 12 months follow-up, although this should be interpreted with caution as the included trials had a high risk of systematic error (bias). Further randomised clinical trials are needed to definitely understand the effect of physical exercise in adults after heart valve surgery. Given that the included studies are relatively old, and included narrowly-selected trial populations, the evidence is likely to be of limited applicability to clinical practice. Both trials had a high risk of bias (systematic errors) and the quality of the evidence was low. Due to the scarcity of the evidence there is also a high risk that the results may be subject to random errors (play of chance). Therefore, further high-quality randomised clinical trials are needed to assess the effects of exercise-based interventions."
    },
    {
        "index": "cochrane-simplification-test-322",
        "sentence": "Five RCTs (1130 participants) were included. Two studies evaluated meditation, the others evaluated multi-disciplinary palliative care interventions that involved a chaplain or spiritual counsellor as a member of the intervention team. The studies evaluating meditation found no overall significant difference between those receiving meditation or usual care on quality of life or well-being. However, when meditation was combined with massage in the medium term it buffered against a reduction in quality of life. In the palliative care intervention studies there was no significant difference in quality of life or well-being between the trial arms. Coping with the disease was not evaluated in the studies. The quality of the studies was limited by under-reporting of design features. We found inconclusive evidence that interventions with spiritual or religious components for adults in the terminal phase of a disease may or may not enhance well-being. Such interventions are under-evaluated. All five studies identified were undertaken in the same country, and in the multi-disciplinary palliative care interventions it is unclear if all participants received support from a chaplain or a spiritual counsellor. Moreover, it is unclear in all the studies whether the participants in the comparative groups received spiritual or religious support, or both, as part of routine care or from elsewhere. The paucity of quality research indicates a need for more rigorous studies.",
        "gold": "Being ill and near to the end of life can raise questions such as \"Why me? Why now?\". The experience may start or increase thoughts of a spiritual or religious nature. Some research has found that having spiritual or religious awareness, or both, may help a person cope with disease and dying. We conducted our review through searches for studies that were randomised controlled trials. We only included such studies if they evaluated an intervention that involved a spiritual or religious aspect, such as prayer and meditation, and aimed to support adults in the terminal phase of a disease. We found five studies. In total, the studies involved 1130 participants. Two studies evaluated meditation. Three evaluated the work of a palliative care team that involved physicians, nurses and chaplains. Studies compared those who received the intervention with those who did not. Studies evaluated the interventions in various ways including whether it helped in any way a person's quality of life. There was inconclusive evidence that meditation and palliative care teams that involve a chaplain or spiritual counsellor help patients feel emotionally supported. The findings of the review are limited. This is because none of the studies measured whether the intervention helped the person cope with the disease process, and also it is unclear whether all participants receiving the palliative care team interventions were offered support from a chaplain. All the studies were undertaken in one country, making it difficult to draw conclusions as to whether the intervention would work elsewhere."
    },
    {
        "index": "cochrane-simplification-test-323",
        "sentence": "We included six trials with a total of 137 participants. We found two studies with 45 participants examining the effects of tDCS compared to control (sham tDCS) on our primary outcome measure, impairment, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). There was very low quality evidence for no effect of tDCS on change in global UPDRS score ( mean difference (MD) -7.10 %, 95% confidence interval (CI -19.18 to 4.97; P = 0.25, I\u00b2 = 21%, random-effects model). However, there was evidence of an effect on UPDRS part III motor subsection score at the end of the intervention phase (MD -14.43%, 95% CI -24.68 to -4.18; P = 0.006, I\u00b2 = 2%, random-effects model; very low quality evidence). One study with 25 participants measured the reduction in off and on time with dyskinesia, but there was no evidence of an effect (MD 0.10 hours, 95% CI -0.14 to 0.34; P = 0.41, I\u00b2 = 0%, random-effects model; and MD 0.00 hours, 95% CI -0.12 to 0.12; P = 1, I\u00b2 = 0%, random- effects model, respectively; very low quality evidence). Two trials with a total of 41 participants measured gait speed using measures of timed gait at the end of the intervention phase, revealing no evidence of an effect ( standardised mean difference (SMD) 0.50, 95% CI -0.17 to 1.18; P = 0.14, I\u00b2 = 11%, random-effects model; very low quality evidence). Another secondary outcome was health-related quality of life and we found one study with 25 participants reporting on the physical health and mental health aspects of health-related quality of life (MD 1.00 SF-12 score, 95% CI -5.20 to 7.20; I\u00b2 = 0%, inverse variance method with random-effects model; very low quality evidence; and MD 1.60 SF-12 score, 95% CI -5.08 to 8.28; I\u00b2 = 0%, inverse variance method with random-effects model; very low quality evidence, respectively). We found no study examining the effects of tDCS for improving activities of daily living. In two of six studies, dropouts , adverse events, or deaths occurring during the intervention phase were reported. There was insufficient evidence that dropouts , adverse effects, or deaths were higher with intervention (risk difference (RD) 0.04, 95% CI -0.05 to 0.12; P = 0.40, I\u00b2 = 0%, random-effects model; very low quality evidence). We found one trial with a total of 16 participants examining the effects of tDCS plus movement therapy compared to control (sham tDCS) plus movement therapy on our secondary outcome, gait speed at the end of the intervention phase, revealing no evidence of an effect (MD 0.05 m/s, 95% CI -0.15 to 0.25; inverse variance method with random-effects model; very low quality evidence). We found no evidence of an effect regarding differences in dropouts and adverse effects between intervention and control groups (RD 0.00, 95% CI -0.21 to 0.21; Mantel-Haenszel method with random-effects model; very low quality evidence). There is insufficient evidence to determine the effects of tDCS for reducing off time ( when the symptoms are not controlled by the medication) and on time with dyskinesia ( time that symptoms are controlled but the person still experiences involuntary muscle movements ) , and for improving health- related quality of life, disability, and impairment in patients with IPD. Evidence of very low quality indicates no difference in dropouts and adverse events between tDCS and control groups.",
        "gold": "We included six trials involving 137 participants. The duration of treatment in the included trials ranged from a single session to five consecutive sessions of tDCS. From the six trials involving 137 participants, we found there was insufficient evidence to determine how much of an effect there is from tDCS in enhancing rehabilitation outcomes regarding reduction in off time (when the symptoms are not controlled by the medication) and on time with dyskinesia (time that symptoms are controlled but the person still experiences involuntary muscle movements) , and for improving health- related quality of life, disability, and impairment in patients with IPD. However, tDCS may improve impairment regarding motor symptoms in patients with IPD. We found no study examining the effects of tDCS for improving activities of daily living. Proportions of adverse events and people discontinuing the study were comparable between groups. All findings are based on evidence of very low quality. That means that we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect."
    },
    {
        "index": "cochrane-simplification-test-324",
        "sentence": "We included an additional four studies (N = 154) in this update. For this update, we excluded studies that did not follow up patients for more than 48 hours. As a result, we excluded four studies from the previous review in this update. Overall we included 12 studies (N = 461), all of which we judged to be at high or unclear risk of bias. Overall, the quality of evidence was low to very low, downgraded due to limitations, inconsistency, imprecision, indirectness, or a combination of these. Two small studies compared LASB to placebo/sham (N = 32). They did not demonstrate significant short-term benefit for LASB for pain intensity (moderate quality evidence). One small study (N = 36) at high risk of bias compared thoracic sympathetic block with corticosteroid and local anaesthetic versus injection of the same agents into the subcutaneous space, reporting statistically significant and clinically important differences in pain intensity at one-year follow-up but not at short term follow-up (very low quality evidence). Of two studies that investigated LASB as an addition to rehabilitation treatment, the only study that reported pain outcomes demonstrated no additional benefit from LASB (very low quality evidence). Eight small randomised studies compared sympathetic blockade to various other active interventions. Most studies found no difference in pain outcomes between sympathetic block versus other active treatments (low to very low quality evidence). One small study compared ultrasound-guided LASB with non-guided LASB and found no clinically important difference in pain outcomes (very low quality evidence). Six studies reported adverse events, all with minor effects reported. This update's results are similar to the previous versions of this systematic review, and the main conclusions are unchanged. There remains a scarcity of published evidence and a lack of high quality evidence to support or refute the use of local anaesthetic sympathetic blockade for CRPS. From the existing evidence, it is not possible to draw firm conclusions regarding the efficacy or safety of this intervention, but the limited data available do not suggest that LASB is effective for reducing pain in CRPS.",
        "gold": "In September 2015, we found a limited number of small trials, all of which had design flaws. We did not find evidence that LASB was better than placebo in reducing pain, or that it provided additional pain relief when added to rehabilitation. While a number of small studies compared LASB to other treatments, most did not find that LASB was better. One small study found that injecting the thoracic (upper back) sympathetic nerves with local anaesthetic and steroid was better than injecting the same drugs just under the skin at one-year follow-up, but the study may have been prone to bias. Only six studies reported on the type and amount of side effects. These studies reported only minor side effects, but since some studies did not report this information we can draw no firm conclusions about the safety of LASB. The evidence was mostly of low or very low quality. Overall, the evidence is limited, conflicting, and of low quality. While we cannot draw strong conclusions, the existing evidence is not encouraging."
    },
    {
        "index": "cochrane-simplification-test-325",
        "sentence": "Fourteen trials, including 2488 participants, met the inclusion criteria. Most were small, and most were at high or unclear risk of bias in multiple domains. We included four new studies at this update. Incomplete recovery A combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in people with Bell's palsy compared to corticosteroids alone (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.38 to 1.74; 3 trials, N = 766; random-effects; low-certainty evidence). We excluded 10 trials that were at high or unclear risk of bias in several domains from this analysis and limited all analyses to studies at lower risk of bias. Recovery rates were better in participants receiving corticosteroids alone than antivirals alone (RR 2.69, 95% CI 0.73 to 10.01; 2 trials, N = 667; random-effects), but the result was imprecise and allowed for the possibility of no effect. The rate of incomplete recovery was lower with antivirals plus corticosteroids than with placebo or no treatment (RR 0.56, 95% CI 0.42 to 0.76; 2 trials, N = 658; random-effects). Antivirals alone had no clear effect on incomplete recovery rates compared with placebo, but the result was imprecise (RR 1.10, 95% CI 0.87 to 1.40; 2 trials, N = 658; fixed-effect). For people with severe Bell's palsy (House-Brackmann score of 5 and 6, or equivalent on other scales), we found that the combination of antivirals and corticosteroids had no clear effect on incomplete recovery at month six compared to corticosteroids alone, although the result was again imprecise (RR 0.82, 95% CI 0.57 to 1.17; 2 trials, N = 98; random-effects). Motor synkinesis or crocodile tears Antivirals plus corticosteroids reduced the proportion of participants who experienced these long-term sequelae from Bell's palsy compared to placebo plus corticosteroids (RR 0.56, 95% CI 0.36 to 0.87; 2 trials, N = 469; fixed-effect; moderate-certainty evidence). Antivirals plus corticosteroids reduced long-term sequelae compared to placebo but there was no clear difference in this outcome with antivirals alone compared to placebo. Adverse events Adverse event data were available in four studies providing data on 1592 participants. None of the four comparisons showed clear differences in adverse events between treatment and comparison arms (very low-certainty evidence); for the comparison of antivirals plus corticosteroids and corticosteroids alone in studies at lower risk of bias, the RR was 1.17 (95% CI 0.81 to 1.69; 2 trials, N = 656; fixed-effect; very low-certainty evidence). The combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in comparison to corticosteroids alone in Bell's palsy of various degrees of severity, or in people with severe Bell's palsy, but the results were very imprecise. Corticosteroids alone were probably more effective than antivirals alone and antivirals plus corticosteroids were more effective than placebo or no treatment. There was no clear benefit from antivirals alone over placebo. The combination of antivirals and corticosteroids probably reduced the late sequelae of Bell's palsy compared with corticosteroids alone. Studies also showed fewer episodes of long-term sequelae in corticosteroid-treated participants than antiviral-treated participants. We found no clear difference in adverse events from the use of antivirals compared with either placebo or corticosteroids, but the evidence is too uncertain for us to draw conclusions. An adequately powered RCT in people with Bell\u2019s palsy that compares different antiviral agents may be indicated.",
        "gold": "We identified 14 trials, which included 2488 participants with mild, moderate, or severe one-sided Bell's palsy of unknown cause. Participants were aged from 14 to 84 years. The trials compared: - antivirals plus corticosteroids to corticosteroids alone or in combination with placebo; - antivirals alone or in combination with placebo to placebo or no treatment; - antivirals alone or in combination with placebo to corticosteroid treatment alone or in combination with placebo; or - antivirals plus corticosteroids to placebo or no treatment. For the majority of the studies, no information on funding was given. The remaining were mostly partly public funded, and one trial was funded by a pharmaceutical company. Eleven studies had high or uncertain risk of bias from various factors that can systematically affect trial results. We chose to base our conclusions only on data from three studies at a lower risk of bias. The review showed that there may be no clear difference in rates of incomplete recovery from Bell's palsy after treatment with the combination of antivirals and corticosteroids, compared to corticosteroids alone. This finding was of low certainty and was based on data from three trials involving 766 people with Bell's palsy of various degrees of severity. We excluded data from 10 trials with multiple potential sources of bias. However, we can be moderately confident that the combined therapy reduced the number of people left with long-term effects of Bell's palsy (excessive tearing of the eyes or an abnormal facial movement) compared to corticosteroid treatment alone. Data from two studies (98 participants) showed that in people with severe Bell's palsy (complete or almost complete facial paralysis), combined antivirals and corticosteroids had no clear effect on recovery compared with corticosteroid treatment alone. Corticosteroids alone were more effective than antivirals alone on rates of incomplete recovery (667 participants, 2 trials); antivirals and corticosteroids combined were more effective than placebo or no treatment (658 participants, 2 trials); and there was no clear benefit from antivirals alone over placebo (658 participants, 2 trials). Although, based on data from two trials (656 participants), we found no clear difference in the occurrence of side effects between people receiving both antivirals and corticosteroids, compared to those receiving corticosteroids alone, this evidence is too uncertain for us to draw conclusions. Large studies in people with Bell's palsy comparing additional antiviral agents may be indicated in the future."
    },
    {
        "index": "cochrane-simplification-test-326",
        "sentence": "Two studies, including 97 women, met our inclusion criteria: one assessed LHRH agonist (leuprorelin) use in relapsed (platinum-resistant and platinum-refractory) EOC in comparison with a chemotherapeutic agent (treosulfan) (Du Bois 2002); the other examined LHRH agonist (decapeptyl) versus a placebo (Currie 1994). Since both studies had different control groups, a meta-analysis was not possible. There may be little or no difference between treatment with leuprorelin or treosulfan in overall survival (OS) (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.58 to 1.67; very low-quality evidence) or progression-free survival (PFS) at six and 12 months (risk ratio (RR) 0.61, 95% CI 0.22 to 1.68, and RR 0.65, 95% CI 0.12 to 3.66; very low-quality evidence), respectively (Du Bois 2002). The duration of follow-up was 2.5 years and quality of life (QoL) was not reported in this study. Alopecia and fatigue were probably more common with treosulfan than leuprorelin (alopecia RR 0.32, 95% CI 0.12 to 0.91 (very low-quality evidence)). There may be little or no difference in other Grade 3/4 side effects: nausea and vomiting (RR 0.65, 95% CI 0.12 to 3.66 (very low-quality evidence)); neurotoxicity (RR 0.32, 95% CI 0.01 to 7.71 (very low-quality evidence)) and neutropenia (RR 0.97, 95% 0.06 to 14.97 (very low-quality evidence)), The Currie 1994 study, which compared decapeptyl treatment with placebo, reported mean PFS of 16 weeks verus 11.2 weeks, respectively. No relative effects measures or P value at a particular time point were reported. Overall survival (OS) and QoL outcomes were not reported. In addition, adverse events were only mentioned for the decapeptyl group. Adverse events were incompletely reported (no adverse events in decapeptyl group, but not reported for the placebo group). Based on this review of two small RCTs, there is not enough evidence to comment on the safety and effectiveness of LHRH agonists in the treatment of platinum-refractory and platinum-resistant (relapsed) EOC. Overall, the quality of evidence for all outcomes (including OS, PFS, QoL and adverse events) is very low.",
        "gold": "We searched electronic databases and other resources for randomised controlled trials (RCTs) comparing LHRH agonists with chemotherapy or placebo in women with relapsed EOC.Two RCTs were identified. Since the comparisons differed, they were reported separately. Available evidence did not show improvement in overall survival and progression-free survival at six and12 months with hormonal (LHRH) therapy. Also, major side effects (haematological and neurological) did not statistically differ between the two treatment groups, but were incompletely reported. Quality of life data were not reported in either study. Currently, the quality of evidence is very low regarding the effectiveness and safety of LHRH agonists in women who relapse within six months of initial platinum chemotherapy treatment."
    },
    {
        "index": "cochrane-simplification-test-327",
        "sentence": "We found 17 eligible randomised controlled studies that included term and near-term infants with hypoxia. Ten trials compared iNO versus control (placebo or standard care without iNO) in infants with moderate or severe severity of illness scores (Ninos 1996; Roberts 1996; Wessel 1996; Davidson 1997; Ninos 1997; Mercier 1998; Christou 2000; Clark 2000; INNOVO 2007; Liu 2008). Mercier 1998 compared iNO versus control but allowed back-up treatment with iNO for infants who continued to satisfy the same criteria for severity of illness after two hours. This trial enrolled both preterm and term infants but reported most results separately for the two groups. Ninos 1997 studied only infants with congenital diaphragmatic hernia. One trial compared iNO versus high-frequency ventilation (Kinsella 1997). Six trials enrolled infants with moderate severity of illness scores (oxygenation index (OI) or alveolar-arterial oxygen difference (A-aDO2)) and randomised them to immediate iNO treatment or iNO treatment only after deterioration to more severe criteria (Barefield 1996; Day 1996; Sadiq 1998; Cornfield 1999; Konduri 2004; Gonzalez 2010). Inhaled nitric oxide appears to have improved outcomes in hypoxaemic term and near-term infants by reducing the incidence of the combined endpoint of death or use of ECMO (high-quality evidence). This reduction was due to a reduction in use of ECMO (with number needed to treat for an additional beneficial outcome (NNTB) of 5.3); mortality was not affected. Oxygenation was improved in approximately 50% of infants receiving iNO. The OI was decreased by a (weighted) mean of 15.1 within 30 to 60 minutes after the start of therapy, and partial pressure of arterial oxygen (PaO2) was increased by a mean of 53 mmHg. Whether infants had clear echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN) did not appear to affect response to iNO. Outcomes of infants with diaphragmatic hernia were not improved; outcomes were slightly, but not significantly, worse with iNO (moderate-quality evidence). Infants who received iNO at less severe criteria did not have better clinical outcomes than those who were enrolled but received treatment only if their condition deteriorated. Fewer of the babies who received iNO early satisfied late treatment criteria, showing that earlier iNO reduced progression of the disease but did not further decrease mortality nor the need for ECMO (moderate-quality evidence). Incidence of disability, incidence of deafness and infant development scores were all similar between tested survivors who received iNO and those who did not. Inhaled nitric oxide is effective at an initial concentration of 20 ppm for term and near-term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia.",
        "gold": "In a search updated to February 2016, review authors identified a total of 17 studies for inclusion in the review. Most of the results reported in this review were obtained from 10 studies of moderate to high quality, which compared inhaled nitric oxide (iNO) versus standard therapy without iNO. Six studies compared iNO started when babies were less sick against waiting to see if they deteriorated, then treating them later. These studies were smaller, and only one was a high-quality trial. Inhaled nitric oxide is safe and can help some full-term babies with respiratory failure who have not responded to other methods of support. Inhaled nitric oxide increases levels of oxygen in babies' blood, and babies are more likely to survive without needing ECMO, a highly invasive therapy with many complications. Unfortunately, benefits of iNO are not clear in babies whose respiratory failure is due to a diaphragmatic hernia. Inhaled nitric oxide has shown no short-term or long-term adverse effects. No signs suggest that iNO given earlier is more beneficial or results in more babies treated, and the number who die or who need ECMO is not significantly reduced."
    },
    {
        "index": "cochrane-simplification-test-328",
        "sentence": "Seven preventive studies (14,437 people) and eight treatment studies (1361 people) were included in this updated review. Overall, the methodological quality of the studies was rather low. Only five of the fifteen studies met 50% or more of the internal validity items. There was moderate evidence that lumbar supports are not more effective than no intervention or training in preventing low-back pain, and conflicting evidence whether lumbar supports are effective supplements to other preventive interventions. It is still unclear if lumbar supports are more effective than no or other interventions for the treatment of low-back pain. There is moderate evidence that lumbar supports are not more effective than no intervention or training in preventing low-back pain, and conflicting evidence whether they are effective supplements to other preventive interventions. It remains unclear whether lumbar supports are more effective than no or other interventions for treating low-back pain. There is still a need for high quality randomised trials on the effectiveness of lumbar supports. One of the most essential issues to tackle in these future trials seems to be the realization of an adequate compliance. Special attention should be paid to different outcome measures, types of patients and types of lumbar support.",
        "gold": "In one study (82 people), back supports added to back school (patient education about recovering from back pain) were helpful in reducing the number of days of sick leave but not in preventing back pain. Back supports plus usual medical care reduced the number of days of low-back pain and improved function, but did not reduce sick leave (one study, 360 people). Treatment:  In four studies (1170 people), there was little or no difference between patients with acute or chronic back pain who used back supports and those who received no treatment in short-term pain reduction or overall improvement. There is conflicting evidence (two studies, 550 people) about whether back supports are better than nothing in helping low-back pain patients return to work faster, however in three studies (410 patients), they were better than nothing in helping individuals with subacute and chronic low-back pain recover function in the short term. In three studies (954 people), there was little or no difference in short-term pain reduction, overall improvement and return-to-work between those who used back supports and those who received manipulation, physiotherapy, or electrical stimulation. One study (164 people) reported mixed results on whether back supports improved function more than massage and in another study (19 people), use of a lumbar corset with back support was more effective in reducing pain in the short-term than a corset alone. Conclusions from this review should be viewed with caution due to the low quality of many of the studies. In the future, researchers should report side effects from wearing back supports and measure how many hours per day the supports are actually worn."
    },
    {
        "index": "cochrane-simplification-test-329",
        "sentence": "We included one new study (338 participants/catheters) in this update, which brought the total included to 57 studies with 16,784 catheters and 11 types of impregnations. The total number of participants enrolled was unclear, as some studies did not provide this information. Most studies enrolled participants from the age of 18, including patients in intensive care units (ICU), oncology units and patients receiving long-term total parenteral nutrition. There were low or unclear risks of bias in the included studies, except for blinding, which was impossible in most studies due to the catheters that were being assessed having different appearances. Overall, catheter impregnation significantly reduced catheter-related blood stream infection (CRBSI), with an ARR of 2% (95% CI 3% to 1%), RR of 0.62 (95% CI 0.52 to 0.74) and NNTB of 50 (high-quality evidence). Catheter impregnation also reduced catheter colonization, with an ARR of 9% (95% CI 12% to 7%), RR of 0.67 (95% CI 0.59 to 0.76) and NNTB of 11 (moderate-quality evidence, downgraded due to substantial heterogeneity). However, catheter impregnation made no significant difference to the rates of clinically diagnosed sepsis (RR 1.0, 95% CI 0.88 to 1.13; moderate-quality evidence, downgraded due to a suspicion of publication bias), all-cause mortality (RR 0.92, 95% CI 0.80 to 1.07; high-quality evidence) and catheter-related local infections (RR 0.84, 95% CI 0.66 to 1.07; 2688 catheters, moderate quality evidence, downgraded due to wide 95% CI). In our subgroup analyses, we found that the magnitudes of benefits for impregnated CVCs varied between studies that enrolled different types of participants. For the outcome of catheter colonization, catheter impregnation conferred significant benefit in studies conducted in ICUs (RR 0.70;95% CI 0.61 to 0.80) but not in studies conducted in haematological and oncological units (RR 0.75; 95% CI 0.51 to 1.11) or studies that assessed predominantly patients who required CVCs for long-term total parenteral nutrition (RR 0.99; 95% CI 0.74 to 1.34). However, there was no such variation for the outcome of CRBSI. The magnitude of the effects was also not affected by the participants' baseline risks. There were no significant differences between the impregnated and non-impregnated groups in the rates of adverse effects, including thrombosis/thrombophlebitis, bleeding, erythema and/or tenderness at the insertion site. This review confirms the effectiveness of antimicrobial CVCs in reducing rates of CRBSI and catheter colonization. However, the magnitude of benefits regarding catheter colonization varied according to setting, with significant benefits only in studies conducted in ICUs. A comparatively smaller body of evidence suggests that antimicrobial CVCs do not appear to reduce clinically diagnosed sepsis or mortality significantly. Our findings call for caution in routinely recommending the use of antimicrobial-impregnated CVCs across all settings. Further randomized controlled trials assessing antimicrobial CVCs should include important clinical outcomes like the overall rates of sepsis and mortality.",
        "gold": "We included 57 studies with 16,784 catheters and 11 types of antimicrobial impregnation. The total number of participants was not clear as some studies did not provide this information, and some participants may have had more than one CVC in the course of their treatment. The participants were mostly adults aged 18 and over in ICUs, cancer units or other healthcare settings in which CVCs were used for intravenous treatment or nutrition. All studies were completed when the participants left the unit or hospital, and no study followed up participants in the long-term. Twenty-six out of 57 studies were funded fully or partially by the catheter manufacturers or distributors, two studies were government-funded, and two received no funding. Funding sources were not stated in the remaining 27 studies. Compared to those participants given non-impregnated catheters, participants with impregnated catheters had 2% lower rates of bloodstream infections that were definitely catheter-related (CRBSI) (average absolute reduction in CRBSI: 2%). There was also a 9% lower chance of finding bacteria on these impregnated catheters (catheter colonization) (average absolute reduction in catheter colonization: 9%). However, the benefits of these catheters in reducing catheter colonization varied according to study setting, with significant benefits observed only in studies conducted in the ICUs. There were no clinically significant differences in the overall rates of bloodstream infections (clinically-diagnosed sepsis) or in death, although these outcomes were assessed in fewer studies than CRBSI and catheter colonization. Impregnated catheters appeared no more likely than non-impregnated catheters to cause adverse effects such as bleeding, clots, pain or redness at the insertion site. The amount of information in this review contributed to high-quality evidence for the major outcomes of CRBSI, all-cause mortality and adverse effects. However, for clinically-diagnosed sepsis we considered the quality of the evidence to be moderate, as we suspected that there had been selective non-publication of certain trials. We considered the quality of evidence to be moderate for catheter colonization too, due to major inconsistencies in the direction of the results amongst the included studies. While impregnated catheters are effective in reducing CRBSI and catheter colonization, particularly in ICUs, they may not be effective across all settings. Furthermore, our review shows that these impregnated catheters do not appear to reduce all bloodstream infections and numbers of deaths. The discrepancy between the findings for CRBSI, catheter colonization and overall bloodstream infections might be related to the limitations of the catheter and blood cultures that were used in most studies for detecting catheter-related infections. Future research should include overall bloodstream infections and death as key outcomes, and include some advanced methods for detecting micro-organisms on the catheters and in the bloodstream to evaluate the presence of catheter-related infections more accurately."
    },
    {
        "index": "cochrane-simplification-test-330",
        "sentence": "The systematic review included 15 studies, of which 14 were randomised controlled trials (RCTs). The interventions took place in recognised slums or poor urban or periurban areas. The study locations were mainly Bangladesh, India, and Peru. The participants included 9261 infants and children and 3664 pregnant women. There were no dietary intervention studies. All the studies identified were nutrient supplementation and educational interventions. The interventions included zinc supplementation in pregnant women (three studies), micronutrient or macronutrient supplementation in children (eight studies), nutrition education for pregnant women (two studies), and nutrition systems strengthening targeting children (two studies) intervention. Six interventions were adapted to the urban context and seven targeted household, community, or 'service delivery' via systems strengthening. The primary review outcomes were available from seven studies for LFA/HFA, four for LBW, and nine for length. The studies had overall high risk of bias for 11 studies and only four RCTs had moderate risk of bias. Overall, the evidence was complex to report, with a wide range of outcome measures reported. Consequently, only eight study findings were reported in meta-analyses and seven in a narrative form. The certainty of evidence was very low to moderate overall. None of the studies reported differential impacts of interventions relevant to equity issues. Zinc supplementation of pregnant women on LBW or length (versus supplementation without zinc or placebo) (three RCTs) There was no evidence of an effect on LBW (MD \u201336.13 g, 95% CI \u201383.61 to 11.35), with moderate-certainty evidence, or no evidence of an effect or unclear effect on length with low- to moderate-certainty evidence. Micronutrient or macronutrient supplementation in children (versus no intervention or placebo) (eight RCTs) There was no evidence of an effect or unclear effect of nutrient supplementation of children on HFA for studies in the meta-analysis with low-certainty evidence (MD \u20130.02, 95% CI \u20130.06 to 0.02), and inconclusive effect on length for studies reported in a narrative form with very low- to moderate-certainty evidence. Nutrition education for pregnant women (versus standard care or no intervention) (two RCTs) There was a positive impact on LBW of education interventions in pregnant women, with low-certainty evidence (MD 478.44g, 95% CI 423.55 to 533.32). Nutrition systems strengthening interventions targeting children (compared with no intervention, standard care) (one RCT and one controlled before-and-after study) There were inconclusive results on HFA, with very low- to low-certainty evidence, and a positive influence on length at 18 months, with low-certainty evidence. All the nutritional interventions reviewed had the potential to decrease stunting, based on evidence from outside of slum contexts; however, there was no evidence of an effect of the interventions included in this review (very low- to moderate-certainty evidence). Challenges linked to urban slum programming (high mobility, lack of social services, and high loss of follow-up) should be taken into account when nutrition-specific interventions are proposed to address LBW and stunting in such environments. More evidence is needed of the effects of multi-sectorial interventions, combining nutrition-specific and sensitive methods and programmes, as well as the effects of 'up-stream' practices and policies of governmental, non-governmental organisations, and the business sector on nutrition-related outcomes such as stunting.",
        "gold": "Nutritional methods (interventions) to improve infant and young children's growth have not been comprehensively or systematically assessed for urban slums. We included 15 studies in the review, involving 9261 children less than five years old and 3664 pregnant women. About 73% of children were less than one year old. The interventions provided maternal education; nutrient supplementation of mothers, infants, and children; improving nutrition systems; or a combination of these but not dietary modification. The reliability of the studies was very low to moderate overall because studies were not designed to cope with research problems linked to urban slum communities, such as high mobility and high loss of participants to follow-up. This meant that the effectiveness of the intervention could not be properly assessed at later dates. We assessed the effect of interventions taking both statistical and clinical significance into account. Where intervention outcomes were statistically insignificant, we conclude there was 'unclear effect'. There was no effect of giving mothers nutrient supplementation on birth weight and length, there were inconclusive results for nutrient supplementation in infants and children on improving children's height or stunting status, there was a positive impact on birth weight of maternal education interventions where there was a positive difference in birth weight of 478 g in infants exposed to the intervention, and inconclusive results of improving health systems that support nutrition on children's stunting status and a positive effect on height. There were no reported side effects from these interventions. The review showed the need to better understand urban slum environments and their people as evidence showed that interventions included in this review were successful in other locations outside of urban poor areas. More evidence is needed of the effects of multi-sectorial interventions, combining nutrition-specific and sensitive methods and programmes, as well as the effects of 'up-stream' practices and policies of governmental, non-governmental organisations (NGOs), and the business sector to improve low birth weight and stunting in poor urban environments."
    },
    {
        "index": "cochrane-simplification-test-331",
        "sentence": "Twelve RCTs (1023 participants) reporting 14 comparisons were included in this review. There was no difference in healing outcomes between hydrocellular foam dressings and polyurethane foam dressings (three RCTs). Pooled data across five RCTs (418 participants) showed no statistically significant difference between foam dressings and hydrocolloid dressings in the proportion of ulcers healed at 12 to 16 weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.81 to 1.22). No statistically significant between-group differences in healing outcomes were detected when foam dressings were compared with: paraffin gauze (two RCTs); hydrocapillary dressing (one RCT); knitted viscose dressing (one RCT); and protease modulating matrix (one RCT). No statistically significant between-group differences in the proportion of participants experiencing adverse events were detected when hydrocellular foam dressings were compared with polyurethane foam dressings, or when foam dressings were compared with hydrocapillary, hydrocolloid, or knitted viscose dressings (one RCT for each comparison). Six RCTs were considered as being at overall high risk of bias, and the remaining six RCTs were considered to be at overall unclear risk of bias. No included RCT had an overall low risk of bias. The current evidence base does not suggest that foam dressings are more effective in the healing of venous leg ulcers than other wound dressing treatments. The evidence in this area is of low quality.\u00a0Further evidence is required from well-designed and rigorously-conducted RCTs, that employ methods to minimise bias and report them clearly, before any definitive conclusions can be made regarding the efficacy of foam dressings in the management of venous leg ulcers.",
        "gold": "We evaluated the evidence from 12 randomised controlled trials that either compared different types of foam dressings, or compared foam dressings with other types of wound dressings. We found no evidence to suggest that polyurethane foam dressings are significantly better or worse than hydrocellular foam dressings in venous leg ulcer healing. Similarly, we found no evidence to suggest that foam dressings are significantly better or worse than other types of dressings (paraffin-impregnated gauze dressings, hydrocapillary dressings, hydrocolloid dressings, knitted viscose dressings, or protease-modulating matrix dressings), for the healing of venous leg ulcers. We found insufficient evidence to draw any conclusions regarding: adverse events, quality of life, costs, pain, or dressing performance. Overall, the current evidence is of low or unclear methodological quality. This limits the making of any specific recommendations regarding the use of foam dressings. Further, good quality evidence is required before definitive conclusions can be made regarding the role of foam dressings in the management of venous leg ulcers."
    },
    {
        "index": "cochrane-simplification-test-332",
        "sentence": "There were no RCTs that assessed the tolerability or safety of the withdrawn COX-2 inhibitors rofecoxib, valdecoxib, or lumiracoxib. Two RCTs (n = 381 IBD patients with rheumatological manifestations) were included in the review. One study (n = 159) compared etoricoxib (60 to 120 mg/day) to placebo in IBD patients with quiescent or active ulcerative colitis or Crohn's disease. The other study (n = 222) compared celecoxib (200 mg twice daily) to placebo in patients with quiescent ulcerative colitis. Both studies were judged to be at low risk of bias. The two included studies were not pooled for meta-analysis due to differences in patient populations and treatment duration. There was no statistically significant difference in exacerbation of IBD between etoricoxib and placebo. After 12 weeks of treatment the IBD exacerbation rate was 17% (14/82) in the etoricoxib group compared to 19% (15/77) in the placebo group (RR 0.88, 95% CI 0.45 to 1.69). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (29 events). There was no statistically significant difference in exacerbation of ulcerative colitis between celecoxib and placebo. After two weeks of treatment 4% (5/112) of celecoxib patients experienced an exacerbation of ulcerative colitis compared to 6% (7/110) of patients in the placebo group (RR 0.70, 95% CI 0.23 to 2.14). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (12 events). The study comparing etoricoxib to placebo documented but did not report on AEs. The proportion of patients who experienced AEs was similar in the celecoxib and placebo groups (21% and 17%, respectively, P > 0.20). No patients in either group died or experienced serious adverse events. Eleven percent of patients in the celecoxib and placebo groups experienced GI AEs (RR 0.97, 95% CI 0.46 to 2.07). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (24 events). GI AEs led to premature withdrawal from the study in 3% of patients in celecoxib and placebo groups respectively. GI AEs included increased stool frequency, rectal bleeding, and inflamed mucosa. No patients experienced any cardiovascular adverse events. Renal toxicity or thrombotic AEs were not reported. The results for disease exacerbation and AEs between the COX-2 inhibitors celecoxib and etoricoxib and placebo were uncertain. Thus no definitive conclusions regarding the tolerability and safety of the short term use of celecoxib and etoricoxib in patients with IBD can be drawn. The two included studies suggest that celecoxib and etoricoxib do not exacerbate IBD symptoms. However, it should be noted that both studies had relatively small sample sizes and short follow-up durations. Clinicians need to continue to weigh the risks and benefits of these drugs when treating patients IBD patients with rheumatological manifestations in order to avoid disease exacerbation and other adverse effects. Further RCTs are needed to determine the tolerability and safety of celecoxib and etoricoxib in these patients.",
        "gold": "This review does not include any studies that assessed the tolerability and safety of the withdrawn COX-2 inhibitors rofecoxib, valdecoxib, or lumiracoxib.This review identified two studies that included a total of 381 participants with IBD who were experiencing rheumatological manifestations. One study (159 participants) compared etoricoxib (60 to 120 mg/day) to placebo (e.g. a sugar pill) in people with IBD (ulcerative colitis or Crohn's disease) who were in remission (i.e. no disease symptoms) or had active disease (i.e. had symptoms). The other study (222 participants) compared 2 weeks of treatment with celecoxib (200 mg twice daily) to placebo in people with ulcerative colitis who were in remission. The study that compared etoricoxib to placebo found no clear evidence of a difference in the proportion of patients who experienced exacerbation of IBD after 12 weeks of treatment. Although this study documented side effects experienced by the participants these side effects were not reported in the study manuscript. The study that compared celecoxib to placebo found no clear evidence of a difference in the proportion of patients who experienced exacerbation of ulcerative colitis after two weeks of treatment. The proportion of patients who experienced side effects was similar in the celecoxib and placebo groups (21% and 17%, respectively). No patients in either group died or experienced serious side effects. Eleven percent of patients in the celecoxib and placebo groups experienced GI side effects including increased stool frequency, rectal bleeding, and inflamed mucosa. No patients experienced any cardiovascular side effects (i.e. heart attack or stroke). Renal toxicity (i.e. the poisonous effect of a substance on the kidneys) or thrombotic side effects (i.e. the formation of a blood clot inside a blood vessel) were not reported. The results of the two included studies in this review suggest that celecoxib and etoricoxib do not exacerbate IBD symptoms. However, it should be noted that both studies assessed relatively small numbers of patients and were of short duration. Futhermore, the overall quality of the evidence from the studies was rated as low due to lack of precision of the results. No firm conclusions on the tolerability and safety of celecoxib and etoricoxib can be drawn from these studies. Further studies are needed to determine the tolerability and safety of celecoxib and etoricoxib in patients with rheumatological manifestations of inflammatory bowel disease."
    },
    {
        "index": "cochrane-simplification-test-333",
        "sentence": "We found 22 trials that met our inclusion criteria with a total of over 2310 participants (one study did not report number of participants). The included studies mostly had small numbers of participants (from 4 to 317) and relatively short follow-up periods (4 to 24 weeks). At baseline, six trials included only people with ulcers that were clinically infected; one trial included people with both infected and uninfected ulcers; two trials included people with non-infected ulcers; and the remaining 13 studies did not report infection status. Included studies employed various topical antimicrobial treatments, including antimicrobial dressings (e.g. silver, iodides), super-oxidised aqueous solutions, zinc hyaluronate, silver sulphadiazine, tretinoin, pexiganan cream, and chloramine. We performed the following five comparisons based on the included studies: Antimicrobial dressings compared with non-antimicrobial dressings: Pooled data from five trials with a total of 945 participants suggest (based on the average treatment effect from a random-effects model) that more wounds may heal when treated with an antimicrobial dressing than with a non-antimicrobial dressing: risk ratio (RR) 1.28, 95% confidence interval (CI) 1.12 to 1.45. These results correspond to an additional 119 healing events in the antimicrobial-dressing arm per 1000 participants (95% CI 51 to 191 more). We consider this low-certainty evidence (downgraded twice due to risk of bias). The evidence on adverse events or other outcomes was uncertain (very low-certainty evidence, frequently downgraded due to risk of bias and imprecision). Antimicrobial topical treatments (non dressings) compared with non-antimicrobial topical treatments (non dressings): There were four trials with a total of 132 participants in this comparison that contributed variously to the estimates of outcome data. Evidence was generally of low or very low certainty, and the 95% CIs spanned benefit and harm: proportion of wounds healed RR 2.82 (95% CI 0.56 to 14.23; 112 participants; 3 trials; very low-certainty evidence); achieving resolution of infection RR 1.16 (95% CI 0.54 to 2.51; 40 participants; 1 trial; low-certainty evidence); undergoing surgical resection RR 1.67 (95% CI 0.47 to 5.90; 40 participants; 1 trial; low-certainty evidence); and sustaining an adverse event (no events in either arm; 81 participants; 2 trials; very low-certainty evidence). Comparison of different topical antimicrobial treatments: We included eight studies with a total of 250 participants, but all of the comparisons were different and no data could be appropriately pooled. Reported outcome data were limited and we are uncertain about the relative effects of antimicrobial topical agents for each of our review outcomes for this comparison, that is wound healing, resolution of infection, surgical resection, and adverse events (all very low-certainty evidence). Topical antimicrobials compared with systemic antibiotics : We included four studies with a total of 937 participants. These studies reported no wound-healing data, and the evidence was uncertain for the relative effects on resolution of infection in infected ulcers and surgical resection (very low certainty). On average, there is probably little difference in the risk of adverse events between the compared topical antimicrobial and systemic antibiotics treatments: RR 0.91 (95% CI 0.78 to 1.06; moderate-certainty evidence - downgraded once for inconsistency). Topical antimicrobial agents compared with growth factor: We included one study with 40 participants. The only review-relevant outcome reported was number of ulcers healed, and these data were uncertain (very low-certainty evidence). The randomised controlled trial data on the effectiveness and safety of topical antimicrobial treatments for diabetic foot ulcers is limited by the availability of relatively few, mostly small, and often poorly designed trials. Based on our systematic review and analysis of the literature, we suggest that: 1) use of an antimicrobial dressing instead of a non-antimicrobial dressing may increase the number of diabetic foot ulcers healed over a medium-term follow-up period (low-certainty evidence); and 2) there is probably little difference in the risk of adverse events related to treatment between systemic antibiotics and topical antimicrobial treatments based on the available studies (moderate-certainty evidence). For each of the other outcomes we examined there were either no reported data or the available data left us uncertain as to whether or not there were any differences between the compared treatments. Given the high, and increasing, frequency of diabetic foot wounds, we encourage investigators to undertake properly designed randomised controlled trials in this area to evaluate the effects of topical antimicrobial treatments for both the prevention and the treatment of infection in these wounds and ultimately the effects on wound healing.",
        "gold": "In August 2016 we searched for randomised controlled trials involving the use of any antimicrobial treatment on foot ulcers or other open wounds of the foot in people with diabetes. We found 22 trials involving a total of over 2310 adult participants (one trial did not report the number of participants). Participant numbers in each trial ranged from 4 to 317 and follow-up times during and after treatment ranged from 4 to 24 weeks. Some trials included participants with ulcers that were infected, while other trials included participants with ulcers that were uninfected. The trials compared a variety of different antimicrobial dressings, solutions, gels, creams, or ointments. Many of the trials did not report important data, which means the reliability of the results is uncertain. The results of five trials involving 945 participants suggest that use of some type of antimicrobial dressing may increase the number of ulcers healed in medium-term follow-up (4 to 24 weeks) when compared with a non-antimicrobial dressing (low certainty evidence). Due to limited information, we were unable to assess the effectiveness of treatments in either preventing or resolving wound infection. Four trials involving 937 participants compared systemic antibiotics (given by mouth or via injection, distributed to the whole body by the bloodstream) with antimicrobial treatments applied directly to the wound. These trials did not provide data on healing or infection, but it appeared that there was no difference in the side effects experienced by participants whose ulcers were treated systemically or topically (moderate certainty evidence). Overall, the certainty of the evidence provided by the trials was too low for us to be certain of the benefits and harms of topical antimicrobial treatments for treating foot ulcers in people with diabetes. More, larger, and better-designed randomised controlled trials should be carried out in this area."
    },
    {
        "index": "cochrane-simplification-test-334",
        "sentence": "We did not identify any new studies for inclusion in this update. We included six studies that involved 5193 participants. Analysis showed that zinc supplementation reduced the incidence of pneumonia by 13% (fixed-effect risk ratio (RR) 0.87; 95% confidence interval (CI) 0.81 to 0.94, six studies, low-quality evidence) and prevalence of pneumonia by 41% (random-effects RR 0.59; 95% CI 0.35 to 0.99, one study, n = 609, low-quality evidence). On subgroup analysis, we found that zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21% (i.e. confirmation by chest examination or chest radiograph) (fixed-effect RR 0.79; 95% CI 0.71 to 0.88, four studies, n = 3261), but had no effect on lower specificity pneumonia case definition (i.e. age-specific fast breathing with or without lower chest indrawing) (fixed-effect RR 0.95; 95% CI 0.86 to 1.06, four studies, n = 1932). Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia.",
        "gold": "We included six studies that investigated zinc supplements to prevent pneumonia. The studies were conducted in Bangladesh, India, Peru and South Africa and involved 5193 children aged from two to 59 months. Children received either zinc or a similar-looking treatment that did not contain zinc. In two studies, children were also given vitamin A. All included studies were funded. Of these, three explicitly mentioned that funding agencies had no role in the design and results of the study. Zinc supplementation was significantly associated with reducing the incidence and prevalence of pneumonia among children aged from two to 59 months. On subgroup analysis, we found that a more stringent diagnosis (radiological examination) increased the reduction in pneumonia incidence. Overall, evidence quality was assessed as low on GRADE assessment."
    },
    {
        "index": "cochrane-simplification-test-335",
        "sentence": "Ten studies including 33,179 participants were included in this review. Eight studies found no significant effect of vitamin A on the incidence of acute LRTI, or prevalence of symptoms of acute LRTI. Vitamin A caused an increased incidence of acute LRTI in one study; an increase in cough and fever; and increased symptoms of cough and rapid breathing in two other studies. Three reported no differences and no protective effect of vitamin A. Two studies reported that vitamin A significantly reduced the incidence of acute LRTI in children with poor nutritional status or weight, but increased the incidence in healthy children. This unexpected result is outside our current understanding of the use of vitamin A for preventing acute LRTIs. Accordingly, vitamin A should not be given to all children to prevent acute LRTIs. Despite its benefits in preventing diarrhoeal illnesses, vitamin A supplementation has only a limited effect in preventing acute LRTIs. Positive effects appear limited to populations with acute and chronic under nutrition. Low-dose vitamin A appears to have fewer side effects and at least equal benefit to a high dose of vitamin A.",
        "gold": "We included 10 trials (33,179 children) where vitamin A deficiency or malnutrition was prevalent (31,379 in the community and 1800 in a hospital setting). Studies measured different aspects (for example, what constituted 'acute LRTI', the time to symptom resolution, etc.). There may have been other treatments (especially of malnourished children) which could have led to bias. Most studies showed no significant benefit of vitamin A supplements on the incidence or prevalence of symptoms of acute LRTIs. Although no included studies addressed adverse effects of vitamin A, the use of vitamin A should be carefully monitored. We do not recommend giving vitamin A to all children to prevent acute LRTIs because a few studies unexpectedly found that vitamin A increased the chance of infections or worsened symptoms in otherwise healthy children. Some evidence shows benefit for vitamin supplements given to children with low serum retinol or with a poor nutritional status. Limitations of our review include trials conducted within very specific populations and poor methodological quality of some of the included trials."
    },
    {
        "index": "cochrane-simplification-test-336",
        "sentence": "Twenty RCTs met the inclusion criteria. Concomitant therapy varied from none to any other bronchodilator plus corticosteroid (oral and inhaled). The following outcomes were significantly different when compared to placebo. Forced expiratory volume in one second (FEV1) improved with treatment: Weighted Mean Difference (WMD) 100 ml; 95% Confidence Interval (CI) 40 to 160 ml. Similarly for forced vital capacity (FVC): WMD 210 ml 95%CI 100 to 320. Two studies reported an improvement in maximum oxygen consumption (VO2 max); WMD 195 ml/min, 95%CI 113 to 278. At rest, arterial oxygen tension at rest (PaO2) and arterial carbon dioxide tension at rest (PaCO2) both improved with treatment (WMD 3.2 mm Hg; 95%CI 1.2 to 5.1, and WMD -2.4 mm Hg; 95%CI -3.5 to -1.2, respectively). Walking distance tests did not improve (four studies, Standardised Mean Difference 0.30, 95%CI -0.01 to 0.62), neither did Visual Analogue Score for breathlessness in two small studies (WMD 3.6, 95%CI -4.6 to 11.8). The Relative Risk (RR) of nausea was greater with theophylline (RR 7.7; 95%CI 1.5 to 39.9). However, patients' preference for theophylline was greater than that for placebo (RR 2.27; 95%CI 1.26 to 4.11). Very few participants withdrew from these studies for any reason. Theophylline has a modest effect on FEV1 and FVC and slightly improves arterial blood gas tensions in moderate to severe COPD. These benefits were seen in participants receiving a variety of different concomitant therapies. Improvement in exercise performance depended on the method of testing. There was a very low dropout rate in the studies that could be included in this review, which suggests that recruited participants may have been known by the investigators to be theophylline tolerant . This may limit the generalisability of these studies.",
        "gold": "This systematic review shows that orally administered theophylline improves lung function and levels of oxygen and carbon dioxide in the blood. However, there is limited data on its effect on symptoms, exercise capacity or quality of life. Despite being associated with increased side effects, particularly nausea, participants preferred theophylline over placebo."
    },
    {
        "index": "cochrane-simplification-test-337",
        "sentence": "We included 10 RCTs that met our inclusion criteria, that involved a total of 439 children (oral immunotherapy 249; control intervention 190), aged 1 year to 18 years. Each study used a different oral immunotherapy protocol; none used sublingual immunotherapy. Three studies used placebo and seven used an egg avoidance diet as the control. Primary outcomes were: an increased amount of egg that can be ingested and tolerated without adverse events while receiving allergen-specific oral immunotherapy or sublingual immunotherapy, compared to control; and a complete recovery from egg allergy after completion of oral immunotherapy or sublingual immunotherapy, compared to control. Most children (82%) in the oral immunotherapy group could ingest a partial serving of egg (1 g to 7.5 g) compared to 10% of control group children (RR 7.48, 95% CI 4.91 to 11.38; RD 0.73, 95% CI 0.67 to 0.80). Fewer than half (45%) of children receiving oral immunotherapy were able to tolerate a full serving of egg compared to 10% of the control group (RR 4.25, 95% CI 2.77 to 6.53; RD 0.35, 95% CI 0.28 to 0.43). All 10 trials reported numbers of children with serious adverse events (SAEs) and numbers of children with mild-to-severe adverse events. SAEs requiring epinephrine/adrenaline presented in 21/249 (8.4%) of children in the oral immunotherapy group, and none in the control group. Mild-to-severe adverse events were frequent; 75% of children presented mild-to-severe adverse events during oral immunotherapy treatment versus 6.8% of the control group (RR 8.35, 95% CI 5.31 to 13.12). Of note, seven studies used an egg avoidance diet as the control. Adverse events occurred in 4.2% of children, which may relate to accidental ingestion of egg-containing food. Three studies used a placebo control with adverse events present in 2.6% of children. Overall, there was inconsistent methodological rigour in the trials. All studies enrolled small numbers of children and used different methods to provide oral immunotherapy. Eight included studies were judged to be at high risk of bias in at least one domain. Furthermore, the quality of evidence was judged to be low due to small numbers of participants and events, and possible biases. Frequent and increasing exposure to egg over one to two years in people who are allergic to egg builds tolerance, with almost everyone becoming more tolerant compared with a minority in the control group and almost half of people being totally tolerant of egg by the end of treatment compared with 1 in 10 people who avoid egg. However, nearly all who received treatment experienced adverse events, mainly allergy-related. We found that 1 in 12 children had serious allergic reactions requiring adrenaline, and some people gave up oral immunotherapy. It appears that oral immunotherapy for egg allergy is effective, but confidence in the trade-off between benefits and harms is low; because there was a small number of trials with few participants, and methodological problems with some trials.",
        "gold": "We included 10 randomized controlled trials (studies that allocate people randomly by chance to receive treatment) that compared oral immunotherapy to placebo (a fake treatment not containing egg) or an egg-avoidance diet for people with egg allergy. The 10 studies included a total of 439 children (249 in the oral immunotherapy group (treatment containing egg) and 190 in the control group (no egg)) who were aged from 1 year to 18 years. The evidence showed that treating egg allergy by giving a small, increasing amount of egg may help most children with egg allergy to tolerate a partial serving of egg, so long as they continued to consume a daily amount of egg protein. Side effects were frequent during oral immunotherapy treatment, but were usually mild-to-moderate. Nevertheless, 21 of 249 children treated with oral immunotherapy for egg allergy required medicine because of a serious reaction. The studies did not report information about quality of life of children and their families during oral immunotherapy treatment. The trials involved small numbers and there were problems with the way they were done, therefore further research is needed."
    },
    {
        "index": "cochrane-simplification-test-338",
        "sentence": "We included four trials involving a total of 579 participants. With the limitation that only two studies reported data on mortality and none of them had considered death as a primary endpoint, the meta-analysis showed no evidence of a difference in the risk of long-term mortality between participants who received ILR and those who were managed conventionally at follow-up (RR 0.97, 95% CI 0.41 to 2.30; participants = 255; studies = 2; very low quality evidence) with no evidence of heterogeneity. No data on short term mortality were available. Two studies reported data on adverse events after ILR implant. Due to the lack of data on adverse events in one of the studies' arms, a formal meta-analysis was not performed for this outcome. Data from two trials seemed to show no difference in quality of life, although this finding was not supported by a formal analysis due to the differences in both the scores used and the way the data were reported. Data from two studies seemed to show a trend towards a reduction in syncope relapses after diagnosis in participants implanted with ILR. Cost analyses from two studies showed higher overall mean costs in the ILR group, if the costs incurred by the ILR implant were counted. The mean cost per diagnosis and the mean cost per arrhythmic diagnosis were lower for participants randomised to ILR implant. Participants who underwent ILR implantation experienced higher rates of diagnosis (RR (in favour of ILR) 0.61, 95% CI 0.54 to 0.68; participants = 579; studies = 4; moderate quality evidence), as compared to participants in the standard assessment group, with no evidence of heterogeneity. Our systematic review shows that there is no evidence that an ILR-based diagnostic strategy reduces long-term mortality as compared to a standard diagnostic assessment (very low quality evidence). No data were available for short-term all-cause mortality. Moderate quality evidence shows that an ILR-based diagnostic strategy increases the rate of aetiologic diagnosis as compared to a standard diagnostic pathway. No conclusive data were available on the other end-points analysed. Further trials evaluating the effect of ILRs in the diagnostic strategy of people with recurrent unexplained syncope are warranted. Future research should focus on the assessment of the ability of ILRs to change clinically relevant outcomes, such as quality of life, syncope relapse and costs.",
        "gold": "We searched scientific databases and found four randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) including 579 adults, which met our inclusion criteria. This review includes evidence identified up to April 2015. All-cause mortality (death from any cause) was no different in people who received the ILR. Loop recorders do not seem to change quality of life, although people with ILR had a significantly higher rate of diagnosis compared to participants in the standard assessment group. Moreover, data seem to show a trend towards a reduction in syncope recurrences after diagnosis in people implanted with ILR. Finally, costs were higher in the group of participants in which the ILR was implanted but the cost per diagnosis and the cost to diagnose an arrhythmia were much lower for participants randomised to ILR implant. There was low quality evidence that ILR does not change mortality if compared to a standard diagnostic assessment of people with syncope. There was moderate quality evidence that ILR increases the rate of diagnosis if compared to a standard diagnostic assessment. Future research is needed in order to clarify if ILRs can improve quality of life and reduce syncope recurrences and costs. All the included studies were funded: two of them by scientific societies, the remaining were partially supported by the ILR's manufacturers."
    },
    {
        "index": "cochrane-simplification-test-339",
        "sentence": "We found four small studies that met the inclusion criteria. These studies enrolled 275 patients with 282 hydroceles. Participants were randomised to aspiration and sclerotherapy (155 patients with 159 hydroceles) and surgery (120 patients with 123 hydroceles). All studies were assessed as having low or unclear risk of bias for selection bias, detection bias, attrition bias and selective reporting bias. Blinding was not possible for participants and investigators based on the type of interventions. Blinding for statisticians was not reported in any of included studies. There were no significant difference in clinical cure between the two groups (3 studies, 215 participants: RR 0.45, 95% CI 0.18 to 1.10), however there was significant heterogeneity (I\u00b2 = 95%). On further investigation one study contributed all of the heterogeneity. This could be due to the agent used or perhaps due to the fact that this is a much older study than the other two studies included in this analysis. When this study was removed from the analysis the heterogeneity was 0% and the result was significant (in favour of surgery) (2 studies, 136 participants: RR 0.74; 95% CI 0.64 to 0.85).There was a significant increase in recurrence in those who received sclerotherapy compared with surgery (3 studies, 196 participants: RR 9.37, 95% CI 1.83 to 48.4). One study reported a non-significant decrease in fever in the sclerotherapy group (60 participants: RR 0.25, 95% CI 0.06 to 1.08). There was an increased number of infections in the surgery group however this increase was not statistically significant (4 studies, 275 participants): RR 0.31, 95% CI 0.09 to 1.05; I\u00b2 = 0%). Three studies reported the frequency of pain in the surgery group was higher than aspiration and sclerotherapy group but because of different measurement tools applied in these studies, we could not pool the results. Radiological cure was not reported in any of the included studies. There was no significant difference in haematoma formation between the two groups (3 studies, 189 participants: RR 0.57, 95% CI 0.17 to 1.90; I\u00b2 = 0%). Only one study reported patient satisfaction at three and six months; there was no significant difference between the two groups. Postoperative complications as well as cost and time to work resumption were less in the aspiration and sclerotherapy group; however the recurrence rate was higher. The cure rate in short-term follow-up was similar between the groups, however there is significant uncertainty in this result due to the high heterogeneity. There is a great need for further methodologically rigorous RCTs that assess the effectiveness of different type of sclerosant agents, sclerosing solution concentration and injection volume for the treatment of hydrocoeles. It is important that the RCTs have sufficiently large sample size and long follow-up period. Studies should evaluate clinical outcomes such as pain, recurrence, satisfaction, complications and cure using validated instruments. The protocols for all studies should be registered in clinical trial registries and the reports of these studies should conform with international guidelines of trial reporting such as CONSORT. Cost-effectiveness studies should also be undertaken.",
        "gold": "The aim of this review is to compare these two types of treatment. We found four small studies were identified after an extensive literature search. Due to limited information about the design of the studies, and the small number of patients enrolled, the results should be interpreted with caution. Meta-analysis showed lower rates of recurrence in the surgery group, however there was insufficient evidence to draw a strong conclusion. Postoperative complications such as infection and fever, as well as cost and time to work resumption were less in the aspiration and sclerotherapy group; however the recurrence rate was higher. Cure at short-term follow-up was similar between the groups, however there is significant uncertainty in this result which may be as a result of the age of one of the studies and the different agent used compared to the other studies."
    },
    {
        "index": "cochrane-simplification-test-340",
        "sentence": "We included one RCT that compared nebulised recombinant human deoxyribonuclease (rhDNase) with placebo in 40 children with airway malacia and a respiratory tract infection. We assessed it to be a RCT with overall low risk of bias. Data analysed in this review showed that there was no significant difference between groups for the primary outcome of proportion cough-free at two weeks (odds ratio (OR) 1.38; 95% confidence interval (CI) 0.37 to 5.14). However, the mean change in night time cough diary scores significantly favoured the placebo group (mean difference (MD) 1.00; 95% CI 0.17 to 1.83, P = 0.02). The mean change in daytime cough diary scores from baseline was also better in the placebo group compared to those on nebulised rhDNase, but the difference between groups was not statistically significant (MD 0.70; 95% CI -0.19 to 1.59). Other outcomes (dyspnoea, and difficulty in expectorating sputum scores, and lung function tests at two weeks also favoured placebo over nebulised rhDNase but did not reach levels of significance. There is currently an absence of evidence to support any of the therapies currently utilised for management of intrinsic tracheomalacia. It remains inconclusive whether the use of nebulised rhDNase in children with airway malacia and a respiratory tract infection worsens recovery. It is unlikely that any RCT on surgically based management will ever be available for children with severe life-threatening illness associated with tracheomalacia. For those with less severe disease, RCTs on interventions such as antibiotics and chest physiotherapy are clearly needed. Outcomes of these RCTs should include measurements of the trachea and physiological outcomes in addition to clinical outcomes.",
        "gold": "We wanted to find out which out of these possible treatments was most effective. We found only one randomised controlled trial (RCT) that assessed nebulised recombinant human deoxyribonuclease (rhDNase) which helps in breaking down the mucous and has been shown to be useful in aiding airway clearance in cystic fibrosis compared to placebo (no active treatment) in children with both tracheomalacia and a concurrent respiratory infection. This trial showed no evidence of benefit in terms of the number of children who were cough-free two weeks after treatment. Also, there was less coughing reported, both during the day and at night, in the group who did not receive the intervention - however these differences were not statistically significant. With the lack of evidence, the routine use of any therapies for intrinsic tracheomalacia cannot be recommended given the cost of nebulised rhDNase and the likely harmful effect. The decision to subject a child to any surgical or medical based therapies will have to be made on an individual basis, with careful consideration of the risk-benefit ratio for each individual situation. It is unlikely that any RCT on surgically based management will ever be available for children with severe life-threatening illness associated with tracheomalacia. For those with less severe disease, RCTs on interventions such as antibiotics and chest physiotherapy are needed."
    },
    {
        "index": "cochrane-simplification-test-341",
        "sentence": "We included 21 studies with 2658 randomised participants. All studies assessed the effectiveness of some form of psychological therapy. We found no studies that included physical therapy. Fourteen studies evaluated forms of cognitive behavioural therapy (CBT); the remainder evaluated behaviour therapies, third-wave CBT (mindfulness), psychodynamic therapies, and integrative therapy. Fifteen included studies compared the studied psychological therapy with usual care or a waiting list. Five studies compared the intervention to enhanced or structured care. Only one study compared cognitive behavioural therapy with behaviour therapy. Across the 21 studies, the mean number of sessions ranged from one to 13, over a period of one day to nine months. Duration of follow-up varied between two weeks and 24 months. Participants were recruited from various healthcare settings and the open population. Duration of symptoms, reported by nine studies, was at least several years, suggesting most participants had chronic symptoms at baseline. Due to the nature of the intervention, lack of blinding of participants, therapists, and outcome assessors resulted in a high risk of bias on these items for most studies. Eleven studies (52% of studies) reported a loss to follow-up of more than 20%. For other items, most studies were at low risk of bias. Adverse events were seldom reported. For all studies comparing some form of psychological therapy with usual care or a waiting list that could be included in the meta-analysis, the psychological therapy resulted in less severe symptoms at end of treatment (SMD -0.34; 95% confidence interval (CI) -0.53 to -0.16; 10 studies, 1081 analysed participants). This effect was considered small to medium; heterogeneity was moderate and overall quality of the evidence was low. Compared with usual care, psychological therapies resulted in a 7% higher proportion of drop-outs during treatment (RR acceptability 0.93; 95% CI 0.88 to 0.99; 14 studies, 1644 participants; moderate-quality evidence). Removing one outlier study reduced the difference to 5%. Results for the subgroup of studies comparing CBT with usual care were similar to those in the whole group. Five studies (624 analysed participants) assessed symptom severity comparing some psychological therapy with enhanced care, and found no clear evidence of a difference at end of treatment (pooled SMD -0.19; 95% CI -0.43 to 0.04; considerable heterogeneity; low-quality evidence). Five studies (679 participants) showed that psychological therapies were somewhat less acceptable in terms of drop-outs than enhanced care (RR 0.93; 95% CI 0.87 to 1.00; moderate-quality evidence). When all psychological therapies included this review were combined they were superior to usual care or waiting list in terms of reduction of symptom severity, but effect sizes were small. As a single treatment, only CBT has been adequately studied to allow tentative conclusions for practice to be drawn. Compared with usual care or waiting list conditions, CBT reduced somatic symptoms, with a small effect and substantial differences in effects between CBT studies. The effects were durable within and after one year of follow-up. Compared with enhanced or structured care, psychological therapies generally were not more effective for most of the outcomes. Compared with enhanced care, CBT was not more effective. The overall quality of evidence contributing to this review was rated low to moderate. The intervention groups reported no major harms. However, as most studies did not describe adverse events as an explicit outcome measure, this result has to be interpreted with caution. An important issue was that all studies in this review included participants who were willing to receive psychological treatment. In daily practice, there is also a substantial proportion of participants not willing to accept psychological treatments for somatoform disorders or MUPS. It is unclear how large this group is and how this influences the relevance of CBT in clinical practice. The number of studies investigating various treatment modalities (other than CBT) needs to be increased; this is especially relevant for studies concerning physical therapies. Future studies should include participants from a variety of age groups; they should also make efforts to blind outcome assessors and to conduct follow-up assessments until at least one year after the end of treatment.",
        "gold": "We rated the quality of current research as low to moderate. Fourteen out of the 21 studies focused on cognitive behavioural therapy, which is a specific form of talking therapy based on the idea that thoughts and thinking can influence emotions and behaviours. Cognitive behavioural therapy was more effective than usual care in reducing the severity of MUPS. For other types of therapy, we found only one or two studies giving insufficient evidence for conclusions. Cognitive behavioural therapy was no more effective than enhanced care provided by the person's doctor. No studies of physical therapy met the criteria to be included in the review. Talking therapies were acceptable to people and few people dropped out of the trials; however, this may not reflect real clinical practice as the study participants were people with somatoform disorders or MUPS who were willing to try talking therapies. In clinical practice, a high proportion of people may not be willing to accept these treatments. The review authors suggest that future high-quality trials should be carried out to find out more about which groups of people benefit most from cognitive behavioural therapy and how it can be most effectively delivered. They also suggest that more studies are needed of other talking therapies, and a particular focus should be on high-quality studies of physical therapies."
    },
    {
        "index": "cochrane-simplification-test-342",
        "sentence": "In this updated review, we identified 40 new RCTs and seven ongoing studies. In total, we included 63 RCTs in the review, but we were only able to synthesize data on regional anaesthesia for the prevention of PPP beyond three months after surgery from 39 studies, enrolling a total of 3027 participants in our inclusive analysis. Evidence synthesis of seven RCTs favoured epidural anaesthesia for thoracotomy, suggesting the odds of having PPP three to 18 months following an epidural for thoracotomy were 0.52 compared to not having an epidural (OR 0.52 (95% CI 0.32 to 0.84, 499 participants, moderate-quality evidence). Simlarly, evidence synthesis of 18 RCTs favoured regional anaesthesia for the prevention of persistent pain three to 12 months after breast cancer surgery with an OR of 0.43 (95% CI 0.28 to 0.68, 1297 participants, low-quality evidence). Pooling data at three to 8 months after surgery from four RCTs favoured regional anaesthesia after caesarean section with an OR of 0.46, (95% CI 0.28 to 0.78; 551 participants, moderate-quality evidence). Evidence synthesis of three RCTs investigating continuous infusion with local anaesthetic for the prevention of PPP three to 55 months after iliac crest bone graft harvesting (ICBG) was inconclusive (OR 0.20, 95% CI 0.04 to 1.09; 123 participants, low-quality evidence). However, evidence synthesis of two RCTs also favoured the infusion of intravenous local anaesthetics for the prevention of PPP three to six months after breast cancer surgery with an OR of 0.24 (95% CI 0.08 to 0.69, 97 participants, moderate-quality evidence). We did not synthesize evidence for the surgical subgroups of limb amputation, hernia repair, cardiac surgery and laparotomy. We could not pool evidence for adverse effects because the included studies did not examine them systematically, and reported them sparsely. Clinical heterogeneity, attrition and sparse outcome data hampered evidence synthesis. High risk of bias from missing data and lack of blinding across a number of included studies reduced our confidence in the findings. Thus results must be interpreted with caution. We conclude that there is moderate-quality evidence that regional anaesthesia may reduce the risk of developing PPP after three to 18 months after thoracotomy and three to 12 months after caesarean section. There is low-quality evidence that regional anaesthesia may reduce the risk of developing PPP three to 12 months after breast cancer surgery. There is moderate evidence that intravenous infusion of local anaesthetics may reduce the risk of developing PPP three to six months after breast cancer surgery. Our conclusions are considerably weakened by the small size and number of studies, by performance bias, null bias, attrition and missing data. Larger, high-quality studies, including children, are needed. We caution that except for breast surgery, our evidence synthesis is based on only a few small studies. On a cautionary note, we cannot extend our conclusions to other surgical interventions or regional anaesthesia techniques, for example we cannot conclude that paravertebral block reduces the risk of PPP after thoracotomy. There are seven ongoing studies and 12 studies awaiting classification that may change the conclusions of the current review once they are published and incorporated.",
        "gold": "The evidence is current to December 2016. We found 63 randomized controlled trials (RCTs) with participants undergoing open chest, heart, breast, abdominal, vascular, gynaecological and other surgery, but not orthopaedic surgery. RCTs are studies where people are allocated by chance to one or the other of different treatments being studied. The studies included only adults, and were mostly conducted in Europe and North America, with some from China, Egypt and Brazil. The types of surgery included surgery with a high event rate of persistent pain after surgery, such as breast surgery, limb amputation and opening the chest, and surgery with a lower risk but high numbers of procedures, such as caesarean section. We were able to pool results from 39 RCTs enrolling a total of 3027 participants for our inclusive analysis. Follow-up was for 1293 participants at three months, 1365 participants at six months, 326 participants at 12 months, and 43 participants at 20 or more months after surgery. The RCTs did not report surgical and anaesthetic complications consistently and little information was available on these. The studies were mostly funded by the institutions conducting the studies. Regional anaesthesia reduced the number of people who experienced persistent pain after undergoing non-orthopaedic surgery. For open chest surgery, giving an epidural halved the odds of a person having persistent postoperative pain at three to 18 months after surgery (7 RCTs, 499 participants, moderate-quality evidence). Seven people needed to be treated in this way for one to benefit. For the prevention of persistent pain three to 12 months after breast cancer surgery, seven people needed regional anaesthesia for one to benefit (18 RCTs, 1297 participants, low-quality evidence). Infusion of local anaesthetic into a vein was shown to reduce the risk of persistent pain three to six months after breast surgery (2 RCTs, 97 participants, moderate-quality evidence), with three people needing to be treated for one to benefit. Regional anaesthesia reduced the odds by more than half of a woman experiencing persistent pain after caesarean section (4 RCTs, 551 participants, moderate-quality evidence). The number of women treated for one to benefit was 19. Continuous local anaesthetic infusion of the site where bone tissue was obtained from the hip bone did not clearly reduce the number of people with persistent pain at three to 55 months (3 RCTs, 123 participants, low-quality evidence). We could not synthesize evidence for limb amputation, hernia repair, cardiac or abdominal surgery because of differences in how treatment was given or how results were reported. We found consistent evidence supporting the use of regional anaesthesia in adults to prevent persistent pain after a number of types of surgery. However, we observed variations in the effect sizes, and at different times after surgery. Some studies could not be blinded to the treatment received and our results are affected by the small number of studies and participants, and the loss to follow-up of participants over time. The evidence was therefore of low or moderate quality."
    },
    {
        "index": "cochrane-simplification-test-343",
        "sentence": "Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants. The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed. Adverse event data were scarce, except for olanzapine. There was a possible increase in self-harming behaviour, significant weight gain, sedation and changes in haemogram parameters with olanzapine. A significant decrease in body weight was observed with topiramate treatment. All drugs were well tolerated in terms of attrition. Direct drug comparisons comprised two first-generation antipsychotics (loxapine versus chlorpromazine), first-generation antipsychotic against antidepressant (haloperidol versus amitriptyline; haloperidol versus phenelzine sulfate), and second-generation antipsychotic against antidepressant (olanzapine versus fluoxetine). Data indicated better outcomes for phenelzine sulfate but no significant differences in the other comparisons, except olanzapine which showed more weight gain and sedation than fluoxetine. The only trial testing single versus combined drug treatment (olanzapine versus olanzapine plus fluoxetine; fluoxetine versus fluoxetine plus olanzapine) yielded no significant differences in outcomes. The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).",
        "gold": "Available studies tested the effects of antipsychotic, antidepressant and mood stabiliser treatment in BPD. In addition, the dietary supplement omega-3 fatty acid (commonly derived from fish) which is supposed to have mood stabilising effects was tested. Twenty-eight studies covering 1742 study participants were included. The findings tended to suggest a benefit from using second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but most effect estimates were based on single study effects so repeat studies would be useful. Moreover, the long-term use of these drugs has not been assessed. The small amount of available information for individual comparisons indicated marginal effects for first-generation antipsychotics and antidepressants. The data also indicated that there may be an increase in self-harming behaviour in patients treated with olanzapine. In general, attention must be paid to adverse effects. Most trials did not provide detailed data of adverse effects and thus could not be considered within this review. We assumed their effects were similar to those experienced by patients with other conditions. Available data of the studies included here suggested adverse effects included weight gain, sedation and change of haemogram parameters with olanzapine treatment, and weight loss with topiramate. Very few beneficial effects were identified for first-generation antipsychotics and antidepressants. However, they may be helpful in the presence of comorbid problems that are not part of BPD core pathology, but can often be found in BPD patients. There are only few study results per drug comparison, with small numbers of included participants. Thus, current findings of trials and this review are not robust and can easily be changed by future research endeavours. In addition, the studies may not adequately reflect several characteristics of clinical settings (among others, patients' characteristics and duration of interventions and observation periods)."
    },
    {
        "index": "cochrane-simplification-test-344",
        "sentence": "We included seven trials involving a total of 349 participants, 217 of whom completed the studies. Three were cross-over and four were parallel-group randomised controlled trials (RCTs). Of these, two trials were added for this update (one parallel-group RCT with 40 participants and one cross-over RCT with 67 participants). Analyses of three cross-over trials yielded suboptimal results because they were based on between-group differences rather than individual participants' differences for sequential interventions. Two parallel-group trials had limited clinical value: one combined results for suprapubic and urethral catheters and the other provided data for only four participants. Only one trial was free of significant methodological limitations, but there were difficulties with recruitment and maintaining participants in this study. The included studies reported data on six of the nine primary and secondary outcome measures. None of the trials addressed: number of catheters used, washout acceptability measures (including patient satisfaction, patient discomfort, pain and ease of use), or health status/measures of psychological health; very limited data were collected for health economic outcomes. Trials assessed only three of the eight intervention comparisons identified. Two trials reported in more than one comparison group. Four trials compared washout (either saline or acidic solution) with no washout. We are uncertain if washout solutions (saline or acidic), compared to no washout solutions, has an important effect on the rate of symptomatic urinary tract infection or length of time each catheter was in situ because the results are imprecise. Four trials compared different types of washout solution; saline versus acidic solutions (2 trials); saline versus acidic solution versus antibiotic solution (1 trial); saline versus antimicrobial solution (1 trial). We are uncertain if type of washout solution has an important effect on the rate of symptomatic urinary tract infection or length of time each catheter was in situ because the results are imprecise. One trial compared different compositions of acidic solution (stronger versus weaker solution). We are uncertain if different compositions of acidic solutions has an important effect on the rate of symptomatic urinary tract infection or length of time each catheter was in situ because only 14 participants (of 25 who were recruited) completed this 12 week, three arm trial. Four studies reported on possible harmful effects of washout use, such as blood in the washout solution, changes in blood pressure and bladder spasms. There were very few small trials that met the review inclusion criteria. The high risk of bias of the included studies resulted in the evidence being graded as low or very low quality. Data from seven trials that compared different washout policies were limited, and generally, of poor methodological quality or were poorly reported. The evidence was not adequate to conclude if washouts were beneficial or harmful. Further rigorous, high quality trials that are adequately powered to detect benefits from washout being performed as opposed to no washout are needed. Trials comparing different washout solutions, washout volumes, and frequencies or timings are also needed.",
        "gold": "We included seven studies that presented information on 217 people who completed the studies of 349 who started in the trials. Two studies were new for this update. The studies, published between 1979 and 2014, were conducted in the USA (3 studies), the UK (2 studies), and one each in Canada and Finland. The studies included people with long-term catheters. People were allocated randomly to have catheter washouts or not, and the effects compared. We also included studies that compared different types of washout solutions. Four studies reported on possible harmful effects of washout use, such as blood in the washout solution, changes in blood pressure and bladder spasms. The included studies were funded by Novobay Pharmaceuticals Inc (Linsenmeyer 2014); Alberta Heritage Foundation for Medical Research and the Canadian Nurses Foundation (Moore 2009); National institute of Aging, National Institutes of Health (Muncie 1989); Paralyzed Veterans of America Spinal Cord Research Foundation (Waites 2006). Three studies did not report funding sources. There was not enough good research evidence to determine if catheter washouts were useful. The included trials were generally small with methodological flaws. This included limited details on how participants were randomly allocated into groups and how both participants and researchers were blinded to these groups. Evidence quality was low to very low. New trials are needed to definitively answer this research question."
    },
    {
        "index": "cochrane-simplification-test-345",
        "sentence": "We included 30 studies (18,682 participants in total). Eighteen studies contributed to the main objective and 22 studies contributed to the secondary objectives. We found substantial differences between studies in cancer diagnosis, cancer treatment, age of participants, questionnaires used to assess fatigue, and sample size. All included studies scored at least one 'Risk of bias' item as unclear or high risk. We identified both clinical and statistical heterogeneity and therefore could not pool results, so we present them descriptively. Eighteen studies (describing 14,573 survivors) reported the prevalence of severe fatigue, which ranged from 0% to 61.7%. In a subgroup of three studies including children aged up to 18 years at fatigue assessment (268 survivors), prevalence rates ranged from 6.7% to 12.5%. In comparison, in a subgroup of 12 studies including participants aged 16 and over (13,952 survivors), prevalence rates ranged from 4.4% to 61.7%. The prevalence of severe fatigue in a subgroup of survivors of haematological cancer was presented in seven studies and ranged from 1.8% to 35.9% (1907 survivors). Prevalence of severe fatigue in brain cancer survivors was presented in two studies (252 survivors) and was 14.6% and 21.1% respectively. One study presented a prevalence for bone cancer survivors of 0.0% (17 survivors). Four studies provided prevalence rates of severe fatigue in control groups of siblings or population-based controls, which ranged from 3.1% to 10.3%. In these four studies, survivors were more often fatigued than controls, but this difference was statistically significant in only two studies. Studies assessing risk and associated factors for fatigue were heterogeneous, and definitions of the factors under study were often inconsistent, with results therefore presented descriptively. They found that depression might be associated with fatigue. In contrast, age at diagnosis and education level did not seem to be associated with fatigue. We were unable to calculate any overall risk estimate for any of the reported risks and associated factors, because we could not conduct meta-analysis. One study provided information about the course of fatigue over time, and found that over the course of 2.7 years, 32 of the 102 participants (31.4%) reported persistent severe fatigue. It is unclear how many childhood cancer survivors suffer from severe fatigue. This review encountered several difficulties. We found statistical and clinical heterogeneity and great variation in the reporting of possible risk and associated factors. The evidence in this review is therefore weak, and the exact prevalence of severe fatigue after treatment for childhood cancer remains to be determined. This is also the case for the course of severe fatigue following treatment and the strength of the relationship between fatigue and associated and risk factors. Despite these limitations, our review does provide a comprehensive overview of the existing literature about severe fatigue after treatment for childhood cancer.",
        "gold": "The evidence is up to date to March 2019. We include 30 studies, describing 18,682 participants after treatment for childhood cancer. We found a lot of variation between studies in cancer diagnosis, cancer treatment, age of participants, the questionnaires used to assess fatigue, and the size of the study. Eighteen studies reported a prevalence of severe fatigue, which ranged from 0% to 61.7%. Four studies reported a prevalence of severe fatigue in the patient's brothers and sisters or in population-based controls. Prevalence rates in these control groups ranged from 3.1% to 10.3%. In these four studies, survivors were more often fatigued than controls. This difference was only significant in two studies. When we looked at the prevalence of severe fatigue in survivors of lymphoma and leukaemia (types of blood cancers), we found that they ranged from 1.8% to 35.9%. Two studies reported on severe fatigue in brain cancer survivors, with rates of 21.13% and 14.6%. One study in bone cancer survivors reported no cases of severe fatigue. For survivors aged 18 and younger, prevalence rates ranged from 6.7% to 12.5%. By contrast, in studies including participants aged 16 years and over (but mostly over 18), prevalence rates ranged from 4.4% to 61.7%. Twenty-two studies assessed one or more possible risk factors for fatigue. Our review shows that depression might increase fatigue. The age at cancer diagnosis and the education level of the survivor did not seem to influence fatigue. Only one study provided information about the course of fatigue over time, and found that over the course of 2.7 years 32 of the 102 participants (31.4%) reported persistent severe fatigue. All included studies had problems with the quality of the evidence, and we found many differences between studies for several characteristics. The evidence to address our review question is therefore weak. The occurrence of severe fatigue after treatment for childhood cancer remains uncertain. This is also the case for the course of severe fatigue after completion of cancer treatment and the risk factors that might be responsible for developing fatigue."
    },
    {
        "index": "cochrane-simplification-test-346",
        "sentence": "We included 36 trials involving 6914 people. There was variation in the antibiotics used, patient characteristics and risk of RTIs and mortality in the control groups. In trials comparing a combination of topical and systemic antibiotics, there was a significant reduction in both RTIs (number of studies = 16, odds ratio (OR) 0.28, 95% confidence interval (CI) 0.20 to 0.38) and total mortality (number of studies = 17, OR 0.75, 95% CI 0.65 to 0.87) in the treated group. In trials comparing topical antimicrobials alone (or comparing topical plus systemic versus systemic alone) there was a significant reduction in RTIs (number of studies = 17, OR 0.44, 95% CI 0.31 to 0.63) but not in total mortality (number of studies = 19, OR 0.97, 95% CI 0.82 to 1.16) in the treated group. A combination of topical and systemic prophylactic antibiotics reduces RTIs and overall mortality in adult patients receiving intensive care. Treatment based on the use of topical prophylaxis alone reduces respiratory infections but not mortality. The risk of resistance occurring as a negative consequence of antibiotic use was appropriately explored only in one trial which did not show any such effect.",
        "gold": "This review includes 36 studies involving 6914 patients treated in ICUs to investigate whether the administration of antibiotics prevents the development of infections. Antibiotics were administered in two different ways. In some studies antibiotics were applied both directly to the oropharynx via a nasogastric tube (topical) and intravenously (systemic). In other studies they were applied only topically. Our results show that when patients received the combination of topical plus systemic antibiotics there were less infections and deaths. When patients received only topical treatment there were less infections but the number of deaths was not changed. Although this treatment seems to work it is not widely used in clinical practice because there is concern about the possible development of antibiotic resistance (that is, bacteria become unresponsive to drugs)."
    },
    {
        "index": "cochrane-simplification-test-347",
        "sentence": "Five cluster-randomised controlled studies met the inclusion criteria. All of them investigated educational approaches. Two studies offered consultation in addition and two other studies offered guidance for nursing staff in addition. Four studies examined nursing home residents and one study residents in group dwelling units. No studies in community settings were included. Three studies included only one or two nursing homes per study condition. Overall, methodological quality of studies was low. The studies revealed inconsistent results. One study in the nursing home setting documented an increase of PR use in both groups after eight months, while the other three studies found reduced use of PR in the intervention groups after seven and 12 months of follow up respectively. The single study examining residents in group dwelling units found no change in PR use in the intervention group after six months whereas PR use increased significantly in the control group. There is insufficient evidence supporting the effectiveness of educational interventions targeting nursing staff for preventing or reducing the use of physical restraints in geriatric long-term care.",
        "gold": "We reviewed whether interventions aimed at preventing and reducing the use of PR in geriatric long-term care settings are effective. We identified five small-sized randomised controlled studies suitable for inclusion. All studies examined educational interventions targeted at nursing staff. Four studies investigated residents in nursing homes and one in group dwelling units. The methodological quality of all studies was limited. Results of the studies were inconsistent. One study with higher methodological quality showed no reduction in PR use. Three other studies with lower methodological quality found their intervention to be effective. Thus, current evidence on interventions for the reduction or prevention of PR use in long-term geriatric care does not support a clear conclusion. Ongoing and unpublished research might alter the results of the review."
    },
    {
        "index": "cochrane-simplification-test-348",
        "sentence": "Four RCTs were included in the review (416 women). The trials compared glucocorticoid supplementation during IVF stimulation versus placebo. Two of the studies had data in a form that we could not enter into analysis, so results include data from only two trials (310) women. For the outcome of live birth, data were available for only 212 women, as the larger study had data available from only one study centre. One of the studies gave inadequate description of randomisation methods, but the other was at low risk of bias in all domains. The evidence was rated as low or very low quality for all outcomes, mainly due to imprecision, with low sample sizes and few events. There was insufficient evidence to determine whether there was any difference between the groups in live birth rate (OR 1.08, 95% CI 0.45 to 2.58; 2 RCTs, n = 212, I2 = 0%, low-quality evidence). Our findings suggest that if the chance of live birth with placebo is assumed to be 15%, the chance following supplementation would be between 7% and 31%. There was no conclusive evidence of a difference in the clinical pregnancy rate (OR 1.69, 95% CI 0.98 to 2.90; 2 RCTs, n = 310, I2 = 0%, low-quality evidence).The evidence suggests that if the chance of clinical pregnancy with placebo is assumed to be 24%, the chance following treatment with glucocorticoid supplementation would be between 23% and 47%. There was also insufficient evidence to determine whether there was any difference between the groups in multiple-pregnancy rate (OR 3.32 , 95% CI 0.12 to 91.60; 1 RCT , n = 20, very low-quality evidence) or miscarriage rate (OR 1.00, 95% CI 0.05 to 18.57; 1 RCT, n = 20, very low-quality evidence). Neither of the studies reported OHSS or side-effects. The safety and effectiveness of glucocorticoid administration in women undergoing controlled ovarian hyperstimulation for IVF/ICSI cycles (until the day of oocyte retrieval) is unclear due to the small number of studies and low event rates. Whilst glucocorticoids possibly\u00a0increase the clinical pregnancy rate, there may be little or no impact on live birth rate. More research is needed.",
        "gold": "We found four randomised controlled trials (RCTs), but useable data were available for only two of these. The trials compared adjuvant treatment with systemic glucocorticoids during ovarian stimulation for IVF cycles versus no placebo. The evidence is current to October 2016. Key results Two RCTs were included in our analyses (310 women). For the outcome of live birth, data were available for only 212 women, as the larger study had data available from only one study centre. There was no conclusive evidence of a difference in the primary outcome of live birth rate and the secondary outcome of clinical pregnancy rate. Our findings suggest that if the chance of live birth with placebo is assumed to be 15%, the chance following supplementation would be between 7% and 31%, and that if the chance of clinical pregnancy with placebo is assumed to be 24%, the chance following treatment with supplementation would be between 23% and 47%. There was also insufficient evidence to determine whether there was any difference between the groups in the multiple-pregnancy rate or miscarriage rate. Neither of the studies reported ovarian hyperstimulation syndrome (OHSS) or side-effects. Thus, the safety and effectiveness of glucocorticoid administration in women undergoing controlled ovarian hyperstimulation for IVF/ICSI cycles (until the day of oocyte retrieval) is unclear due to the small number of studies and low event rates. Whilst glucocorticoids possibly increase the clinical pregnancy rate, there may be little or no impact on the live birth rate. The evidence was rated as low or very low quality for all outcomes, mainly due to imprecision, with low sample sizes and few events."
    },
    {
        "index": "cochrane-simplification-test-349",
        "sentence": "We included eight trials (291 participants, aged between five and 23 years) in this revision of the review. Seven trials compared standard-dose rhGH (approximately 0.3 mg/kg/week) to no treatment and one three-arm trial (63 participants) compared placebo, standard-dose rhGH (0.3 mg/kg/week) and high-dose rhGH (0.5 mg/kg/week). Six trials lasted for one year and two trials for six months. We found that rhGH treatment may improve some of the pulmonary function outcomes but there was no difference between standard and high-dose levels (low-quality evidence, limited by inconsistency across the trials, small number of participants and short duration of therapy). The trials show evidence of improvement in the anthropometric parameters (height, weight and lean body mass) with rhGH therapy, again no differences between dose levels. We found improvement in height for all comparisons (very low- to low quality evidence), but improvements in weight and lean body mass were only reported for standard-dose rhGH versus no treatment (very low-quality evidence). There is some evidence indicating a change in the level of fasting blood glucose with rhGH therapy, however, it did not cross the clinical threshold for diagnosis of diabetes in the trials of short duration (low-quality evidence). There is low- to very low-quality evidence for improvement of pulmonary exacerbations with no further significant adverse effects, but this is limited by the short duration of trials and the small number of participants. One small trial provided inconsistent evidence on improvement in quality of life (very low-quality evidence). There is limited evidence from three trials in improvements in exercise capacity (low-quality evidence). None of the trials have systematically compared the expense of therapy on overall healthcare costs. When compared with no treatment, rhGH therapy is effective in improving the intermediate outcomes in height, weight and lean body mass. Some measures of pulmonary function showed moderate improvement, but no consistent benefit was seen across all trials. The significant change in blood glucose levels, although not causing diabetes, emphasizes the need for careful monitoring of this adverse effect with therapy in a population predisposed to CF-related diabetes. No significant changes in quality of life, clinical status or side-effects were observed in this review due to the small number of participants. Long-term, well-designed randomised controlled trials of rhGH in individuals with CF are required prior to routine clinical use of rhGH in CF.",
        "gold": "This review looked at using of rhGH to improve lung function, growth and quality of life for children and young adults with CF. It includes eight trials with 291 individuals with CF being selected for one treatment or the other randomly. The individuals in the trials were five to 23 years old, but most had not yet reached puberty. Six trials lasted for one year and two trials for six months. Treatment with rhGH was compared to no treatment in seven trials and to a placebo (a liquid that did not contain any growth hormone) in one trial. The trial that used a placebo compared it to two different doses of rhGH treatment. Results showed a modest improvement in height, weight and lean body mass between six and 12 months. However, there was no consistent evidence that rhGH treatment improves lung function, muscle strength, or quality of life. The trials were small and we did not find any evidence on changes in glucose metabolism or the long-term risk of diabetes due to the treatment. Given these results, we are not able to identify any clear benefit of therapy and believe that more research from well-designed, adequately powered clinical trials is needed. We did not have enough information to decide if overall the trials were biased in a way that might affect the results. All the measured outcomes were clearly reported in the trials, but the trials were small, and did not have enough participants to show a difference that may not have been due to chance. We also had concerns that outcomes which were based on personal judgement, such as quality of life scores, might be affected because those taking part in seven of the trials were able to tell which group they were in."
    },
    {
        "index": "cochrane-simplification-test-350",
        "sentence": "We included 26 non-randomized controlled before and after studies with 1,695 participants that reported on three comparisons: complete removal from exposure and reduced exposure compared to continued exposure, and complete removal from exposure compared to reduced exposure. Reduction of exposure was achieved by limiting use of the agent, improving ventilation, or using protective equipment in the same job; by changing to another job with intermittent exposure; or by implementing education programs. For continued exposure, 56 per 1000 workers reported absence of symptoms at follow-up, the decrease in forced expiratory volume in one second as a percentage of a reference value (FEV1 %) was 5.4% during follow-up, and the standardized change in non-specific bronchial hyperreactivity (NSBH) was -0.18. In 18 studies, authors compared removal from exposure to continued exposure. Removal may increase the likelihood of reporting absence of asthma symptoms, with risk ratio (RR) 4.80 (95% confidence interval (CI) 1.67 to 13.86), and it may improve asthma symptoms, with RR 2.47 (95% CI 1.26 to 4.84), compared to continued exposure. Change in FEV1 % may be better with removal from exposure, with a mean difference (MD) of 4.23 % (95% CI 1.14 to 7.31) compared to continued exposure. NSBH may improve with removal from exposure, with standardized mean difference (SMD) 0.43 (95% CI 0.03 to 0.82). In seven studies, authors compared reduction of exposure to continued exposure. Reduction of exposure may increase the likelihood of reporting absence of symptoms, with RR 2.65 (95% CI 1.24 to 5.68). There may be no considerable difference in FEV1 % between reduction and continued exposure, with MD 2.76 % (95% CI -1.53 to 7.04) . No studies reported or enabled calculation of change in NSBH. In ten studies, authors compared removal from exposure to reduction of exposure. Following removal from exposure there may be no increase in the likelihood of reporting absence of symptoms, with RR 6.05 (95% CI 0.86 to 42.34), and improvement in symptoms, with RR 1.11 (95% CI 0.84 to 1.47), as well as no considerable change in FEV1 %, with MD 2.58 % (95% CI \u22123.02 to 8.17). However, with all three outcomes, there may be improved results for removal from exposure in the subset of patients exposed to low molecular weight agents. No studies reported or enabled calculation of change in NSBH. In two studies, authors reported that the risk of unemployment after removal from exposure may increase compared with reduction of exposure, with RR 14.28 (95% CI 2.06 to 99.16). Four studies reported a decrease in income of 20% to 50% after removal from exposure. The quality of the evidence is very low for all outcomes. Both removal from exposure and reduction of exposure may improve asthma symptoms compared with continued exposure. Removal from exposure, but not reduction of exposure, may improve lung function compared to continued exposure. When we compared removal from exposure directly to reduction of exposure, the former may improve symptoms and lung function more among patients exposed to low molecular weight agents. Removal from exposure may also increase the risk of unemployment. Care providers should balance the potential clinical benefits of removal from exposure or reduction of exposure with potential detrimental effects of unemployment. Additional high-quality studies are needed to evaluate the effectiveness of workplace interventions for occupational asthma.",
        "gold": "The review is based on 26 studies that included 1,695 participants with occupational asthma. Sensitizers caused nearly all cases. We focused on the interventions of removal from exposure and reduction of exposure, which were compared with continued exposure. Outcomes were changes in asthma symptoms, lung function, and non-specific bronchial hyperreactivity between baseline and follow-up. What are the main results of the review? Both removal from exposure and reduction of exposure may improve asthma symptoms when compared to continued exposure. Removal from exposure, but not reduction of exposure, may improve lung function when compared to continued exposure. Removal from exposure may improve symptoms and lung function more than reduction of exposure among patients exposed to low molecular weight agents, but removal may also increase the risk of unemployment. Consequently, the benefit of a better improvement has to be weighed against the potential for a higher risk of job loss. Further research is needed to determine the effectiveness of interventions at reducing the impact of occupational asthma. How up-to-date is this review? We searched for studies that had been published through 31July 2019."
    },
    {
        "index": "cochrane-simplification-test-351",
        "sentence": "The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects. In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.",
        "gold": "We found six trials with 1758 participants. Of these, five studies looked at on-demand deprescribing and one trial looked at abruptly stopping PPIs. Participants were aged 48 to 57 years, except for one trial (average age of 73 years). The majority of participants had moderate heart burn and acid reflux with milder forms of esophagitis (inflammation of the food pipe that may lead to damage). We found that deprescribing methods led to worse symptoms control while considerably reducing pill use. Deprescribing PPIs may lead to side effects such as inflammation of the esophagus. Very few data were available to make a conclusion regarding long-term benefits and harms of PPI reduction or discontinuation. Overall, the quality of evidence for this review ranged from very low to moderate. Trials were inconsistent with how they reported symptom control. There were also limitations in how the studies were conducted (e.g. participants and investigators may have known which medicine they received), which lowered the quality of evidence. Other contributing factors included small sample sizes for most trials and inconsistent results between studies."
    },
    {
        "index": "cochrane-simplification-test-352",
        "sentence": "We included 13 randomised trials (975 participants). These evaluated social skills programmes versus standard care, or discussion group. We found evidence in favour of social skills programmes compared to standard care on all measures of social functioning. We also found that rates of relapse and rehospitalisation were lower for social skills compared to standard care (relapse: 2 RCTs, n = 263, RR 0.52 CI 0.34 to 0.79, very low quality evidence), (rehospitalisation: 1 RCT, n = 143, RR 0.53 CI 0.30 to 0.93, very low quality evidence) and participants\u2019 mental state results (1 RCT, n = 91, MD -4.01 CI -7.52 to -0.50, very low quality evidence) were better in the group receiving social skill programmes. Global state was measured in one trial by numbers not experiencing a clinical improvement, results favoured social skills (1 RCT, n = 67, RR 0.29 CI 0.12 to 0.68, very low quality evidence). Quality of life was also improved in the social skills programme compared to standard care (1 RCT, n = 112, MD -7.60 CI -12.18 to -3.02, very low quality evidence). However, when social skills programmes were compared to a discussion group control, we found no significant differences in the participants social functioning, relapse rates, mental state or quality of life, again the quality of evidence for these outcomes was very low. Compared to standard care, social skills training may improve the social skills of people with schizophrenia and reduce relapse rates, but at present, the evidence is very limited with data rated as very low quality. When social skills training was compared to discussion there was no difference on patients outcomes. Cultural differences might limit the applicability of the current results, as most reported studies were conducted in China. Whether social skills training can improve social functioning of people with schizophrenia in different settings remains unclear and should be investigated in a large multi-centre randomised controlled trial.",
        "gold": "The main objective of this review is to investigate the effectiveness of social skills programmes, compared to standard care or discussion groups, for people with schizophrenia. Based on searches carried out in 2006 and 2011, this review includes 13 trials with a total of 975 participants. Authors chose seven main outcomes of interest, all data for these outcomes were rated to be very low quality. The review found significant differences in favour of social skills programmes compared to standard care on all measures of social functioning. Rates of relapse were lower for social skills compared to standard care and there was a significant difference in favour of social skills on people\u2019s mental state. Quality of life was also improved in the social skills programme compared to standard care. However, when social skills programmes were compared to discussion groups, there were no significant differences in people\u2019s social functioning, relapse rates, mental state or quality of life. Compared to standard care, social skills programmes may improve the social skills of people with schizophrenia and reduce relapse rates. However, at the moment evidence is very limited with data only of very low quality available. Cultural differences might also limit the relevance of current results, as most reported studies were conducted in China. Whether social skills programmes or training can improve the social functioning of people with schizophrenia in different settings remains unclear and should be further investigated in a large multi-centre randomised controlled trial. Ben Gray, Senior Peer Researcher, McPin Foundation.http://mcpin.org/"
    },
    {
        "index": "cochrane-simplification-test-353",
        "sentence": "Only one study, at low risk of all biases, met the inclusion criteria. This was the pooled results from two RCTs (225 participants, 145 with tophi at baseline) randomised to one of three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Moderate-quality evidence from one study indicated that biweekly pegloticase 8 mg infusion reduced tophi in the subset of participants with tophi, but increased withdrawals due to adverse events in all participants, and monthly infusion appeared to result in less benefit. Biweekly pegloticase treatment resulted in resolution of tophi in 21/52 participants compared with 2/27 who received placebo (risk ratio (RR) 5.45, 95% confidence intervals (CI) 1.38 to 21.54; number needed to treat for an additional beneficial outcome (NNTB) 3 (95% CI 2 to 6). Eleven of 52 participants with monthly pegloticase treatment had complete resolution of one or more tophi compared with 2/27 who received placebo (RR 2.86, 95% CI 0.68 to 11.97). Participant-reported pain relief of 30% or greater, function, quality of life, serum urate normalisation, were reported for all participants but not separately for those with tophi; therefore, we did not include the results. Pegloticase administered biweekly resulted in more withdrawals due to adverse events compared with placebo (15/85 participants with pegloticase versus 1/43 participants with placebo; RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for an additional harmful outcome (NNTH) 7, 95% CI 4 to 17). Pegloticase administered monthly also resulted in more withdrawals due to adverse events than placebo (16/84 participants with pegloticase versus 1/43 participants with placebo; RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Most withdrawals were due to infusion reactions. Total adverse events were high in all treatment groups: 80/85 participants administered pegloticase biweekly reported an adverse event compared with 41/43 from the placebo group (RR 0.99, 95% CI 0.91 to 1.07); 84/84 participants administered pegloticase monthly reported an adverse event versus 41/43 in the placebo group (RR 1.05, 95% CI 0.98 to 1.14). As 80% of adverse events were due to flares of gout, probably unrelated to the drug treatment per se, this may explain the high rate of adverse events in the placebo group - who were essentially untreated. This study showed pegloticase is probably beneficial in the management of tophi in gout, in terms of resolution of tophi, but with a high risk of adverse infusion reactions. However, there is a need for more RCT data considering other interventions, including surgical removal of tophi.",
        "gold": "This is a summary of a Cochrane review that shows interventions for the management of tophi. After searching for all relevant studies in May 2013, we found only one study (pooled results from two randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups)) that randomised 225 people to pegloticase (every two weeks (biweekly) or monthly) or placebo, in the management of chronic gout; 145 participants had tophi and 131 contributed outcome data. Resolution of tophi - 33 more people out of 100 had resolution of one or more tophi after six months' treatment with pegloticase biweekly compared with placebo (33% absolute improvement). - 14 more people out of 100 had resolution of one or more tophi after six months' treatment with pegloticase monthly compared with placebo (14% absolute improvement). - 40 people out of 100 in the biweekly pegloticase group had resolution of one or more tophi. - 21 people out of 100 in the monthly pegloticase group had resolution of one or more tophi. - 7 people out of 100 in the placebo group had resolution of one or more tophi. Other outcomes were for all participants, and not separated out for those people with tophi. Therefore, we have not reported them in this review. However, we reported on withdrawal due to adverse events for the total population. Most withdrawals were due to adverse reactions to drug infusion. Withdrawal due to adverse events - 16 more people out of 100 withdrew from treatment with biweekly pegloticase compared with placebo (16% more withdrawals). - 17 more people out of 100 withdrew from treatment with monthly pegloticase compared to placebo (17% more withdrawals). - 18 people out of 100 withdrew from treatment with biweekly pegloticase due to adverse events. - 19 people out of 100 withdrew from treatment with monthly pegloticase due to adverse events. - 2 people out of 100 withdrew from treatment with placebo due to adverse events. Moderate-quality evidence indicated that pegloticase biweekly or monthly probably resolves one or more tophi. However, this has to be weighed up against high withdrawal rates from treatment due to adverse events, mostly due to an increase in infusion reactions. Pain reduction, quality of life, serum urate normalisation and function were not reported separately in people with tophi. The evidence was downgraded due to imprecise results. Further research may change these results. We do not know if other interventions, including surgery, are effective, as we found no randomised controlled trials that assessed other interventions."
    },
    {
        "index": "cochrane-simplification-test-354",
        "sentence": "The search identified five studies on oral immunoglobulin for the prevention of NEC of which three met the inclusion criteria. In this review of the three eligible trials (including 2095 neonates), the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC (typical risk ratio (RR) 0.84, 95% confidence interval (CI) 0.57 to 1.25; typical risk difference (RD) -0.01, 95% CI -0.03 to 0.01; 3 studies, 1840 infants), suspected NEC (RR 0.84, 95% CI 0.49 to 1.46; RD -0.01, 95% CI -0.02 to 0.01; 1 study, 1529 infants), need for surgery (typical RR 0.21, 95% CI 0.02 to 1.75; typical RD -0.03, 95% CI -0.06 to 0.00; 2 studies, 311 infants) or death from NEC (typical RR 1.10, 95% CI 0.47 to 2.59; typical RD 0.00, 95% CI -0.01 to 0.01; 3 studies, 1840 infants). Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomized controlled trials of oral IgA alone for the prevention of NEC.",
        "gold": "We searched the medical literature through January 2016 and found three randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) (with 2095 newborn infants). Treatment was started either in the first 24 hours following birth (two small studies) or following commencement of oral feeding (enteral) (one large well-controlled study). In this large study, infants generally received breast milk, whereas they received formula milk in the other two studies. Giving immunoglobulin (IgG alone or IgG plus IgA combination) did not reduce the incidence of NEC, need for surgery related to NEC or death from NEC, either during or after the study period. Immunoglobulins could possibly cause breakdown of red blood cells (called haemolysis) (red blood cells are common cells in the blood that delivery oxygen to organs), but no clinically important haemolysis was apparent. There were no other reported side effects. There was low-very low evidence for all the major outcomes. The major factor that affected the quality of evidence was the lack of precision in the result estimates, as the calculated plausible range of the effects (the 95% confidence intervals) were wide."
    },
    {
        "index": "cochrane-simplification-test-355",
        "sentence": "Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly favouring the addition of postoperative platinum based chemotherapy. The HR for progression-free survival is 0.75 (0.64 to 0.89). This means that chemotherapy reduces the risk of being dead at any censorship by a quarter. Chemotherapy reduces the risk of developing the first recurrence outside the pelvis (RR = 0.79 (0.68 to 0.92), 5% absolute risk reduction; NNT = 20). The analysis of pelvic recurrence rates is underpowered but the trend suggests that chemotherapy may be less effective than radiotherapy in a direct comparison (RR = 1.28 (0.97 to 1.68)) but it may have added value when used with radiotherapy (RR = 0.48 (0.20 to 1.18)). Postoperative platinum based chemotherapy is associated with a small benefit in progression-free survival and overall survival irrespective of radiotherapy treatment. It reduces the risk of developing a metastasis, could be an alternative to radiotherapy and has added value when used with radiotherapy.",
        "gold": "Womb (uterine/endometrial) cancer is a fairly common disease affecting approximately 1 in 70 women. A hysterectomy is usually curative because most cancers have a low risk of spreading (metastasising) to other sites which may result in a later recurrence. Microscopic examination of the hysterectomy specimen can tell doctors if there is a high risk of the cancer returning and this allows women to decide if they want further preventative treatment (adjuvant therapy) to reduce the risk. Chemotherapy can increase cure rates for other types of high-risk cancer after initial surgery and this review examines the effectiveness of chemotherapy for primary womb cancer after hysterectomy. Data from nine high quality randomised clinical trials involving up to 2197 women were subjected to systematic statistical modelling. This shows that chemotherapy reduces the risk of recurrent disease, lengthens the duration women have before a metastasis is diagnosed and improves survival rates. There are many ways to examine the data. The subset analysis that excluded old fashioned drug regimens suggests that chemotherapy reduces the risk of being dead at any nominated time by a quarter. The number of women who would need to have need chemotherapy to prevent one death depends on the type of cancer. In these trials, one woman was cured for every 25 women treated with high dose platinum based chemotherapy after hysterectomy. This is an absolute risk reduction of 4%. Chemotherapy is associated with a greater survival advantage than radiotherapy and has added value when used with radiotherapy. It also appears to reduce the absolute risk of developing a recurrence outside the pelvis by about 5%. This would benefit one woman in every 20 treated. However, chemotherapy has side effects, risks and temporarily reduces a woman's quality of life. In many cases, the small reduction in the cancer recurrence risk may not be worth the side effects of adjuvant treatment."
    },
    {
        "index": "cochrane-simplification-test-356",
        "sentence": "We included 35 studies, from a wide range of countries on six continents. Nineteen studies were conducted in low- and middle-income settings and sixteen in high-income settings. Some of the studies explored the views of people who had experienced the interventions, whereas others were hypothetical in nature, asking what people felt they would like from a digital health intervention. The studies covered a range of digital targeted client communication, for example medication or appointment reminders, prenatal health information, support for smoking cessation while pregnant, or general sexual health information. Our synthesis showed that clients' experiences of these types of programmes were mixed. Some felt that these programmes provided them with feelings of support and connectedness, as they felt that someone was taking the time to send them messages (moderate confidence in the evidence). They also described sharing the messages with their friends and family (moderate confidence). However, clients also pointed to problems when using these programmes. Some clients had poor access to cell networks and to the internet (high confidence). Others had no phone, had lost or broken their phone, could not afford airtime, or had changed their phone number (moderate confidence). Some clients, particularly women and teenagers, had their access to phones controlled by others (moderate confidence). The cost of messages could also be a problem, and many thought that messages should be free of charge (high confidence). Language issues as well as skills in reading, writing, and using mobile phones could also be a problem (moderate confidence). Clients dealing with stigmatised or personal health conditions such as HIV, family planning, or abortion care were also concerned about privacy and confidentiality (high confidence). Some clients suggested strategies to deal with these issues, such as using neutral language and tailoring the content, timing, and frequency of messages (high confidence). Clients wanted messages at a time and frequency that was convenient for them (moderate confidence). They had preferences for different delivery channels (e.g. short message service (SMS) or interactive voice response) (moderate confidence). They also had preferences about message content, including new knowledge, reminders, solutions, and suggestions about health issues (moderate confidence). Clients' views about who sent the digital health communication could influence their views of the programme (moderate confidence). For an overview of the findings and our confidence in the evidence, please see the 'Summary of qualitative findings' tables. Our matrix shows that many of the trials assessing these types of programmes did not try to address the problems we identified, although this may have been a reporting issue. Our synthesis identified several factors that can influence the successful implementation of targeted client communication programmes using mobile devices. These include barriers to use that have equity implications. Programme planners should take these factors into account when designing and implementing programmes. Future trial authors also need to actively address these factors and to report their efforts in their trial publications.",
        "gold": "We included 35 studies from around the world. These studies showed that clients' experiences of these types of programmes were mixed. Some felt that these programmes provided them with feelings of support and connectedness, as they felt that someone was taking the time to send them messages (moderate confidence in the evidence). Others also described sharing the messages with their friends and family (moderate confidence). However, clients also pointed to problems when using these programmes. Some clients had poor access to cell networks and to the internet (high confidence). Others had no phone, had lost or broken their phone, could not afford airtime, or had changed their phone number (moderate confidence). Some clients, particularly women and teenagers, had their access to phones controlled by others (moderate confidence). The cost of messages could also be a problem, and many thought that messages should be free of charge (high confidence). Languages issues as well as clients' skills in reading, writing, and using mobile phones could also be a problem (moderate confidence). Clients dealing with stigmatised or personal health conditions such as HIV, family planning, or abortion care were concerned about privacy and confidentiality (high confidence). Some suggested strategies to deal with these issues, such as using neutral language and tailoring the content, timing, and frequency of messages (high confidence). Clients wanted messages at a time and frequency that was convenient for them (moderate confidence). They had preferences for different delivery channels (e.g. short message service (SMS) or interactive voice response) (moderate confidence). They also had preferences about message content, including new knowledge, reminders, solutions, and suggestions about health issues (moderate confidence). Clients' views about who sent the digital health communication could influence their views of the programme, and many people wanted a sender that they knew and trusted (moderate confidence). We searched for studies published before July 2017."
    },
    {
        "index": "cochrane-simplification-test-357",
        "sentence": "Twenty-three trials involving 2467 people were included. Comparing methadone versus any other pharmacological treatment, we observed no clinical difference between the two treatments in terms of completion of treatment, 16 studies 1381 participants, risk ratio (RR) 1.08 (95% confidence interval (CI) 0.97 to 1.21); number of participants abstinent at follow-up, three studies, 386 participants RR 0.98 (95% CI 0.70 to 1.37); degree of discomfort for withdrawal symptoms and adverse events, although it was impossible to pool data for the last two outcomes. These results were confirmed also when we considered the single comparisons: methadone with: adrenergic agonists (11 studies), other opioid agonists (eight studies), anxiolytic (two studies), paiduyangsheng (one study). Comparing methadone with placebo (two studies) more severe withdrawal and more drop-outs were found in the placebo group.   The results indicate that the medications used in the included studies are similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted. Data from literature are hardly comparable; programs vary widely with regard to the assessment of outcome measures, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long- acting opioids, can reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use.",
        "gold": "For a tapered dose treatment to reduce withdrawal symptoms, illicit opioids are replaced by methadone or another agent using decreasing doses up to 30 days under medical supervision. The review authors searched the medical literature and identified 23 controlled trials involving 2467 adult opioid users in various countries. Trial participants were randomised to receive methadone or another pharmacological treatment. The other treatments were adrenergic agonists such as lofexidine, partial opioid agonists such as buprenorphine, opioid agonists such as LAAM (levo-\u03b1-acetyl-methadol) and the anxiolytics chlordiazepoxide and buspirone. In the two studies that compared methadone with placebo, withdrawal symptoms were more severe and more people dropped out in the placebo group. The studies included in this review confirmed that slow tapering with temporary substitution of long- acting opioids, could reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use. The medications used in the included studies were similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted. The programs varied widely with regard to the assessment of outcome measures. Seventeen of the included trials were conducted in inpatient settings."
    },
    {
        "index": "cochrane-simplification-test-358",
        "sentence": "Nine studies (eight randomised controlled trials) involving 1109 participants met the inclusion criteria for the review. Antagonist-induced withdrawal is more intense but less prolonged than withdrawal managed with reducing doses of methadone, and doses of naltrexone sufficient for blockade of opioid effects can be established significantly more quickly with antagonist-induced withdrawal than withdrawal managed with clonidine and symptomatic medications. The level of sedation does not affect the intensity and duration of withdrawal, although the duration of anaesthesia may influence withdrawal severity. There is a significantly greater risk of adverse events with heavy, compared to light, sedation (RR 3.21, 95% CI 1.13 to 9.12, P = 0.03) and probably with this approach compared to other forms of detoxification. Heavy sedation compared to light sedation does not confer additional benefits in terms of less severe withdrawal or increased rates of commencement on naltrexone maintenance treatment. Given that the adverse events are potentially life-threatening, the value of antagonist-induced withdrawal under heavy sedation or anaesthesia is not supported. The high cost of anaesthesia-based approaches, both in monetary terms and use of scarce intensive care resources, suggest that this form of treatment should not be pursued.",
        "gold": "The review of trials shows that this sort of withdrawal treatment is quicker than withdrawal managed with reducing doses of methadone or clonidine plus symptomatic medications. The intensity of withdrawal experienced with anaesthesia-based approaches is similar to that experienced with approaches using only minimal sedation, but there is a significantly increased risk of serious adverse events with anaesthesia-assisted approaches. The lack of additional benefit, and increased risk of harm, suggest that this form of treatment should not be pursued."
    },
    {
        "index": "cochrane-simplification-test-359",
        "sentence": "We included fourteen studies. Duration ranged from very short (10 days) studies of the intramuscular preparation, to trials lasting over three months. For measures of global assessment, available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics we found no evidence of a difference in effectiveness (doctors' 4 RCTs n=150, RR 1.13, CI 0.69 to 1.86; nurses 4RCTs n=146, RR 1.23, CI 0.82 to 1.86). Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). The strength of the evidence relating to this compound is limited, owing to small sample size, poor study design, limited outcomes and incomplete reporting. Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). Data from this review suggest, at present, there is no evidence to suggest that it may have an atypical profile.",
        "gold": "We included fourteen randomised controlled trials. When compared to other typical antipsychotics molindone shows no difference in effectiveness and is no more or less likely than typical drugs to cause movement disorders, it does however cause significantly more weight loss. At present there is no evidence to suggest that it may have an atypical profile."
    },
    {
        "index": "cochrane-simplification-test-360",
        "sentence": "We included 20 studies with a total of 2125 participants covering 23 different treatments. Statistical pooling of the data was not possible due to the heterogeneity of treatments. Each study involved a different set of interventions.\u00a0They can be grouped into those including a bleaching agent such as hydroquinone, triple-combination creams (hydroquinone, tretinoin, and fluocinolone acetonide), and combination therapies (hydroquinone cream and glycolic acid peels), as well as less conventional therapies including rucinol, vitamin C iontophoresis, and skin-lightening complexes like Thiospot and Gigawhite. Triple-combination cream was significantly more effective at lightening melasma than hydroquinone alone (RR 1.58, 95% CI 1.26 to 1.97) or when compared to the dual combinations of tretinoin and hydroquinone (RR 2.75, 95% CI 1.59 to 4.74), tretinoin and fluocinolone acetonide (RR 14.00, 95% CI 4.43 to 44.25), or hydroquinone and fluocinolone acetonide (RR 10.50, 95% CI 3.85 to 28.60). Azelaic acid (20%) was significantly more effective than 2% hydroquinone (RR 1.25, 95% CI 1.06 to 1.48) at lightening melasma but not when compared to 4% hydroquinone (RR 1.11, 95% CI 0.94 to 1.32). In two studies where tretinoin was compared to placebo, participants rated their melasma as significantly improved in one (RR 13, 95% CI 1.88 to 89.74) but not the other. In both studies by other objective measures tretinoin treatment significantly reduced the severity of melasma. Thiospot was more effective than placebo (SMD -2.61, 95% CI -3.76 to -1.47). The adverse events most commonly reported were mild and transient such as skin irritation, itching, burning, and stinging. The quality of studies evaluating melasma treatments was generally poor and available treatments inadequate. High-quality randomised controlled trials on well-defined participants with long-term outcomes to determine the duration of response are needed.",
        "gold": "We included 20 studies with a total of 2125 participants covering 23 different treatments. Triple-combination cream was significantly more effective at lightening melasma when compared to hydroquinone alone or to dual combinations such as tretinoin and hydroquinone, tretinoin and fluocinolone acetonide, or hydroquinone and fluocinolone acetonide. Tretinoin was more effective at lightening melasma compared to placebo, as was the skin-whitening complex Thiospot. However, many studies were of a poor quality with a only small number of participants. The side-effects reported most frequently by both participants and clinicians were dry, red, and sore skin. No serious side-effects were seen. More evidence is needed on other treatments which are widely used, including the role of sunscreens which were recommended in almost all studies. There is a need for high-quality studies comparing the treatments for this difficult to manage condition. For example, studies should have a minimum follow-up period of 6 months and should clearly categorise participant groups such as age, type of melasma, and duration of the condition at the start of the trial so that these differences can be considered when assessing results. Addtionally, study outcomes should include participants' views in a standardised manner because they may perceive the degree of skin lightening differently to the trial investigators."
    },
    {
        "index": "cochrane-simplification-test-361",
        "sentence": "Twelve trials, which randomised 1319 participants, were included in the review. As far as can be determined from the trial reports, the methodological quality of the trials was not high, including a high risk of detection bias in many. Of note, only one study reported low-dose postoperative 5-FU and this paper was at high risk of reporting bias. Not all studies reported population characteristics, of those that did mean age ranged from 61 to 75 years. 83% of participants were white and 40% were male. All studies were a minimum of one year long. A significant reduction in surgical failure in the first year after trabeculectomy was detected in eyes at high risk of failure and those undergoing surgery for the first time receiving regular-dose 5-FU postoperative injections (RR 0.44, 95% confidence interval (CI) 0.29 to 0.68 and 0.21, 0.06 to 0.68, respectively). No surgical failures were detected in studies assessing combined surgery. No difference was detected in the low-dose postoperative 5-FU injection group in patients undergoing primary trabeculectomy (RR 0.93, 95% CI 0.70 to 1.24). Peroperative 5-FU in patients undergoing primary trabeculectomy significantly reduced risk of failure (RR 0.67, 95% CI 0.51 to 0.88). This translates to a number needed to treat for an additional beneficial outcome of 4.1 for the high risk of failure patients, and 5.0 for primary trabeculectomy patients receiving postoperative 5-FU. Intraocular pressure was also reduced in the primary trabeculectomy group receiving intraoperative 5-FU (mean difference (MD) -1.04, 95% CI -1.65 to -0.43) and regular-dose postoperative 5-FU (MD -4.67, 95% CI -6.60 to -2.73). No significant change occurred in the primary trabeculectomy group receiving low-dose postoperative 5-FU (MD -0.50, 95% CI -2.96 to 1.96). Intraocular pressure was particularly reduced in the high risk of failure population receiving regular-dose postoperative 5-FU (MD -16.30, 95% CI -18.63 to -13.97). No difference was detected in the combined surgery population receiving regular-dose postoperative 5-FU (MD -1.02, 95% CI -2.40 to 0.37). Whilst no evidence was found of an increased risk of serious sight-threatening complications, other complications are more common after 5-FU injections. None of the trials reported on the participants' perspective of care. The quality of evidence varied between subgroups and outcomes, most notably the evidence for combined surgery and low-dose postoperative 5-FU was found to be very low using GRADE. The combined surgery postoperative 5-FU subgroup because no surgical failures have been reported and the sample size is small (n = 118), and the low-dose postoperative 5-FU group because of the small sample size (n = 76) and high risk of bias of the only contributing study. Postoperative injections of 5-FU are now rarely used as part of routine packages of postoperative care but are increasingly used on an ad hoc basis. This presumably reflects an aspect of the treatment that is unacceptable to both patients and doctors. None of the trials reported on the participants' perspective of care, which constitutes a serious omission for an invasive treatment such as this. The small but statistically significant reduction in surgical failures and intraocular pressure at one year in the primary trabeculectomy group and high-risk group must be weighed against the increased risk of complications and patient preference.",
        "gold": "This is a summary of a Cochrane review that looked at the effect of using one of these drugs, 5-Fluorouracil (5-FU). We gathered evidence from 12 trials involving 1319 participants. The evidence is current to July 2013. For patients who have never had eye surgery before, 5-FU injections after surgery can slightly reduce the pressure in the eye after one year and also the risk of having more surgery in the first year. For patients having both cataract surgery and glaucoma surgery at the same time, no difference has been detected between injections and no injections. Some people are at higher risk of having problems following trabeculectomy, for instance people that have had previous surgery on the eye. For this group, the 5-FU injections can reduce the pressure in the eye a little and also reduce the risk of having more surgery in the first year. Only one study has investigated the effect of using lower than normal doses in the injections. No benefit was found when compared to a control group who had no injections. If 5-Fluorouracil was applied to the eye during the surgery, there was less chance of having to have more surgery within the year and the pressure in the eye was also reduced slightly at one year. Complications such as damage to cells at the front of the eye or a leak from the wound seem more common when 5-FU is used. The methodological quality of the trials was not high in general. In many of the studies that contributed to the evidence about 5-FU after glaucoma surgery the researchers were aware of whether the participant had received the dummy injection or the 5-FU injection. This may have introduced bias into the results. Importantly the only study contributing information about low dose 5-FU was of low methodological quality so our conclusions on low dose 5-FU must be cautious. The studies that contributed evidence about 5-FU during surgery was largely very good, the studies were designed and reported to a standard we would expect of modern trials. We concluded that the main benefit is for people at high risk of problems. There may be a smaller benefit for people at low risk of problems if 5-FU is given either as injections after surgery or during the operation. However, 5-FU was found to increase the risk of serious complications and so may not be worthwhile for the small benefit gained."
    },
    {
        "index": "cochrane-simplification-test-362",
        "sentence": "Fifty-five primary studies with 16,154 participants met the inclusion criteria. Long-term use of ICS (more than six months) did not consistently reduce the rate of decline in forced expiratory volume in one second (FEV1) in COPD patients (generic inverse variance analysis: mean difference (MD) 5.80 mL/year with ICS over placebo, 95% confidence interval (CI) -0.28 to 11.88, 2333 participants; pooled means analysis: 6.88 mL/year, 95% CI 1.80 to 11.96, 4823 participants), although one major trial demonstrated a statistically significant difference. There was no statistically significant effect on mortality in COPD patients (odds ratio (OR) 0.98, 95% CI 0.83 to 1.16, 8390 participants). Long-term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: MD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14, 2586 participants; pooled means analysis: MD -0.19 exacerbations per patient per year, 95% CI -0.30 to -0.08, 2253 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (MD -1.22 units/year, 95% CI -1.83 to -0.60, 2507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.65, 95% CI 2.03 to 3.46, 5586 participants) and hoarseness. In the long-term studies, the rate of pneumonia was increased in the ICS group compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.56, 95% CI 1.30 to 1.86, 6235 participants). The long-term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over three years. Patients and clinicians should balance the potential benefits of inhaled steroids in COPD (reduced rate of exacerbations, reduced rate of decline in quality of life and possibly reduced rate of decline in FEV1) against the potential side effects (oropharyngeal candidiasis and hoarseness, and risk of pneumonia).",
        "gold": "Pooling of the data from the 55 trials with 16,154 people showed that there was no consistent long-term benefit in the rate of decline in breathing capacity. Death rates were unchanged. Inhaled steroids were beneficial in slowing down the rate of decline in quality of life and reducing the frequency of exacerbations. Inhaled steroids increased the risk of side effects including thrush (candida) infection in the mouth and hoarseness, and the rate of pneumonia. In deciding whether to use this treatment, consumers and health professionals should weigh up the benefits (reduced rate of exacerbations, reduced decline in quality of life and possible reduction in the rate of decline of breathing capacity) against the side effects (mouth thrush, hoarseness and increased risk of developing pneumonia)."
    },
    {
        "index": "cochrane-simplification-test-363",
        "sentence": "We included 80 randomised controlled trials (5820 women). They compared 20 different NSAIDs (18 non-selective and two COX-2-specific) versus placebo, paracetamol or each other. NSAIDs versus placebo Among women with primary dysmenorrhoea, NSAIDs were more effective for pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09; 35 RCTs, I2 = 53%, low quality evidence). This suggests that if 18% of women taking placebo achieve moderate or excellent pain relief, between 45% and 53% taking NSAIDs will do so. However, NSAIDs were associated with more adverse effects (overall adverse effects: OR 1.29, 95% CI 1.11 to 1.51, 25 RCTs, I2 = 0%, low quality evidence; gastrointestinal adverse effects: OR 1.58, 95% CI 1.12 to 2.23, 14 RCTs, I2 = 30%; neurological adverse effects: OR 2.74, 95% CI 1.66 to 4.53, seven RCTs, I2 = 0%, low quality evidence). The evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so. NSAIDs versus other NSAIDs When NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain relief or safety. However, the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials. Non-selective NSAIDs versus COX-2-specific selectors Only two of the included studies utilised COX-2-specific inhibitors (etoricoxib and celecoxib). There was no evidence that COX-2-specific inhibitors were more effective or tolerable for the treatment of dysmenorrhoea than traditional NSAIDs; however data were very scanty. NSAIDs versus paracetamol NSAIDs appeared to be more effective for pain relief than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, three RCTs, I2 = 0%, low quality evidence). There was no evidence of a difference with regard to adverse effects, though data were very scanty. Most of the studies were commercially funded (59%); a further 31% failed to state their source of funding. NSAIDs appear to be a very effective treatment for dysmenorrhoea, though women using them need to be aware of the substantial risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea. We rated the quality of the evidence as low for most comparisons, mainly due to poor reporting of study methods.",
        "gold": "We found 80 randomised controlled trials (RCTs), which included a total of 5820 women and compared 20 different types of NSAIDs with placebo (an inactive pill), paracetamol or each other. Most of the studies were commercially funded (59%), and a further 31% did not state their source of funding. The review found that NSAIDs appear to be very effective in relieving period pain. The evidence suggests that if 18% of women taking placebo achieve moderate or excellent pain relief, between 45% and 53% taking NSAIDs will do so. NSAIDs appear to work better than paracetamol, but it is unclear whether any one NSAID is safer or more effective than others. NSAIDs commonly cause adverse effects (side effects), including indigestion, headaches and drowsiness. The evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so. Based on two studies that made head-to-head comparisons, there was no evidence that newer types of NSAID (known as COX-2-specific inhibitors) are more effective for the treatment of dysmenorrhoea than traditional NSAIDs (known as non-selective inhibitors), nor that there is a difference between them with regard to adverse effects. We rated the quality of the evidence as low for most comparisons, mainly due to poor reporting of study methods."
    },
    {
        "index": "cochrane-simplification-test-364",
        "sentence": "We included seven studies that compared high versus low levels of PEEP (2565 participants). In five of the studies (2417 participants), a comparison was made between high and low levels of PEEP with the same tidal volume in both groups, but in the remaining two studies (148 participants), the tidal volume was different between high- and low-level groups. We saw evidence of risk of bias in three studies, and the remaining studies fulfilled all criteria for adequate trial quality. In the main analysis, we assessed mortality occurring before hospital discharge only in those studies that compared high versus low PEEP with the same tidal volume in both groups. With the three studies that were included, the meta-analysis revealed no statistically significant differences between the two groups (relative risk (RR) 0.90, 95% confidence interval (CI) 0.81 to 1.01), nor was any statistically significant difference seen in the risk of barotrauma (RR 0.97, 95% CI 0.66 to 1.42). Oxygenation was improved in the high-PEEP group, although data derived from the studies showed a considerable degree of statistical heterogeneity. The number of ventilator-free days showed no significant difference between the two groups. Available data were insufficient to allow pooling of length of stay in the intensive care unit (ICU). The subgroup of participants with ARDS showed decreased mortality in the ICU, although it must be noted that in two of the three included studies, the authors used a protective ventilatory strategy involving a low tidal volume and high levels of PEEP. Available evidence indicates that high levels of PEEP, as compared with low levels, did not reduce mortality before hospital discharge. The data also show that high levels of PEEP produced no significant difference in the risk of barotrauma, but rather improved participants' oxygenation to the first, third, and seventh days. This review indicates that the included studies were characterized by clinical heterogeneity.",
        "gold": "In this Cochrane review, we assess the benefits and harms of high versus low levels of PEEP in patients with ALI and ARDS. The undertaking of this review was both relevant and necessary because the optimal level of PEEP in these patients is still controversial, and available evidence indicates no difference in mortality. We included seven studies involving a total of 2565 participants and found that high levels of PEEP, as compared with low levels, did not produce a reduction in hospital mortality, although we did see a trend towards decreased mortality. We also found evidence of clinical heterogeneity among the included studies (clinical heterogeneity concerns differences in participants, interventions, and outcomes that might have an impact on results from the use of PEEP). The studies included were of moderate to good quality. We did not find a significant difference with respect to barotrauma\u2014defined as the presence of pneumothorax on chest radiography or a chest tube insertion for known or suspected pneumothorax. We furthermore ascertained that high levels of PEEP improved participants' oxygenation up to the first, third, and seventh days. The number of ventilator-free days showed no significant difference between the two groups (the term ventilator-free days refers to the number of days between successful weaning from mechanical ventilation and day 28 after study enrolment), and available data were insufficient to allow pooling of lengths of stay in the intensive care unit. Additional trials will be required to determine which patients should receive high PEEP levels and the best means of applying this intervention."
    },
    {
        "index": "cochrane-simplification-test-365",
        "sentence": "This review included 42 studies (11,399 patients) including 19 studies from the original review (2010), as well as 23 new studies. Fifteen studies were excluded from the original review (nine retracted from publication due to concerns about integrity of data and six lacking individual patient creatinine data for the calculation of RIFLE criteria). Overall, there was a significant increase in the need for RRT in the HES treated individuals compared to individuals treated with other fluid therapies (RR 1.31, 95% CI 1.16 to 1.49; 19 studies, 9857 patients) and the number with author-defined kidney failure (RR 1.59, 95% CI 1.26 to 2.00; 15 studies, 1361 patients). The RR of AKI based on RIFLE-F (failure) criteria also showed an increased risk of AKI in individuals treated with HES products (RR 1.14, 95% CI 1.01 to 1.30; 15 studies, 8402 participants). The risk of meeting urine output and creatinine based RIFLE-R (risk) criteria for AKI was in contrast in favour of HES therapies (RR 0.95, 95% CI 0.91 to 0.99; 20 studies, 8769 patients). However, when RIFLE-R urine output based outcomes were excluded as per study protocol, the direction of AKI risk again favoured the other fluid type, with a non-significant RR of AKI in HES treated patients (RR 1.05, 95% CI 0.97 to 1.14; 8445 patients). A more robust effect was seen for the RIFLE-I (injury) outcome, with a RR of AKI of 1.22 (95% CI 1.08 to 1.37; 8338 patients). No differences between subgroups for the RRT and RIFLE-F based outcomes were seen between sepsis versus non-sepsis patients, high molecular weight (MW) and degree of substitution (DS) versus low MW and DS (\u2265 200 kDa and > 0.4 DS versus 130 kDa and 0.4 DS) HES solutions, or high versus low dose treatments (i.e. \u2265 2 L versus < 2 L). There were differences identified between sepsis versus non-sepsis subgroups for the RIFLE-R and RIFLE-I based outcomes only, which may reflect the differing renal response to fluid resuscitation in pre-renal versus sepsis-associated AKI. Overall, methodological quality of the studies was good. The current evidence suggests that all HES products increase the risk in AKI and RRT in all patient populations and a safe volume of any HES solution has yet to be determined. In most clinical situations it is likely that these risks outweigh any benefits, and alternate volume replacement therapies should be used in place of HES products.",
        "gold": "This review examined the effects of HES on kidney function compared to other fluid therapies in critically ill patients. Forty-two randomised clinical trials (11,399 patients) comparing HES to another fluid therapy qualified for this review. Overall, the use of HES products was associated with a 59% increased risk of kidney failure, and a 32% increased risk of dialysis. No significant differences in effect were seen depending on the patient population studied, the type of HES solution, or the dose used. Due to the potential risks associated with HES products, alternative fluid therapies should be used."
    },
    {
        "index": "cochrane-simplification-test-366",
        "sentence": "We identified nine studies that enrolled 682 participants. None of the studies reported blinding or group allocation methods. Seven studies were judged to be at low risk of incomplete outcome reporting; three studies were judged to be a low risk of selective reporting (protocols were available and/or all outcomes relevant to the this review were reported); and two studies were judged free of other potential biases. Seven studies compared Rheum officinale with no treatment and two made comparisons with captopril, an angiotensin-converting enzyme inhibitor (ACEi). Compared with no treatment, Rheum officinale had a positive effect on SCr (MD -87.49 \u00b5mol/L, 95% CI -139.25 to -35.72) and BUN (MD -10.61 mmol/L, 95% CI -19.45 to -2.21). Compared with captopril, a statistically significant difference was not demonstrated in relation to Rheum officinale for any outcome (BUN, CrCl, or patients' capacity to undertake work). No data were available on all-cause mortality or cost of treatment. Only minor adverse events were reported in association with Rheum officinale. Currently available evidence concerning the efficacy of Rheum officinale to improve SCr and BUN levels in patients with CKD is both scant and low quality. Although Rheum officinale does not appear to be associated with serious adverse events among patients with CKD, there is no current evidence to support any recommendation for its use.",
        "gold": "We analysed evidence from nine studies conducted in China that compared Rheum officinale with no treatment or treatment with captopril, an ACEi. We looked at reported changes in two important blood markers - serum creatinine and blood urea nitrogen - that indicate progression of CKD. We found no high quality evidence to indicate that treatment with Rheum officinale can improve CKD or delay its progression. Rheum officinale was not found to cause any serious health problems in patients with CKD. Well-designed randomised controlled studies are needed to provide robust, high quality evidence to assess if there are benefits from Rheum officinale for people with CKD."
    },
    {
        "index": "cochrane-simplification-test-367",
        "sentence": "From 72 papers describing IQCODE test accuracy, we included 13 papers, representing data from 2745 individuals (n = 1413 (51%) with dementia). Pooled analysis of all studies using data presented closest to a cut-off of 3.3 indicated that sensitivity was 0.91 (95% CI 0.86 to 0.94); specificity 0.66 (95% CI 0.56 to 0.75); the positive likelihood ratio was 2.7 (95% CI 2.0 to 3.6) and the negative likelihood ratio was 0.14 (95% CI 0.09 to 0.22). There was a statistically significant difference in test accuracy between the general hospital setting and the specialist memory setting (P = 0.019), suggesting that IQCODE performs better in a 'general' setting. We found no significant differences in the test accuracy of the short (16-item) versus the 26-item IQCODE, or in the language of administration. There was significant heterogeneity in the included studies, including a highly varied prevalence of dementia (10.5% to 87.4%). Across the included papers there was substantial potential for bias, particularly around sampling of included participants and selection criteria, which may limit generalisability. There was also evidence of suboptimal reporting, particularly around disease severity and handling indeterminate results, which are important if considering use in clinical practice. The IQCODE can be used to identify older adults in the general hospital setting who are at risk of dementia and require specialist assessment; it is useful specifically for ruling out those without evidence of cognitive decline. The language of administration did not affect test accuracy, which supports the cross-cultural use of the tool. These findings are qualified by the significant heterogeneity, the potential for bias and suboptimal reporting found in the included studies.",
        "gold": "We searched electronic databases of published research studies, looking for all studies of IQCODE in a hospital setting. We searched from the first available papers in scientific databases up to and including January 2013. We found 13 relevant studies which had results suitable to be combined in a single analysis. Of these papers, six (1352 participants) described studies conducted in \u201cspecialist\u201d services such as memory clinics or wards. Three papers (566 participants) described studies conducted in general older adult services and four studies (827 participants) included both specialist and general services. Summarising the available papers, we found that IQCODE was useful for 'ruling out' possible dementia in the general hospital setting. This means if a person has a low score on IQCODE testing they probably do not have dementia. IQCODE was less useful in specialist memory clinics and psychiatry wards. We also found that a short version of the IQCODE gave similar results to the traditional longer version. As part of our assessment we looked at whether the design of the available studies was suitable for the study question. We found several instances where the design of the study could be improved. For example, seven of the thirteen studies only included a selection of all the people attending the service who could have been assessed with IQCODE. We also looked at how well researchers reported the conduct and results of their studies. Again, there were many instances where the reporting could be improved. A common issue was not describing the severity of memory and thinking problems in those thought to have dementia, only reported in three of the included studies. In summary, IQCODE may be a useful tool for assessing adults for possible dementia. There are still a number of unanswered questions around how useful IQCODE may be in hospital settings. For example, before we start using IQCODE routinely we need to describe if it is practical and acceptable to hospital staff, to patients and to their carers. The review was performed by a team based in research centres in the UK (Glasgow, Leicester, Oxford). We had no external funding specific to this study and we have no conflicts of interest that may have influenced our assessment of the research data."
    },
    {
        "index": "cochrane-simplification-test-368",
        "sentence": "We included three RCTs involving 91 participants. All three studies scored 'low quality' on the methodological quality assessment, implying high risk of bias.\u00a0All studies investigated various types and intensities of outpatient rehabilitation programmes following BoNT for upper limb spasticity in adults with chronic stroke. Rehabilitation programmes included: modified constraint-induced movement therapy (mCIMT) compared with a neurodevelopmental therapy programme; task practice therapy with cyclic functional electrical stimulation (FES) compared with task practice therapy only; and occupational, manual therapy with dynamic elbow extension splinting compared with occupational therapy only. There was 'low quality' evidence for mCIMT improving upper limb motor function and spasticity in chronic stroke survivors with residual voluntary upper limb activity, up to six months, and 'very low quality' evidence for dynamic elbow splinting and occupational therapy reducing elbow range of movement at 14 weeks. Task practice therapy with cyclic FES did not improve upper limb function more than task practice therapy alone, only at 12 weeks. No studies addressed interventions in children and those with lower limb spasticity, or after other focal intramuscular treatments for spasticity. At best there was 'low level' evidence for the effectiveness of outpatient MD rehabilitation in improving active function and impairments following BoNT for upper limb spasticity in adults with chronic stroke.\u00a0No trials explored the effect of MD rehabilitation on 'passive function' (caring for the affected limb), caregiver burden, or the individual's priority goals for treatment. The optimal types (modalities, therapy approaches, settings) and intensities of therapy for improving activity (active and passive function) in adults and children with post-stroke spasticity, in the short and longer term, are unclear. Further research is required to build evidence in this area.",
        "gold": "We included three relevant studies in the review, which investigated different types of MD rehabilitation interventions after botulinum toxin injections into the arms of 91 adults with previous stroke. There was low quality evidence for intensive forced use of the affected arm in improving spasticity, and very low quality evidence for elbow splinting with occupational therapy. We did not identify any studies of MD rehabilitation in children with post-stroke spasticity or after other injected medications. The review findings are limited by the small number of studies that are methodologically flawed. More research is needed into what rehabilitation modalities and treatments are most effective for spasticity management following stroke."
    },
    {
        "index": "cochrane-simplification-test-369",
        "sentence": "Four trials, recruiting 136 participants, were included. Two trials compared lamivudine alone versus HBIg alone. Randomisation was performed one week after transplantation in one of the trials and after six months after transplantation in another; from transplantation until randomisation, HBIg alone was given to all patients in the two trials. A third trial compared combination treatment with lamivudine and HBIg versus lamivudine alone after one month of combination treatment, and a fourth trial compared the combination of lamivudine and HBIg versus a combination of lamivudine and adefovir dipivoxil after at least 12-month of lamivudine and HBIg combination treatment. Statistically significant differences were not detected in any of the comparisons and outcomes. All trials were open-labelled, and none of the trials were adequately powered to show a difference in HBV recurrence. No meta-analyses were performed since the identified trials assessed different comparisons. This review could not derive clear evidence from randomised clinical trials for the treatment of patients with chronic HBV following liver transplantation for preventing recurrence of HBV infection. Large randomised clinical trials comparing long-term combination treatment to each of the monotherapy alone, including the newer antiviral drugs, are needed.",
        "gold": "We found only four randomised clinical trials that compared different prophylactic regimens in 136 participants. None of the trials compared the same prophylaxis regimen. In each individual trial no significant differences were detected with regard to patients' survival after transplantation, HBV recurrence, or the recurrence of liver disease. All trials were too small to detect a difference, if it existed. Prevention of HBV recurrence following liver transplantation is currently non-evidence based. Practice is to administer a combination of HBIg and an antiviral drug. Randomised clinical trials are needed to examine this practice."
    },
    {
        "index": "cochrane-simplification-test-370",
        "sentence": "Searches identified 13,306 citations. Fifteen publications (ten studies) were included, involving 1019 participants who were followed between three months to 10 years (1060 randomised). All studies had a high risk of bias. Sulphonylurea (SU) with insulin did not improve metabolic control significantly more than insulin alone at three months (one study, n = 15) and at 12 months (one study, n = 14) of treatment and follow-up. SU (with or without metformin) gave poorer metabolic control compared to insulin alone (mean difference in glycosylated haemoglobin A1c (HbA1c) from baseline to end of study, for insulin compared to oral therapy: -1.3% (95% confidence interval (CI) -2.4 to -0.1; P = 0.03, 160 participants, four studies, follow-up/duration of therapy: 12, 30, 36 and 60 months; however, heterogeneity was considerable). In addition, there was evidence that SU caused earlier insulin dependence (proportion requiring insulin at two years was 30% in the SU group compared to 5% in conventional care group (P < 0.001); patients classified as insulin dependent was 64% (SU group) and 12.5% (insulin group, P = 0.007). No intervention influenced fasting C-peptide, but insulin maintained stimulated C-peptide better than SU (one study, mean difference 7.7 ng/ml (95% CI 2.9 to 12.5)). In a five year follow-up of GAD65 (glutamic acid decarboxylase formulated with aluminium hydroxide), improvements in fasting and stimulated C-peptide levels (20 \u03bcg group) were maintained after five years. Short term (three months) follow-up in one study (n = 74) using Chinese remedies did not demonstrate a significant difference in improving fasting C-peptide levels compared to insulin alone (0.07 \u00b5g/L (95% CI -0.05 to 0.19). One study using vitamin D with insulin showed steady fasting C-peptide levels in the vitamin D group but declining fasting C-peptide levels (368 to 179 pmol/L, P = 0.006) in the insulin alone group at 12 months follow-up. Comparing studies was difficult as there was a great deal of heterogeneity in the studies and in their selection criteria. There was no information regarding health-related quality of life, complications of diabetes, cost or health service utilisation, mortality and limited evidence on adverse events (studies on oral agents or insulin reported no adverse events in terms of severe hypoglycaemic episodes). Two studies show SU leading to earlier insulin dependence and a meta-analysis of four studies with considerable heterogeneity showed poorer metabolic control if SU is prescribed for patients with LADA compared to insulin. One study showed that vitamin D with insulin may protect pancreatic beta cells in LADA. Novel treatments such as GAD65 in certain doses (20 \u03bcg) have been suggested to maintain fasting and stimulated C-peptide levels. However, there is no significant evidence for or against other lines of treatment of LADA.",
        "gold": "We identified 15 publications (10 studies) looking at 1019 patients who were followed between three months to 10 years. We found many of the publications had poor quality of reporting and had small numbers of participants. However, there does seem to be evidence from this review that the drug sulphonylurea (like glibenclamide or glyburide, gliclazide) could make patients insulin dependent sooner and it does not control blood sugar as well as insulin. Therefore, this suggests that this drug should not be a first line treatment for patients with LADA. In addition, insulin combined with vitamin D, or Chinese herbs may maintain natural insulin production better than insulin alone. Similarly, glutamic acid decarboxylase (GAD65) may maintain natural insulin production. However, there was no conclusive evidence that any of the other remaining treatment methods were better than each other. Studies on oral agents or insulin reported no adverse events in terms of severe hypoglycaemic attacks. This review represents very early days of our understanding of the best way to treat LADA. It is limited by the poor reporting quality of the studies, small sample sizes, no clear single definition of LADA and many of the studies being carried out in different ethnic groups (China, Japan, Cuba, UK, Sweden) with different clinical care systems.  None of the publications reported on complications of diabetes, health-related quality of life, costs or health service utilisation. All but one of the publications reported there were no deaths.  In summary, this review demonstrates that insulin treatment may be preferable compared to sulphonylurea treatment but there is little evidence regarding other forms of treatment. Future studies are needed, should have a clear definition of LADA, investigate patient-important outcomes and use a common method of measuring stimulated C-peptide (a marker of natural insulin production reflecting improved beta-cell function of the pancreas)."
    },
    {
        "index": "cochrane-simplification-test-371",
        "sentence": "A total of 70 studies (44,958 participants) were included in the review, and 63 studies (42,784 participants) in the meta-analyses. Overall, the risk of bias assessment showed that these studies provided moderate or low quality evidence. Outcomes at four or more months post-intervention were of particular interest to assess when effects were sustained beyond the immediate short term. We have reported pooled effects across delivery modes only for those analyses for which heterogeneity across delivery modes is not substantial (I2 < 50%). Alcohol-related problems at four or more months: IFF standardised mean difference (SMD) -0.14, 95% confidence interval (CI) -0.24 to -0.04 (participants = 2327; studies = 11; moderate quality evidence), equivalent to a decrease of 1.28 points in the 69-point alcohol problems scale score. No effects were found for WF or MF. Binge drinking at four or more months: results pooled across delivery modes: SMD -0.06, 95% CI -0.11 to -0.02 (participants = 11,292; studies = 16; moderate quality evidence), equivalent to 2.7% fewer binge drinkers if 30-day prevalence is 43.9%. Drinking quantity at four or more months: results pooled across delivery modes: SMD -0.08, 95% CI -0.12 to -0.04 (participants = 21,169; studies = 32; moderate quality evidence), equivalent to a reduction of 0.9 drinks consumed each week, from a baseline of 13.7 drinks per week. Drinking frequency at four or more months: WF SMD -0.11, 95% CI -0.17 to -0.04 (participants = 9929; studies = 10; moderate quality evidence), equivalent to a decrease of 0.17 drinking days/wk, from a baseline of 2.74 days/wk; IFF SMD -0.21, 95% CI -0.31 to -0.10 (participants = 1464; studies = 8; moderate quality evidence), equivalent to a decrease of 0.32 drinking days/wk, from a baseline of 2.74 days/wk. No effects were found for GFF or MC. Estimated blood alcohol concentration (BAC) at four or more months: peak BAC results pooled across delivery modes: SMD -0.08, 95% CI -0.17 to 0.00 (participants = 7198; studies = 11; low quality evidence), equivalent to a reduction in peak BAC from an average of 0.144% to 0.135%. No effects were found for typical BAC with IFF. The results of this review indicate that no substantive meaningful benefits are associated with social norms interventions for prevention of alcohol misuse among college/university students. Although some significant effects were found, we interpret the effect sizes as too small, given the measurement scales used in the studies included in this review, to be of relevance for policy or practice. Moreover, the significant effects are not consistent for all misuse measures, heterogeneity was a problem in some analyses and bias cannot be discounted as a potential cause of these findings.",
        "gold": "70 studies were included in this review, with 44,958 students overall. We were interested mainly in studies with a follow-up period of four or more months to assess whether any effects were sustained beyond the immediate short term. In 43 of the trials, the social norms intervention was targeted at higher-risk students. 55 trials were conducted in the USA, with others form Australia, Brazil, New Zealand, Sweden and the United Kingdom. Delivery of social norms information included mailed feedback, web/computer feedback, individual face-to-face feedback, group face-to-face feedback and general social norms marketing campaigns across college campuses. Over the longer-term, after four or more months of follow-up, there was only a small effect of social norms information on binge drinking, drinking quantity, and peak BAC. For these outcomes, effects were not any different across the different delivery modes.Only small effects were found for web feedback and individual face-to-face feedback on frequency of alcohol consumed. Only a small effect of individual face-to-face feedback on alcohol related problems, but no effects were found for mailed or web feedback. Similarly, no effects were found for group face-to-face feedback or for marketing campaigns on frequency of alcohol consumed and typical BAC. Our reading of these results is that, although we found some significant effects of social norms information, the strength of the effects over the longer-term is very small and therefore this information is unlikely to provide any advantage in practice. Overall, only low or moderate quality evidence was noted for the effects reported in this review. Problems with study quality could result in estimates of social norms effects that are too high, so we cannot rule out the chance that the effects observed in this review may be overstated. The U.S. National Institutes of Health provided funding for just under half (33/70) of the studies included in this review. Eighteen studies provided no information about funding, and only 13 papers had a clear conflict of interest statement."
    },
    {
        "index": "cochrane-simplification-test-372",
        "sentence": "We included three trials with a total of 492 participants who had received 530 THA. The evidence presented with a high risk of performance, detection and reporting bias. One study (81 participants) compared outcomes for participants randomised to the provision of hip precautions, equipment and functional restrictions versus no provision of hip precautions, equipment or functional restrictions. Due to the quality of evidence being very low, we are uncertain if the provision of hip precautions, equipment and functional restrictions improved function measured using the Harris Hip Score at 12 month follow-up, or health-related quality of life (HRQOL) measured by the Short Form-12 at four week follow-up, compared to not providing this. There were no incidences of hip dislocation or adverse events in either group during the initial 12 postoperative months. The study did not measure pain score, global assessment of treatment success or total adverse events. One study (265 participants; 303 THAs) evaluated the provision of hip precautions with versus without the prescription of postoperative equipment and restrictions to functional activities. Due to the quality of evidence being very low, we are uncertain if perceived satisfaction in the rate of recovery differed in people who were not prescribed postoperative equipment and restrictions (135/151 satisfied) compared to those prescribed equipment and restrictions (113/152) (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.93; 265 participants, one trial; number needed to treat for an additional beneficial outcome (NNTB) = 7). Due to the low quality evidence, we are uncertain if the incidence of hip dislocation differed between participants provided with hip precautions with (1/152) compared to without providing equipment or restrictions post-THA (0/151) (RR 2.98, 95% CI 0.12 to 72.59). The study did not measure pain, function, HRQOL, re-operation rates or total adverse events. One study (146 participants) investigated the provision of an enhanced postoperative education and rehabilitation service on hospital discharge to promote functional ADL versus a conventional rehabilitation intervention in the community. This study was of very low quality evidence. We were uncertain if the provision of enhanced postoperative education and rehabilitation improved function at six months follow-up, when assessed using the Objective and Subjective Functional Capability Index (146 participants, one trial; P > 0.05; no numerical results provided) compared to conventional rehabilitation. The study did not measure pain score, HRQOL, global assessment of treatment success, hip dislocation, re-operation rate or total adverse events. Very low quality evidence is available from single trials, thus we are uncertain if hip precautions with or without the addition of equipment and functional restrictions are effective in preventing dislocation and improving outcomes after THA. There is also insufficient evidence to support or refute the adoption of a postoperative community rehabilitation programme consisting of functional reintegration and education compared to conventional rehabilitation strategies based on functional outcomes. Further high-quality trials are warranted to assess the outcomes of different occupational therapy interventions both in the short and longer-term for those who undergo THA. An assessment of the impact of such interventions on pain and restriction on personal ADL, EADL and instrumental ADL is needed, and also of functional integration-type interventions rather than just hip precautions, equipment and restrictions.",
        "gold": "This Cochrane review is current to 29 April 2016. We searched the available evidence and included three studies, which had 492 people who had received a THA. Two of these studies investigated providing people with equipment, such as raised toilet seats and rails, and restricting their body movements (one of these studies also provided people with physiotherapy). One study investigated teaching participants about doing certain activities of daily living in a safe way to promote self-care without the risk of dislocating the new hip. The interventions were different and thus we did not combine the results. One study compared outcomes for participants randomised to the provision of hip precautions, equipment and functional restrictions versus no provision of hip precautions or equipment or functional restrictions. This is the main comparator in the review. Health-related quality of life (lower scores mean better quality of life) We cannot tell from our results whether the intervention has an important effect on health-related quality of life (no numerical results provided) because the sample size was small and the study design flawed. Function We cannot tell from our results whether the intervention has an important effect on functional outcomes (no numerical results provided) because the sample size was small and the study design flawed. Complications and adverse events There were no dislocations or adverse events. Outcomes of interest not measured Pain, treatment success and re-operation rate were not measured. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of the evidence. Due to issues relating to the small number of participants, size of studies and study conduct, including poorly blinding assessors to group allocation, we rated the quality of the evidence as 'very low'. Further research is highly likely to change the conclusions drawn from these results. We are uncertain whether the interventions improved outcomes."
    },
    {
        "index": "cochrane-simplification-test-373",
        "sentence": "Three randomised controlled trials were included. In two trials, there was a statistically significant reduction in the recurrence of painful periods in the LNG-IUD group compared with expectant management (RR 0.22, 95% CI 0.08 to 0.60, 95 women, I2 = 0%, moderate strength of evidence). The proportion of women who were satisfied with their treatment was also higher in the LNG-IUD group but did not reach statistical significance (RR 1.21, 95% CI 0.80 to 1.82, 95 women, I2 = 0%). The number of women reporting a change in menstruation was significantly higher in the LNG-IUD group (RR 37.80, 95% CI 5.40 to 264.60, 95 women, I2 = 0%) but the number of women not completing the allocated treatment did not differ between groups (RR 0.66, 95% CI 0.08 to 5.25, I2 = 43%). In one trial, women receiving LNG-IUD noted lower pain scores compared with women receiving gonadotrophin-releasing hormone agonists (MD -0.16, 95% CI -2.02 to 1.70, 40 women) but this did not reach statistical significance. There is limited but consistent evidence showing that postoperative LNG-IUD use reduces the recurrence of painful periods in women with endometriosis. Further well-designed RCTs are needed to confirm these findings.",
        "gold": "Endometriosis is the presence of endometrial tissue outside the uterus, usually in the pelvis, that can lead to infertility and pelvic pain. It is managed with surgery, hormonal medications, or a combination of both. The progestogen levonorgestrel is one such hormonal medication. The aim of this review was to assess whether the use of a hormone-releasing intrauterine device was beneficial for managing associated painful symptoms and for preventing recurrence of endometriosis following surgery. Although preliminary findings are encouraging, at this stage there is only limited evidence from three randomised trials of a beneficial role with the use of the LNG-IUD in reducing the recurrence of painful periods following surgery for endometriosis. The strength of the evidence was graded as moderate reflecting our belief that future evidence will most likely not change these findings."
    },
    {
        "index": "cochrane-simplification-test-374",
        "sentence": "We included 24 studies, with the majority (20/24) giving concerns about risk of bias. All of the included studies investigated food products; none investigated alcohol or tobacco. The majority were conducted in laboratory settings (14/24), with adult participants (17/24), and used between-participants designs (19/24). All studies were conducted in high-income countries, predominantly in the USA (14/24). Six studies investigated availability interventions, of which two changed the absolute number of different options available, and four altered the relative proportion of less-healthy (to healthier) options. Most studies (4/6) manipulated snack foods or drinks. For selection outcomes, meta-analysis of three comparisons from three studies (n = 154) found that exposure to fewer options resulted in a large reduction in selection of the targeted food(s): SMD \u22121.13 (95% confidence interval (CI) \u22121.90 to \u22120.37) (low certainty evidence). For consumption outcomes, meta-analysis of three comparisons from two studies (n = 150) found that exposure to fewer options resulted in a moderate reduction in consumption of those foods, but with considerable uncertainty: SMD \u22120.55 (95% CI \u22121.27 to 0.18) (low certainty evidence). Eighteen studies investigated proximity interventions. Most (14/18) changed the distance at which a snack food or drink was placed from the participants, whilst four studies changed the order of meal components encountered along a line. For selection outcomes, only one study with one comparison (n = 41) was identified, which found that food placed farther away resulted in a moderate reduction in its selection: SMD \u22120.65 (95% CI \u22121.29 to \u22120.01) (very low certainty evidence). For consumption outcomes, meta-analysis of 15 comparisons from 12 studies (n = 1098) found that exposure to food placed farther away resulted in a moderate reduction in its consumption: SMD \u22120.60 (95% CI \u22120.84 to \u22120.36) (low certainty evidence). Meta-regression analyses indicated that this effect was greater: the farther away the product was placed; when only the targeted product(s) was available; when participants were of low deprivation status; and when the study was at high risk of bias. The current evidence suggests that changing the number of available food options or altering the positioning of foods could contribute to meaningful changes in behaviour, justifying policy actions to promote such changes within food environments. However, the certainty of this evidence as assessed by GRADE is low or very low. To enable more certain and generalisable conclusions about these potentially important effects, further research is warranted in real-world settings, intervening across a wider range of foods - as well as alcohol and tobacco products - and over sustained time periods.",
        "gold": "Six studies involved availability interventions, of which four changed the relative proportion of less-healthy to healthier options, and two changed the absolute number of different options available. In statistical analyses that combined results from multiple studies, it was found that reducing the number of available options for a particular range or category of food(s) reduced selection of those food products (from analysing 154 participants) and possibly reduced consumption of those products (from 150 participants). However, the certainty of the evidence for these effects was low. Eighteen studies involved proximity interventions. Most (14/18) changed the distance at which a snack food or drink was placed from the participants, whilst four studies changed the order of meal components encountered along a line. One study found that this reduced selection of food (from analysing 41 participants), whilst in a statistical analysis combining results from multiple studies, it was found that placing food farther away reduced consumption of those food products (from analysing 1098 participants). However, the certainty of the evidence for these effects was very low and low, respectively. Key messages Mindful of its limitations, the current evidence suggests that changing the number of available food options or changing where foods are positioned could contribute to meaningful changes in behaviour, justifying policy actions to promote such changes to food environments. However, more high-quality studies in real-world settings are needed to make this finding more certain. How up-to-date is this review? The evidence is current to 23 July 2018."
    },
    {
        "index": "cochrane-simplification-test-375",
        "sentence": "Effect of PEP on HIV seroconversion  No randomized controlled trials were identified. Only one case-control study was included. HIV transmission was significantly associated with deep injury (OR 15, 95% CI 6.0 to 41), visible blood on the device (OR 6.2, 95% CI 2.2 to 21), procedures involving a needle placed in the source patient's blood vessel (OR 4.3, 95% CI 1.7 to 12), and terminal illness in the source patient (OR 5.6, 95% CI 2.0 to 16). After controlling for these risk factors, no differences were detected in the rates at which cases and controls were offered post-exposure prophylaxis with zidovudine. However, cases had significantly lower odds of having taken zidovudine after exposure compared to controls (OR 0.19, 95%CI 0.06 to 0.52). No studies were found that evaluated the effect of two or more antiretroviral drugs for occupational PEP. Adherence to and complications with PEP  Eight reports from observational comparative studies confirmed findings that adverse events were higher with a three-drug regimen, especially one containing indinavir. However, discontinuation rates were not significantly different. The use of occupational PEP is based on limited direct evidence of effect. However, it is highly unlikely that a definitive placebo-controlled trial will ever be conducted, and, therefore, on the basis of results from a single case-control study, a four-week regimen of PEP should be initiated as soon as possible after exposure, depending on the risk of seroconversion. There is no direct evidence to support the use of multi-drug antiretroviral regimens following occupational exposure to HIV. However, due to the success of combination therapies in treating HIV-infected individuals, a combination of antiretroviral drugs should be used for PEP. Healthcare workers should be counseled about expected adverse events and the strategies for managing these. They should also be advised that PEP is not 100% effective in preventing HIV seroconversion. A randomized controlled clinical trial is neither ethical nor practical. Due to the low risk of HIV seroconversion, a very large sample size would be required to have enough power to show an effect. More rigorous evaluation of adverse events, especially in the developing world, are required. Seeing that current practice is partly based on results from individual primary animal studies, we recommend a formal systematic review of all relevant animal studies.",
        "gold": "This review evaluated the effects of antiretroviral post-exposure prophylaxis (PEP) for preventing HIV infection following occupational exposure. No randomized controlled trials were identified. Only one case-control study provides evidence for using zidovudine monotherapy. The study found that, in the occupational setting, HIV transmission was significantly associated with deep injury, visible blood on the sharp instrument, procedures involving a needle placed in the source patient's blood vessel, and terminal illness in the source patient. After taking these into account, it was found that those who became infected with HIV had significantly lower odds of having taken zidovudine after exposure, compared to those who did not seroconvert. There is no direct evidence to support the use of multi-drug antiretroviral regimens following occupational exposure to HIV. However, due to the success of combination therapies in treating HIV-infected individuals, a combination of drugs should be used for PEP. Eight reports from other studies confirmed the findings that adverse events were higher with a three-drug regimen; however, discontinuation rates were not significantly different. A four-week regimen of post-exposure prophylaxis should be initiated as soon as possible after exposure, depending on the risk of seroconversion. Healthcare workers should be counseled about expected adverse events and given strategies for managing these events. They should also be advised that PEP is not 100% effective in preventing HIV seroconversion."
    },
    {
        "index": "cochrane-simplification-test-376",
        "sentence": "Overall there is an absence of evidence for behaviour therapy, except a small improvement in mood immediately following treatment when compared with an active control. CBT has small positive effects on disability and catastrophising, but not on pain or mood, when compared with active controls. CBT has small to moderate effects on pain, disability, mood and catastrophising immediately post-treatment when compared with treatment as usual/waiting list, but all except a small effect on mood had disappeared at follow-up. At present there are insufficient data on the quality or content of treatment to investigate their influence on outcome. The quality of the trial design has improved over time but the quality of treatments has not. Benefits of CBT emerged almost entirely from comparisons with treatment as usual/waiting list, not with active controls. CBT but not behaviour therapy has weak effects in improving pain, but only immediately post-treatment and when compared with treatment as usual/waiting list. CBT but not behaviour therapy has small effects on disability associated with chronic pain, with some maintenance at six months. CBT is effective in altering mood and catastrophising outcomes, when compared with treatment as usual/waiting list, with some evidence that this is maintained at six months. Behaviour therapy has no effects on mood, but showed an effect on catastrophising immediately post-treatment. CBT is a useful approach to the management of chronic pain. There is no need for more general RCTs reporting group means: rather, different types of studies and analyses are needed to identify which components of CBT work for which type of patient on which outcome/s, and to try to understand why.",
        "gold": "Our search found 42 trials of treatments which met our criteria, but only 35 provided data in a form that could be used. The two main types of psychological treatment are called cognitive behavioural therapy (CBT) and behaviour therapy. Both focus on helping people to change behaviour that maintains or worsens pain, disability, distress and catastrophic thinking; CBT also directly addresses the thoughts and feelings that are a problem for people with persistent pain. The effects of these two treatments on pain, disability, mood and catastrophic thinking were tested immediately after the treatment, and six months later. Small to moderate benefits, more for disability, mood and catastrophic thinking than for pain, were found in trials which compared CBT with no treatment. Some of these were still positive six months later. Behaviour therapy showed few and only brief benefits. Psychological therapies can help people with chronic pain reduce negative mood (depression and anxiety), disability, catastrophic thinking, and in some cases, pain. Although the overall effect is positive, we do not know enough about exactly which type of treatment is best for which person."
    },
    {
        "index": "cochrane-simplification-test-377",
        "sentence": "We reviewed a total of 881 full-text documents. From these, we identified 15 national initiatives, including more than 260,000 people, that met the inclusion criteria. None of the initiatives were provided in lower-middle-income or low-income countries. All initiatives except one used an uncontrolled pre-post study design. Because of high levels of study heterogeneity (I2 > 90%), we focused on individual initiatives rather than on pooled results. Ten initiatives provided sufficient data for quantitative analysis of impact (64,798 participants). As required by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) method, we graded the evidence as very low due to the risk of bias of the included studies, as well as variation in the direction and size of effect across the studies. Five of these showed mean decreases in average daily salt intake per person from pre-intervention to post-intervention, ranging from 1.15 grams/day less (Finland) to 0.35 grams/day less (Ireland). Two initiatives showed mean increase in salt intake from pre-intervention to post-intervention: Canada (1.66) and Switzerland (0.80 grams/day more per person); however in both countries the pre-intervention data point was from several years prior to the initiation of the intervention. The remaining initiatives did not show a statistically significant mean change. Seven of the 10 initiatives were multi-component and incorporated intervention activities of a structural nature (e.g. food product reformulation, food procurement policy in specific settings). Of those seven initiatives, four showed a statistically significant mean decrease in salt intake from pre-intervention to post-intervention, ranging from Finland to Ireland (see above), and one showed a statistically significant mean increase in salt intake from pre-intervention to post-intervention (Switzerland; see above). Nine initiatives permitted quantitative analysis of differential impact by sex (men and women separately). For women, three initiatives (China, Finland, France) showed a statistically significant mean decrease, four (Austria, Netherlands, Switzerland, United Kingdom) showed no significant change and two (Canada, United States) showed a statistically significant mean increase in salt intake from pre-intervention to post-intervention. For men, five initiatives (Austria, China, Finland, France, United Kingdom) showed a statistically significant mean decrease, three (Netherlands, Switzerland, United States) showed no significant change and one (Canada) showed a statistically significant mean increase in salt intake from pre-intervention to post-intervention. Information was insufficient to indicate whether a differential change in mean salt intake occurred from pre-intervention to post-intervention by other axes of equity included in the PROGRESS framework (e.g. education, place of residence). We identified no adverse effects of these initiatives. The number of initiatives was insufficient to permit other subgroup analyses, including stratification by intervention type, economic status of country and duration (or start year) of the initiative. Many studies had methodological strengths, including large, nationally representative samples of the population and rigorous measurement of dietary sodium intake. However, all studies were scored as having high risk of bias, reflecting the observational nature of the research and the use of an uncontrolled study design. The quality of evidence for the main outcome was low. We could perform a sensitivity analysis only for impact. Population-level interventions in government jurisdictions for dietary sodium reduction have the potential to result in population-wide reductions in salt intake from pre-intervention to post-intervention, particularly if they are multi-component (more than one intervention activity) and incorporate intervention activities of a structural nature (e.g. food product reformulation), and particularly amongst men. Heterogeneity across studies was significant, reflecting different contexts (population and setting) and initiative characteristics. Implementation of future initiatives should embed more effective means of evaluation to help us better understand the variation in the effects.",
        "gold": "We searched research papers and government reports and had direct communication with individuals working in salt reduction in their respective countries. The evidence is current as of 5 January 2015, when we last searched electronic databases. Initiatives in 15 countries met the inclusion criteria. Ten of these countries provided sufficient data for quantitative analysis, gathered from studies that included 64,798 participants. Initiatives ranged from one activity (e.g. in Japan, which at the time of writing had a public information campaign) to many activities (e.g. in the United Kingdom, which provided five activities including on-package nutrition information, restrictions on marketing to children and food product reformulation). Of the 15 countries that met inclusion criteria, seven provided information about funding source, of which six reported non-industry funding. The other eight countries did not report a funding source for one or more data point(s). Five of the 10 countries included in the quantitative analysis (China, Finland, France, Ireland and England) showed a decrease in salt intake after the intervention. Two of the 10 countries (Canada, Switzerland) showed an increase in salt intake after the intervention, however, in both countries the only data available were from several years prior to the intervention starting. Because the initiatives were very different, we cannot present an overall finding of whether these types of initiatives work. When we focused on the subset of seven countries whose salt reduction initiatives included multiple components and were not focused solely on educating the public, we found that more than half (four of seven) showed a decrease in salt intake from pre-intervention to post-intervention. When we examined the nine initiatives that analysed men and women separately, we found that amongst men, more than half (five of nine) showed a decrease in salt intake after the intervention. Amongst women, the pattern of findings was less clear, with three of nine interventions showing a decrease, two showing an increase and four showing no change in salt intake. Low-bias study designs, such as randomised controlled trials, typically are not suitable for evaluating complex initiatives such as these; therefore, we rated all of the studies included in this review as having low methodological quality. Large nationally representative samples of the population and careful measurement of dietary sodium intake were strengths of several studies. However, because of study design limitations, the trustworthiness of study results is not clear. Overall, our results show that national government initiatives have the potential to achieve population-wide reductions in salt intake, especially amongst men, and particularly if they employ more than one strategy and include structural activities such as food product reformulation (i.e. food companies putting less salt in food products). The wide variation of results across the studies we found presents a challenge in interpreting the current evidence and this warrants more research to help us understand this."
    },
    {
        "index": "cochrane-simplification-test-378",
        "sentence": "We identified 18 potentially relevant RCTs, but only seven met the inclusion criteria. All studies had a small number of participants, ranging from seven to 16 people per study and had a cross-over design. Three studies were of low risk of bias, while four were of uncertain risk. Amitriptyline (three studies), bromocriptine (one study), clonidine (one study), propranolol (one study), levodopa (Prolopa\u00ae) (one study) and tryptophan (one study) were compared with placebo. Studies evaluating bromocriptine, clonidine, propranolol and levodopa reported our primary outcome of indices of bruxism motor activity. Results were imprecise and consistent with benefit, no difference or harm. These were the specific findings for each of the drugs according to specific outcomes: 1. Amitriptyline versus placebo for masseteric electromyography (EMG) activity per minute: standardized mean difference (SMD) -0.28 (95% confidence interval (CI) -0.91 to 0.34; P value = 0.37), 2. bromocriptine versus placebo for bruxism episodes per hour: mean difference (MD) 0.60 (95% CI -2.93 to 4.13), bruxism bursts per hour: MD -2.00 (95% CI -53.47 to 49.47), bruxism bursts per episode: MD 0.50 (95% CI -1.85 to 2.85) or number of episodes with grinding noise: MD 2.40 (95% CI -24.00 to 28.80), 3. clonidine versus placebo for number of bruxism episodes per hour: MD -2.41 (95% CI -4.84 to 0.02), 4. propranolol versus placebo for the number of bruxism episodes per hour: MD 1.16 (95% CI -1.89 to 4.21), 5. L-tryptophan versus placebo for masseteric EMG activity per second: SMD 0.08 (95% CI -0.90 to 1.06) and 6. levodopa versus placebo for bruxism episodes per hour of sleep: MD -1.47 (95% CI -3.64 to 0.70), for bruxism bursts per episode: MD 0.06 (95% CI -2.47 to 2.59). We combined several secondary outcomes (sleep duration, masseteric EMG activity per minute and pain intensity) in a meta-analysis for comparison of amitriptyline with placebo. The results for most comparisons were uncertain because of statistical imprecision. One study reported that clonidine reduced rapid eye movement (REM) sleep stage and increased the second stage of sleep. However, results for other sleep-related outcomes with clonidine were uncertain. Adverse effects were frequent in people who took amitriptyline (5/10 had drowsiness, difficulty awakening in the morning, insomnia or xerostomia compared with 0/10 in the placebo group), as well as in people who received propranolol (7/16 had moderate-to-severe xerostomia compare with 2/16 in the placebo group). Clonidine was associated with prolonged morning hypotension in three of 16 participants. The use of preventive medication avoided any adverse effects in people treated with levodopa and bromocriptine. There was insufficient evidence on the effectiveness of pharmacotherapy for the treatment of sleep bruxism. This systematic review points to the need for more, well-designed, RCTs with larger sample sizes and adequate methods of allocation, outcome assessment and duration of follow-up. Ideally, parallel RCTs should be used in future studies to avoid the bias associated with cross-over studies. There is a need to standardize the outcomes of RCTs on treatments for sleep bruxism.",
        "gold": "We searched scientific databases for clinical trials comparing any drug with placebo (a dummy treatment), other drugs or no treatment in people of any age with sleep bruxism. The evidence is current to August 2014. A total of 18 studies were identified and seven were included in the review. Each individual study involved a very small number of participants (7-16) and four of them were of moderate methodological quality. Amitriptyline (three studies), bromocriptine (one study), clonidine (one study), propranolol (one study), levodopa (Prolopa\u00ae) (one study) and tryptophan (one study) were compared with placebo. Amitriptyline and L-tryptophan did not reduce activity of the jaw muscles, measured using electromyography. Bromocriptine,clonidine, propanolol and levodopa did not significantly reduce the number of bruxism episodes per hour when compared to placebo. This systematic review concluded that there is not enough evidence in the literature to show that drugs can reduce sleep bruxism."
    },
    {
        "index": "cochrane-simplification-test-379",
        "sentence": "We identified 10 randomized controlled trials with 1015 participants. All studies compared an enteral formula or additional supplemental omega-3 fatty acids (i.e. eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)), gamma-linolenic acid (GLA), and antioxidants. We assessed some of the included studies as having high risk of bias due to methodological shortcomings. Studies were heterogenous in nature and varied in several ways, including type and duration of interventions given, calorific targets, and reported outcomes. All studies reported mortality. For the primary outcome, study authors reported no differences in all-cause mortality (longest period reported) with the use of an immunonutrition enteral formula or additional supplements of omega-3 fatty acids and antioxidants (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07; participants = 1015; studies = 10; low-quality evidence). For secondary outcomes, we are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants reduces ICU length of stay (mean difference (MD) -3.09 days. 95% CI -5.19 to -0.99; participants = 639; studies = 8; very low-quality evidence) and ventilator days (MD -2.24 days, 95% CI -3.77 to -0.71; participants = 581; studies = 7; very low-quality evidence). We are also uncertain whether omega-3 fatty acids and antioxidants improve oxygenation, defined as ratio of partial pressure of arterial oxygen (PaO\u2082) to fraction of inspired oxygen (FiO\u2082), at day 4 (MD 39 mmHg, 95% CI 10.75 to 67.02; participants = 676; studies = 8), or whether they increase adverse events such as cardiac events (RR 0.87, 95% CI 0.09 to 8.46; participants = 339; studies = 3; very low-quality evidence), gastrointestinal events (RR 1.11, 95% CI 0.71 to 1.75; participants = 427; studies = 4; very low-quality evidence), or total adverse events (RR 0.91, 95% CI 0.67 to 1.23; participants = 517; studies = 5; very low-quality evidence). This meta-analysis of 10 studies of varying quality examined effects of omega-3 fatty acids and/or antioxidants in adults with ARDS. This intervention may produce little or no difference in all-cause mortality between groups. We are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves the duration of ventilator days and ICU length of stay or oxygenation at day 4 due to the very low quality of evidence. Adverse events associated with immunonutrition are also uncertain, as confidence intervals include the potential for increased cardiac, gastrointestinal, and total adverse events.",
        "gold": "The evidence is current up to April 2018. We included in this review 10 studies with 1015 adult participants. These studies were conducted in intensive care units and compared standard nutrition (the usual nutrition given to patients with ARDS) versus nutrition supplemented with omega-3 fatty acids or placebo (a substance with no active effect), and compared either with or without antioxidants. Antioxidants are molecules that can inhibit or slow down oxidation - a reaction that can cause inflammation and damage cells. It is unclear whether use of omega-3 fatty acids and antioxidants as part of nutritional intake in patients with ARDS improves long-term survival. It is uncertain whether omega-3 fatty acids and antioxidants reduce length of ICU stay and the number of days spent on a ventilator, or if they improve oxygenation. It is also unclear if this type of nutrition causes increased harm. Findings of this review are limited by lack of standardization among the included studies in terms of methods, types of nutritional supplements given, and reporting of outcome measures. We rated the quality of evidence as low to very low."
    },
    {
        "index": "cochrane-simplification-test-380",
        "sentence": "The 33 eligible studies largely compared open questions with checklist-type questions or rating scales. Two included participant interviews. Despite different designs, populations and details of questioning methods, the narrative review showed that more specific questioning of participants led to more AEs detected compared to a more general enquiry. A subset of six studies suggested that more severe, bothersome, or otherwise clinically relevant AEs were reported when an initial open enquiry was used, while some less severe, bothersome, or clinically relevant AEs were only reported with a subsequent specific enquiry. However, two studies showed that quite severe or debilitating AEs were only detected by an interview, while other studies did not find a difference in the nature of AEs between elicitation methods. No conclusions could be made regarding the impact of question method on the ability to detect a statistically significant difference between study groups. There was no common statistical rubric, but we were able to represent some effect measures as a risk ratio of the proportion of participants with at least one AE. This showed a lower level of reporting for open questions (O) compared to checklists (CL), with a range for the risk ratios of 0.12 to 0.64. This review supports concerns that methods to elicit participant-reported AEs influence the detection of these data. There was a risk for under-detection of AEs in studies using a more general elicitation method compared to those using a comprehensive method. These AEs may be important from a clinical perspective or for patients. This under-detection could compromise ability to pool AE data. However, the impact on the nature of the AE detected by different methods is unclear. The wide variety and low quality of methods to compare elicitation strategies limited this review. Future studies would be improved by using and reporting clear definitions and terminology for AEs (and other important variables), frequency and time period over which they were ascertained, how they were graded, assessed for a relationship to the study drug, coded, and tabulated/reported. While the many potential AE endpoints in a trial may preclude the development of general AE patient-reported outcome measurement instruments, much could also be learnt from how these employ both quantitative and qualitative methods to better understand data elicited. Any chosen questioning method needs to be feasible for use by both staff and participants.",
        "gold": "Clinical drug trials or studies are usually conducted to assess how well the drug works but also whether it causes any harm (side effects or adverse effects). Adverse effects can be detected by the trial doctor examining participants or taking some blood samples or doing other kinds of tests. The trial staff can also ask participants about how they are feeling after taking the trial drug. However, the way participants are asked about their health can vary from trial to trial, or even within a trial. In some trials, participants may be asked a simple open question such as 'how have you been feeling?', while in other trials, participants may be asked about whether they have had any of a long list of possible symptoms (such as 'have you had a headache, stomach ache, or sore muscles?'). There has been concern that these different kinds of questions and how they are phrased will impact on what participants report about their health during a trial. This might then affect the trial's results and what we know about the side effects of drugs. We did this review to look at studies that compared different types of participant questioning methods in order to investigate these issues. We found 33 studies comparing mainly open questions with checklist-type questions, but also some ratings scales and participant interviews. While the studies were all very different in terms of the types of disease, drugs, and patients studied, we found in general that, as would be expected, when a more specific type of question was asked (like a checklist), participants reported more symptoms. What is interesting is that, in those studies that looked more closely at the types of symptoms reported, it seems that an open question picks up the more severe or bothersome symptoms compared to a checklist-type question. However, some studies found that even quite severe or bothersome symptoms were not reported when a participant is asked an open question and these severe symptoms will only be reported with the more specific question. This makes it difficult to say whether one method is better than any other and the different questioning methods may, in fact, be complementary and therefore should be used together. It is also difficult to say what a specific question should include, as it might take too long for a participant to have to answer a very long list. While more research is needed to resolve the remaining uncertainties, it is very important for trials to be clear about which kind of questioning was used when they publish their results. This will help readers understand the trial's findings about the side effects and make it easier to make accurate comparisons between trials."
    },
    {
        "index": "cochrane-simplification-test-381",
        "sentence": "We identified 582 records from the databases and search strategies. We found 10 further records by searching other resources (handsearching). We removed 211 duplicate records and screened 381 records (title and abstract) for inclusion in the review. We excluded 364 records based on the title and abstract and assessed 17 full-text articles. We excluded 15 studies: eight studies did not assess interventions to prevent SUDEP; five studies measured sensitivity of devices to detect GTCS but did not directly measure SUDEP; and two studies assessed risk factors for SUDEP but not interventions for preventing SUDEP. One listed study is awaiting classification. We included one case-control study at serious risk of bias within a qualitative analysis in this review. This study of 154 cases of SUDEP and 616 controls ascertained a protective effect for the presence of nocturnal supervision (unadjusted odds ratio (OR) 0.34, 95% confidence interval (CI) 0.22 to 0.53) and when a supervising person shared the same bedroom or when special precautions, for example a listening device, were used (unadjusted OR 0.41, 95% CI 0.20 to 0.82). This effect was independent of seizure control. Non-SUDEP deaths; changes to anxiety, depression, and quality of life; and number of hospital attendances were not reported. We found very low-quality evidence of a preventative effect for nocturnal supervision against SUDEP. Further research is required to identify the effectiveness of other current interventions, for example seizure detection devices, safety pillows, SSRIs, early surgical evaluation, educational programmes, and opiate and adenosine antagonists in preventing SUDEP in people with epilepsy.",
        "gold": "We judged the quality of the evidence from this review to be very low as the only included study was not randomised, and information about supervision measures to prevent SUDEP was not available for 40% of the people with epilepsy who did not experience SUDEP. We found very limited, low-quality evidence that supervision at night prevents SUDEP. Further research is needed to identify if other treatments, such as seizure detection devices, safety pillows, and drug interventions working on serotonin, adenosine, and opiate levels in the brain are effective in preventing SUDEP in people with epilepsy."
    },
    {
        "index": "cochrane-simplification-test-382",
        "sentence": "Searches retrieved 35 references to 21 individual studies, of which seven (n = 208) were eligible for inclusion. One study was of parallel design with the remaining six being cross-over in design; participant numbers ranged from 17 to 75. The total study duration varied between four days and two years. The age of participants ranged between seven and 63 years with a wide range of disease severity reported. Six studies enrolled participants who were clinically stable, whilst participants in one study had been hospitalised with an infective exacerbation. All studies compared autogenic drainage to one (or more) other recognised airway clearance technique. Exercise is commonly used as an alternative therapy by people with cystic fibrosis; however, there were no studies identified comparing exercise with autogenic drainage. The quality of the evidence was generally low or very low. The main reasons for downgrading the level of evidence were the frequent use of a cross-over design, outcome reporting bias and the inability to blind participants. The review's primary outcome, forced expiratory volume in one second, was the most common outcome measured and was reported by all seven studies; only three studies reported on quality of life (also a primary outcome of the review). One study reported on adverse events and described a decrease in oxygen saturation levels whilst performing active cycle of breathing techniques, but not with autogenic drainage. Six of the seven included studies measured forced vital capacity and three of the studies used mid peak expiratory flow (per cent predicted) as an outcome. Six studies reported sputum weight. Less commonly used outcomes included oxygen saturation levels, personal preference, hospital admissions or intravenous antibiotics. There were no statistically significant differences found between any of the techniques used with respect to the outcomes measured except when autogenic drainage was described as being the preferred technique of the participants in one study over postural drainage and percussion. Autogenic drainage is a challenging technique that requires commitment from the individual. As such, this intervention merits systematic review to ensure its effectiveness for people with cystic fibrosis. From the studies assessed, autogenic drainage was not found to be superior to any other form of airway clearance technique. Larger studies are required to better evaluate autogenic drainage in comparison to other airway clearance techniques in view of the relatively small number of participants in this review and the complex study designs. The studies recruited a range of participants and were not powered to assess non-inferiority. The varied length and design of the studies made the analysis of pooled data challenging.",
        "gold": "We searched the literature for studies comparing at least two sessions of autogenic drainage with other breathing techniques and devices which help to clear the lungs of mucus. We included seven studies in the review involving 208 people with cystic fibrosis, aged between seven and 63 years of age. People were selected for one physiotherapy treatment or the other randomly. The number of people in the studies ranged from 17 to 75, and had a wide range of disease severity. The studies lasted from four days to two years in total. We did not find any clear evidence that autogenic drainage was better than the other techniques for lung function or quality of life in either the short-term or long-term studies. This was also true for our other outcome measures such as hospital admissions, additional antibiotic treatment, exercise tolerance and oxygen saturation, but in one study autogenic drainage was the preferred technique compared to postural drainage and percussion. Exercise was identified as a comparator for airway clearance by the authors of this review but no included studies used it in this way, even though it is often used as an alternative therapy by people with cystic fibrosis. Overall, the quality of the evidence from the studies was judged to be mainly low or very low. The main problems for this being the small numbers of participants in each study, the unclear reporting of results in the studies and the study design used. In one study, which was classed as having a high risk of bias due to incomplete results, those taking part had to change physiotherapy technique halfway through the study and there were many who dropped out and did not comply with the postural drainage and percussion treatment arm. Five of the seven studies used research staff to assess results who did not know which technique each person was using and this improved the quality of the evidence and reduced any bias."
    },
    {
        "index": "cochrane-simplification-test-383",
        "sentence": "Twenty five studies (1305 participants) were included in the review, of which 22 studies (1060 participants) contributed data to meta-analyses. Based on thirteen studies, psychological therapies, all using a CBT approach, were more effective than TAU/WL in achieving clinical response at post-treatment (RR 0.64, 95%CI 0.55 to 0.74), and also in reducing anxiety, worry and depression symptoms. No studies conducted longer-term assessments of CBT against TAU/WL. Six studies compared CBT against supportive therapy (non-directive therapy and attention-placebo conditions). No significant difference in clinical response was indicated between CBT and supportive therapy at post-treatment (RR 0.86, 95%CI 0.70 to 1.06), however, significant heterogeneity was indicated, which was partly explained by the number of therapy sessions. Psychological therapy based on CBT principles is effective in reducing anxiety symptoms for short-term treatment of GAD. The body of evidence comparing CBT with other psychological therapies is small and heterogeneous, which precludes drawing conclusions about which psychological therapy is more effective. Further studies examining non-CBT models are required to inform health care policy on the most appropriate forms of psychological therapy in treating GAD.",
        "gold": "This review aimed to find out whether psychological therapies are effective for GAD, and whether cognitive behavioural therapy (CBT) is more effective than other psychological therapy approaches, including psychodynamic and supportive therapies. The review included 25 studies, with a total of 1305 participants. All the studies used a CBT approach, and compared CBT against treatment as usual or waiting list (13 studies), or against another psychological therapy (12 studies). The review showed that people attending for psychological therapy based on a CBT approach were more likely to have reduced anxiety at the end of treatment than people who received treatment as usual or were on a waiting list for therapy. CBT was also very effective in reducing secondary symptoms of worry and depression. People who attended for group CBT and older people were more likely to drop out of therapy. None of the studies comparing CBT with treatment as usual or waiting list looked at the long-term effectiveness of CBT. It is not clear whether people attending for CBT sessions were more likely to have reduced anxiety than people attending for psychodynamic therapy or supportive therapy, because only one study compared CBT with psychodynamic therapy, and the six studies that compared CBT with supportive therapy showed differing results. None of the studies included in the review reported on the possible side effects or acceptability of psychological therapies. More studies should be carried out to establish whether psychodynamic and supportive therapies are effective for GAD, and whether CBT is more helpful than other psychological therapy approaches in treating GAD."
    },
    {
        "index": "cochrane-simplification-test-384",
        "sentence": "Twelve trials (1,856 women) met the inclusion criteria. Eight of the included trials compared treatment with placebo and the remaining four trials compared progestogen administration with no treatment. The trials were a mix of multicenter and single-center trials, conducted in India, Jordan, UK and USA. In five trials women had had three or more consecutive miscarriages and in seven trials women had suffered two or more consecutive miscarriages. Routes, dosage and duration of progestogen treatment varied across the trials. The majority of trials were at low risk of bias for most domains. Ten trials (1684 women) contributed data to the analyses. The meta-analysis of all women, suggests that there may be a reduction in the number of miscarriages for women given progestogen supplementation compared to placebo/controls (average risk ratio (RR) 0.73, 95% confidence interval (CI) 0.54 to 1.00, 10 trials, 1684 women, moderate-quality evidence). A subgroup analysis comparing placebo-controlled versus non-placebo-controlled trials, trials of women with three or more prior miscarriages compared to women with two or more miscarriages and different routes of administration showed no clear differences between subgroups for miscarriage. None of the trials reported on any secondary maternal outcomes, including severity of morning sickness, thromboembolic events, depression, admission to a special care unit, or subsequent fertility. There was probably a slight benefit for women receiving progestogen seen in the outcome of live birth rate (RR 1.07, 95% CI 1.00 to 1.13, 6 trials, 1411 women, moderate-quality evidence). We are uncertain about the effect on the rate of preterm birth because the evidence is very low-quality (RR 1.13, 95% CI 0.53 to 2.41, 4 trials, 256 women, very low-quality evidence). No clear differences were seen for women receiving progestogen for the other secondary outcomes including neonatal death, fetal genital abnormalities or stillbirth. There may be little or no difference in the rate of low birthweight and trials did not report on the secondary child outcomes of teratogenic effects or admission to a special care unit. For women with unexplained recurrent miscarriages, supplementation with progestogen therapy may reduce the rate of miscarriage in subsequent pregnancies.",
        "gold": "We searched for evidence on 6 July 2017 and identified a total of 13 trials that enrolled a total of 2556 women with a history of recurrent miscarriages. These trials found that giving progestogen medication to women with recurrent miscarriages early in their pregnancy may help lower the rates of miscarriage in that pregnancy from 27.5% to 20.1%. We believe that these findings are based on evidence of only moderate quality, so we cannot be certain about the results. We did not find that giving the progestogen medication by mouth, as a shot (injection), or in the vagina, was any better than any of the other ways. We also found that the trials showed that giving progestogen to women with prior recurrent miscarriages made the chances of having a live baby in the current pregnancy slightly higher. We are uncertain about the effect on the rate of preterm birth because the evidence is very low-quality. We did not find evidence of improvement in other outcomes such as newborn death, stillbirth, low birthweight, or newborn birth defects for women given progestogens. We found evidence from randomized controlled trials that giving progestogen medication may prevent miscarriage for women with recurrent previous miscarriages."
    },
    {
        "index": "cochrane-simplification-test-385",
        "sentence": "In total, we included 14 studies with 1298 participants: nine studies (704 participants) compared CM vs. control, and five studies (594 participants) compared MIB interventions vs. control. We did not find any studies that assessed other types of psychosocial interventions. For the most part, it was unclear if included studies adequately controlled for biases within their studies as such information was not often reported. We assessed risk of bias in the included studies relating to participant selection, allocation concealment, personnel and outcome assessor blinding, and attrition. The included trials rarely captured maternal and neonatal outcomes. For studies that did measure such outcomes, no difference was observed in pre-term birth rates (RR 0.71, 95% confidence interval (CI) 0.34 to 1.51; three trials, 264 participants, moderate quality evidence), maternal toxicity at delivery (RR 1.18, 95% CI 0.52 to 2.65; two trials, 217 participants, moderate quality evidence), or low birth weight (RR 0.72, 95% CI 0.36 to 1.43; one trial, 160 participants, moderate quality evidence). However, the results did show that neonates remained in hospital for fewer days after delivery in CM intervention groups (RR -1.27, 95% CI -2.52 to -0.03; two trials, 103 participants, moderate quality evidence). There were no differences observed at the end of studies in retention or abstinence (as assessed by positive drug test at the end of treatment) in any psychosocial intervention group compared to control (Retention: RR 0.99, 95% CI 0.93 to 1.06, nine trials, 743 participants, low quality evidence; and Abstinence: RR 1.14, 95% CI 0.75 to 1.73, three trials, 367 participants, low quality evidence). These results held for both CM and MIB combined. Overall, the quality of the evidence was low to moderate. The present evidence suggests that there is no difference in treatment outcomes to address drug use in pregnant women with use of psychosocial interventions, when taken in the presence of other comprehensive care options. However, few studies evaluated obstetrical or neonatal outcomes and rarely did so in a systematic way, making it difficult to assess the effect of psychosocial interventions on these clinically important outcomes. It is important to develop a better evidence base to evaluate psychosocial modalities of treatment in this important population.",
        "gold": "Researchers from the Cochrane Collaboration examined the evidence published up to January 2015 and included 14 studies with 1298 pregnant women in this Cochrane review. The 1298 pregnant women received either CM or MIB techniques in adjunct to other comprehensive care options; women in the control group received usual care that included pharmacological treatment such as methadone maintenance, counselling, prenatal care, STD counselling and testing, transportation, and/or childcare. Nine studies used CM techniques vs. usual care, while five studies involved MIB techniques vs. usual care. All of the studies were completed in the United States of America and most participants were African American. Most studies used the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-R) criteria to determine drug dependence. There were no differences in retention or abstinence between CM or MIB techniques and usual care. There were also no differences in birth outcomes between the groups. Overall, there is low to moderate quality of evidence from the included studies. Allocation methods were often described in very limited manner. Furthermore, many studies lacked attrition information which could have impacted results. While further information related to these methods could be helpful, future randomized trials using psychosocial interventions are unlikely to show a benefit. In addition, there was significant heterogeneity in terms of methods for measuring outcomes."
    },
    {
        "index": "cochrane-simplification-test-386",
        "sentence": "We identified 31 studies (44 reports) including 27,071 participants and two ongoing studies. The risk of bias in the studies was low or unclear for several domains. Compared to the transfemoral approach, the transradial approach reduced short-term net adverse clinical events (NACE) (i.e. assessed during hospitalisation and up to 30 days of follow-up) (RR 0.76, 95% CI 0.61 to 0.94; 17,133 participants; 4 studies; moderate quality evidence), cardiac death (RR 0.69, 95% CI 0.54 to 0.88; 11,170 participants; 11 studies; moderate quality evidence). However, short-term myocardial infarction was similar between both groups (RR 0.91, 95% CI 0.81 to 1.02; 19,430 participants; 11 studies; high quality evidence). The transradial approach had a lower procedural success rate (RR 0.97, 95% CI 0.96 to 0.98; 25,920 participants; 28 studies; moderate quality evidence), but was associated with a lower risk of all-cause mortality (RR 0.77, 95% CI 0.62 to 0.95; 18,955 participants; 10 studies; high quality evidence), bleeding (RR 0.54, 95% CI 0.40 to 0.74; 23,043 participants; 20 studies; low quality evidence), and access site complications (RR 0.36, 95% CI 0.22 to 0.59; 16,112 participants; 24 studies; low quality evidence). Transradial approach for diagnostic CA or PCI (or both) in CAD may reduce short-term NACE, cardiac death, all-cause mortality, bleeding, and access site complications. There is insufficient evidence regarding the long-term clinical outcomes (i.e. beyond 30 days of follow-up).",
        "gold": "Our search yielded 31 eligible studies comparing the transradial approach to the transfemoral approach in people undergoing diagnostic or therapeutic (or both) coronary catheterisation procedures in different settings, whether urgent (during heart attacks (myocardial infarctions)) or elective (planned procedure). The trials were carried out in many countries and regions, including Canada, China, Europe, Japan, and USA. We also identified two ongoing studies. The evidence was current to October 2017. Transradial access was associated with a reduction in the composite outcome (comprising two or more combined outcomes) of net adverse clinical events (NACE), including death from cardiac causes, myocardial infarction (injury of the heart muscle), stroke (insult to the brain), need to reintervene on the same site of coronary artery stenosis (narrowing), and bleeding during the first 30 days following intervention. When assessing individual outcomes, the risk of myocardial infarction and stroke was similar between groups. Transradial access reduced death from cardiac causes, death from all causes during the first 30 days following intervention, bleeding, and local complications at the access site. The transradial approach shortened the length of stay in hospital, but was associated with a higher radiation exposure and more technical failures requiring an alternate vascular access route. We rated the quality of the evidence for short-term myocardial infarction and all-cause death as high. We rated short-term NACE, cardiac death, and success of the procedure as moderate quality evidence. Evidence for bleeding and access site complications was low quality."
    },
    {
        "index": "cochrane-simplification-test-387",
        "sentence": "We identified two studies of palliative care interventions for people with advanced dementia. We did not pool data due to the heterogeneity between the two trials in terms of the interventions and the settings. The two studies measured 31 different outcomes, yet they did not measure the same outcome. There are six ongoing studies that we expect to include in future versions of this review. Both studies were at high risk of bias, in part because blinding was not possible. This and small sample sizes meant that the overall certainty of all the evidence was very low. One individually randomised RCT (99 participants) evaluated the effect of a palliative care team for people with advanced dementia hospitalised for an acute illness. While this trial reported that a palliative care plan was more likely to be developed for participants in the intervention group (risk ratio (RR) 5.84, 95% confidence interval (CI) 1.37 to 25.02), the plan was only adopted for two participants, both in the intervention group, while in hospital. The palliative care plan was more likely to be available on discharge in the intervention group (RR 4.50, 95% CI 1.03 to 19.75). We found no evidence that the intervention affected mortality in hospital (RR 1.06, 95% CI 0.53 to 2.13), decisions to forgo cardiopulmonary resuscitation in hospital or the clinical care provided during hospital admission, but for the latter, event rates were low and the results were associated with a lot of uncertainty. One cluster RCT (256 participants, each enrolled with a family carer) evaluated the effect of a decision aid on end-of-life feeding options on surrogate decision-makers of nursing home residents with advanced dementia. Data for 90 participants (35% of the original study) met the definition of advanced dementia for this review and were re-analysed for the purposes of the review. In this subset, intervention surrogates had lower scores for decisional conflict measured on the Decisional Conflict Scale (mean difference -0.30, 95% CI -0.61 to 0.01, reduction of 0.3 to 0.4 units considered meaningful) and were more likely than participants in the control group to discuss feeding options with a clinician (RR 1.57, 95% CI 0.93 to 2.64), but imprecision meant that there was significant uncertainty about both results. Very little high quality work has been completed exploring palliative care interventions in advanced dementia. There were only two included studies in this review, with variation in the interventions and in the settings that made it impossible to conduct a meta-analysis of data for any outcome. Thus, we conclude that there is insufficient evidence to assess the effect of palliative care interventions in advanced dementia. The fact that there are six ongoing studies at the time of this review indicates an increased interest in this area by researchers, which is welcome and needed.",
        "gold": "We examined the research published up to January 2016. We found only two suitable studies (189 people), both from the US. We also found six studies that were underway but the results were not yet published. One study found that having a small team of doctors and nurses trained in palliative care made little difference to how people with advanced dementia were treated while in hospital. But, having this special team meant that more people had a palliative care plan when they were discharged from hospital. The other study measured if giving written information to relatives explaining the different methods that can be used to feed people with advanced dementia helped either the relatives or the person. This study found that giving relatives this information made it a little easier for relatives to make decisions about what methods would be used to feed the person with dementia. We only found two studies and the two palliative care methods in these studies were very different. We cannot be very certain about how accurate either of these results reported here are, partly because only a small number of people took part in the studies. So from these studies, it is hard to be sure whether palliative care makes a difference to people with advanced dementia. Little research has been done about people with advanced dementia, often because of ethical concerns. However, although it is hard to do research with people with dementia, more well-designed studies are required to work out how palliative care can be used best in this special population."
    },
    {
        "index": "cochrane-simplification-test-388",
        "sentence": "Three trials reporting two different sequencing comparisons were identified. There were no significant differences between the various methods of sequencing adjuvant therapy for local recurrence-free survival, overall survival, relapse-free survival and metastasis-free survival based on 1166 randomised women in three trials. Concurrent chemoradiation increased anaemia (OR 1.54; 95% confidence interval (CI) 1.10 to 2.15), telangiectasia (OR 3.85; 95% CI 1.37 to 10.87) and pigmentation (OR 15.96; 95% CI 2.06 to 123.68). Treated women did not report worse cosmesis with concurrent chemoradiation but physician-reported assessments did (OR 1.14; 95% CI 0.42 to 3.07). Other measures of toxicity did not differ between the two types of sequencing. On the basis of one trial (244 women), RT before CT was associated with an increased risk of neutropenic sepsis (OR 2.96; 95% CI 1.26 to 6.98) compared with CT before RT, but other measures of toxicity did not differ. The data included in this review, from three well-conducted randomised trials, suggest that different methods of sequencing CT and RT do not appear to have a major effect on recurrence or survival for women with breast cancer if RT is commenced within seven months after surgery.",
        "gold": "This review examined the current evidence on the best way to administer chemotherapy and radiotherapy following breast-conserving surgery. We were able to include three randomised trials. Two of these, with 853 women, assessed radiotherapy and chemotherapy given at the same time versus chemotherapy given first followed by radiotherapy. The third trial randomised 244 women to radiotherapy followed by chemotherapy versus chemotherapy followed by radiotherapy. The evidence produced by these three well-conducted trials suggests that recurrence of a woman's cancer and her chances of dying from breast cancer are similar regardless of the order of the treatments, provided that both radiotherapy and chemotherapy are commenced within seven months of the surgery. The trials provided limited information regarding adverse events, side effects or quality of life associated with the different sequences of treatment. The limited evidence available does suggest that the frequency and severity of side effects of chemotherapy and radiotherapy are similar regardless of which sequence is used. However, it should be noted that the women in these trials were treated, on average, in the early 2000s. As a result, the trials do not assess the modern types of radiotherapy, and new types of chemotherapy (such as taxanes) or other drugs (such as Herceptin). We will add relevant trials that include these more recent treatments to future updates of this review."
    },
    {
        "index": "cochrane-simplification-test-389",
        "sentence": "We evaluated nine RCTs involving a total of 622 participants. The RCTs were conducted in the community setting, with interventions mainly delivered by health professionals, and had a short- to medium-term follow up (up to 24 weeks). Three RCTs compared CrP plus resistance or weight training with placebo plus resistance or weight training, the other RCTs compared CrP alone versus placebo. We focused this review on investigating which dose of CrP would prove most effective versus placebo and therefore assessed the results according to CrP dose. However, in order to find out if CrP works in general, we also analysed the effect of all pooled CrP doses versus placebo on body weight only. Across all CrP doses investigated (200 \u00b5g, 400 \u00b5g, 500 \u00b5g, 1000 \u00b5g) we noted an effect on body weight in favour of CrP of debatable clinical relevance after 12 to 16 weeks of treatment: mean difference (MD) -1.1 kg (95% CI -1.7 to -0.4); P = 0.001; 392 participants; 6 trials; low-quality evidence (GRADE)). No firm evidence and no dose gradient could be established when comparing different doses of CrP with placebo for various weight loss measures (body weight, body mass index, percentage body fat composition, change in waist circumference). Only three studies provided information on adverse events (low-quality evidence (GRADE)). There were two serious adverse events and study dropouts in participants taking 1000 \u00b5g CrP, and one serious adverse event in an individual taking 400 \u00b5g CrP. Two participants receiving placebo discontinued due to adverse events; one event was reported as serious. No study reported on all-cause mortality, morbidity, health-related quality of life or socioeconomic effects. We found no current, reliable evidence to inform firm decisions about the efficacy and safety of CrP supplements in overweight or obese adults.",
        "gold": "We included nine randomised controlled trials which compared the efficacy and safety of 8 to 24 weeks of chromium supplementation and placebo in overweight or obese adults (i.e. with a body mass index between 25 and 29.9 kg/m2 defining being overweight and a body mass index of 30kg/m2 or more defining obesity). A total of 622 participants took part in the studies, 346 participants received chromium picolinate and 276 received placebo. The evidence is current to December 2012. When the results obtained from the doses of chromium picolinate investigated (200 \u00b5g, 400 \u00b5g, 500 \u00b5g, 1000 \u00b5g) were pooled, study participants lost around 1 kg of body weight more than participants receiving placebo. We were unable to find good evidence that this potential weight loss effect increased with increasing dose of chromium picolinate. Only three of nine studies provided information on adverse events, so we were unable to determine whether chromium picolinate supplements are safe and whether any potential harms may increase with dose. In addition, the length of studies included was rather short (maximum of 24 weeks), so we were unable to determine any long-term effects of supplementation. No study reported whether supplementation was associated with increases in deaths from any cause or illnesses (such as myocardial infarction or stroke), or the health-related quality of life or socioeconomic effects of supplementation. The overall quality of evidence was considered low and we have inadequate information from which to draw conclusions about the efficacy and safety of chromium picolinate supplementation in overweight or obese adults."
    },
    {
        "index": "cochrane-simplification-test-390",
        "sentence": "Eleven studies with a total of 886 participants were included in the review. These evaluated a range of comparisons in a range of surgical wounds healing by secondary intention. In general studies were small and some did not present data or analyses that could be easily interpreted or related to clinical outcomes. These factors reduced the quality of the evidence. Two comparisons compared different iodine preparations with no antiseptic treatment and found no clear evidence of effects for these treatments. The outcome data available were limited and what evidence there was low quality. One study compared a zinc oxide mesh dressing with a plain mesh dressing. There was no clear evidence of a difference in time to wound healing between groups. There was some evidence of a difference in measures used to assess wound infection (wound with foul smell and number of participants prescribed antibiotics) which favoured the zinc oxide group. This was low quality evidence. One study reported that sucralfate cream increased the likelihood of healing open wounds following haemorrhoidectomy compared to a petrolatum cream (RR: 1.50, 95% CI 1.13 to 1.99) over a three week period. This evidence was graded as being of moderate quality. The study also reported lower wound pain scores in the sucralfate group. There was a reduction in time to healing of open wounds following haemorrhoidectomy when treated with Triclosan post-operatively compared with a standard sodium hypochlorite solution (mean difference -1.70 days, 95% CI -3.41 to 0.01). This was classed as low quality evidence. There was moderate quality evidence that more open wounds resulting from excision of pyomyositis abscesses healed when treated with a honey-soaked gauze compared with a EUSOL-soaked gauze over three weeks' follow-up (RR: 1.58, 95% CI 1.03 to 2.42). There was also some evidence of a reduction in the mean length of hospital stay in the honey group. Evidence was taken from one small study that only had 43 participants. There was moderate quality evidence that more Dermacym\u00ae-treated post-operative foot wounds in people with diabetes healed compared to those treated with iodine (RR 0.61, 95% CI 0.40 to 0.93). Again estimates came from one small study with 40 participants. There is no robust evidence on the relative effectiveness of any antiseptic/antibiotic/anti-bacterial preparation evaluated to date for use on SWHSI. Where some evidence for possible treatment effects was reported, it stemmed from single studies with small participant numbers and was classed as moderate or low quality evidence. This means it is likely or very likely that further research will have an important impact on our confidence in the estimate of effect, and may change this estimate.",
        "gold": "In November 2015 we searched for as many studies as possible that both had a randomised controlled design and looked at the use of an antibiotic or antiseptic in participants with surgical wounds healing by secondary intention. We found 11 studies which included a total of 886 participants.These all looked at different comparisons. Several different types of wounds were included. Studies looked at wounds after diabetic foot amputation, pilonidal sinus surgery, treatment of various types of abscess, surgery for haemorrhoids, complications after caesarean section and healing of openings created by operations such as colostomy. Most studies compared a range of different types of antibacterial treatments to treatments without antibacterial activity, but four compared different antibacterial treatments. Although some of the trials suggested that one treatment may be better than another, this evidence was limited by the size of the studies and the ways they were carried out and reported. All of the studies had low numbers of participants and in some cases these numbers were very small. Many of the studies did not report important information about how they were carried out, so it was difficult to tell whether the results presented were likely to be true. More, better quality, research is needed to find out the effects of antimicrobial treatments on surgical wounds which are healing by secondary intention. Assessed as up to date November 2015."
    },
    {
        "index": "cochrane-simplification-test-391",
        "sentence": "We included five randomised studies with total of 1049 women evaluating five different technique modifications during either amniocentesis (three studies) or CVS (two studies). For amniocentesis three interventions were evaluated - intramuscular progesterone, hexoprenaline and selecting high or low puncture sites for late 'blind' procedure - each intervention in a single small study. There was no conclusive evidence of benefit for any of them. The same applies for terbutaline tocolysis and use of continuous vacuum aspiration during CVS. Overall, the quality of evidence summarised in this review is not of sufficient quality to change current clinical practice. In the absence of clear evidence, the operators should continue to use methods and technique modifications with which they are most familiar with. Any randomised trials of technique modifications that are performed to high standard with adequate safety outcomes and power to detect important clinical differences would be clearly welcome.",
        "gold": "We compare the safety and accuracy of various modifications and included five randomised studies with 1049 women. For amniocentesis, studies evaluated drugs that relax the uterus (tocolytics), progesterone prophylaxis, or compared the difference in safety for different puncture sites. For CVS, one study included tocolysis prior to procedure and the other evaluated the role of continuous vacuum for aspiration of the placental tissue. None of these modifications had clinically important effects on procedure safety. Overall, we found no evidence of sufficient quality to change current clinical practice. Studies of high quality with adequate safety outcomes and power to detect important clinical differences would be clearly welcome."
    },
    {
        "index": "cochrane-simplification-test-392",
        "sentence": "We included 10 studies: four provided data for quantitative analyses (437 participants); five studies were randomised trials (1182 participants); three studies were non-RCTs (1181 participants, 8037 live births); two studies were interrupted time series (ITS) studies (1 study population of 2,242,438, 1 study unreported). Six studies were conducted in upper-middle-income countries (China, Mexico, South Africa), one study was conducted in a lower-middle-income country (Bangladesh), and three studies were conducted in a high-income country (Canada). Seven studies examined wheat flour fortified with folic acid alone or with other micronutrients. Three studies included maize flour fortified with folic acid alone or with other micronutrients. The duration of interventions ranged from two weeks to 36 months, and the ITS studies included postfortification periods of up to seven years. Most studies had unclear risk of bias for randomisation, blinding, and reporting, and low/unclear risk of bias for attrition and contamination. Neural tube defects: none of the included RCTs reported neural tube defects as an outcome. In one non-RCT, wheat flour fortified with folic acid and other micronutrients was associated with significantly lower occurrence of total neural tube defects, spina bifida, and encephalocoele, but not anencephaly, compared to unfortified flour (total neural tube defects risk ratio (RR) 0.32, 95% confidence interval (CI) 0.21 to 0.48; 1 study, 8037 births; low-certainty evidence). Folate status: pregnant women who received folic acid-fortified maize porridge had significantly higher erythrocyte folate concentrations (mean difference (MD) 238.90 nmol/L, 95% CI 149.40 to 328.40); 1 study, 38 participants; very low-certainty evidence) and higher plasma folate (MD 14.98 nmol/L, 95% CI 9.63 to 20.33; 1 study, 38 participants; very low-certainty evidence), compared to no intervention. Women of reproductive age consuming maize flour fortified with folic acid and other micronutrients did not have higher erythrocyte folate (MD -61.80 nmol/L, 95% CI -152.98 to 29.38; 1 study, 35 participants; very low-certainty evidence) or plasma folate (MD 0.00 nmol/L, 95% CI -0.00 to 0.00; 1 study, 35 participants; very low-certainty evidence) concentrations, compared to women consuming unfortified maize flour. Adults consuming folic acid-fortified wheat flour bread rolls had higher erythrocyte folate (MD 0.66 nmol/L, 95% CI 0.13 to 1.19; 1 study, 30 participants; very low-certainty evidence) and plasma folate (MD 27.00 nmol/L, 95% CI 15.63 to 38.37; 1 study, 30 participants; very low-certainty evidence), versus unfortified flour. In two non-RCTs, serum folate concentrations were significantly higher among women who consumed flour fortified with folic acid and other micronutrients compared to women who consumed unfortified flour (MD 2.92 nmol/L, 95% CI 1.99 to 3.85; 2 studies, 657 participants; very low-certainty evidence). Haemoglobin or anaemia: in a cluster-randomised trial among children, there were no significant effects of fortified wheat flour flatbread on haemoglobin concentrations (MD 0.00 nmol/L, 95% CI -2.08 to 2.08; 1 study, 334 participants; low-certainty evidence) or anaemia (RR 1.07, 95% CI 0.74 to 1.55; 1 study, 334 participants; low-certainty evidence), compared to unfortified wheat flour flatbread. Fortification of wheat flour with folic acid may reduce the risk of neural tube defects; however, this outcome was only reported in one non-RCT. Fortification of wheat or maize flour with folic acid (i.e. alone or with other micronutrients) may increase erythrocyte and serum/plasma folate concentrations. Evidence is limited for the effects of folic acid-fortified wheat or maize flour on haemoglobin levels or anaemia. The effects of folic acid fortification of wheat or maize flour on other primary outcomes assessed in this review is not known. No studies reported on the occurrence of adverse effects. Limitations of this review were the small number of studies and participants, limitations in study design, and low-certainty of evidence due to how included studies were designed and reported.",
        "gold": "We conducted the literature search in March and May 2018. We included 10 studies; four studies provided data for meta-analyses. Six studies were conducted in upper-middle-income countries (China, Mexico, South Africa), one study was conducted in a lower-middle-income country (Bangladesh), and three studies were conducted in a high-income country (Canada). Seven studies examined the effects of wheat flour fortified with folic acid alone (3 studies) or with other micronutrients (4 studies). Three studies assessed the effects of maize flour fortified with folic acid alone (1 study) or with other micronutrients (two studies). Fortification of wheat flour with folic acid may reduce the likelihood of neural tube defects (i.e. total neural tube defects and two specific types of neural tube defects, spina bifida and encephalocoele (a type of neural tube defect that affects the brain and the membranes that cover it through an opening in the skull). Fortification of wheat or maize flour with folic acid (i.e. alone or with other vitamins and minerals) may increase folate status. There was limited evidence of the effects of folic acid-fortified wheat flour on haemoglobin levels or anaemia. The effects of folic acid fortification of wheat or maize flour on other main outcomes assessed in this review is not known. No studies reported on the occurrence of adverse effects. Limitations of this review were the small number of studies and participants, and the low-certainty of evidence due to how included studies were designed and reported."
    },
    {
        "index": "cochrane-simplification-test-393",
        "sentence": "Searches identified six trials. Two trials involving 1,124,483 neonates (210 with CF) with a maximum follow up of 17 years were eligible for inclusion. Varying study designs, outcomes reported and summary measures precluded calculation of pooled estimates and only data from one study were analysed. Severe malnutrition was less common among screened participants. Compared with screened participants, the odds ratio of weight below the tenth percentile was 4.12 (95% CI 1.64 to 10.38) and for height was 4.62 (95% CI 1.69 to 12.61) in the control group. At age seven, 88% of screened participants and 75% of controls had lung function parameters within normal limits of at least 89% predicted. At diagnosis chest radiograph scores were significantly better among screened participants; 33% of screened versus 50% of control participants had Wisconsin chest X-ray (WCXR) scores over five (P = 0.097) and 24% of screened versus 45% of control participants had Brasfield chest X-ray (BCXR) scores under 21 (P = 0.042)). Over time, chest radiograph scores were worse in the screened group (WCXR P = 0.017 and BCXR P = 0.041). Results were no longer significant after adjustment for genotype, pancreatic status, and Pseudomonas aeruginosa-culture results. In screened participants colonisation with Pseudomonas aeruginosa occurred earlier. Estimates suggest diagnosis through screening is less expensive. Two randomised controlled trials assessing neonatal screening in CF were identified; data from one study were included. Nutritional benefits are apparent. Screening provides potential for better pulmonary outcomes, but confounding factors influenced long-term pulmonary prognosis of people with CF. Screening seems less expensive than traditional diagnosis.",
        "gold": "This review includes two trials with 1,124,483 babies (210 with cystic fibrosis). The trials compared newborn screening to clinical diagnosis. We were only able to analyse data from one of the trials. This trial showed that severe malnutrition was less common among screened babies. Screened babies had better chest radiograph scores at diagnosis, but these scores became worse over time. The screened babies become colonised with Pseudomonas aeruginosa earlier. Costs for screening were less than costs for traditional diagnosis."
    },
    {
        "index": "cochrane-simplification-test-394",
        "sentence": "We found five randomized trials, recruiting a total of 7314 participants and with a mean follow-up of 4.5 years. Only one trial (ACCORD) compared outcomes associated with 'lower' (< 120 mmHg) or 'standard' (< 140 mmHg) systolic blood pressure targets in 4734 participants.\u00a0Despite achieving a significantly lower BP (119.3/64.4 mmHg vs 133.5/70.5 mmHg, P < 0.0001), and using more antihypertensive medications, the only significant benefit in the group assigned to 'lower' systolic blood pressure (SBP) was a reduction in the incidence of stroke: risk ratio (RR) 0.58, 95% confidence interval (CI) 0.39 to 0.88, P = 0.009, absolute risk reduction 1.1%.\u00a0The effect of SBP targets on mortality was compatible with both a reduction and increase in risk: RR 1.05 CI 0.84 to 1.30, low quality evidence. Trying to achieve the 'lower' SBP target was associated with a significant increase in the number of other serious adverse events: RR 2.58, 95% CI 1.70 to 3.91, P < 0.00001, absolute risk increase 2.0%. Four trials (ABCD-H, ABCD-N, ABCD-2V, and a subgroup of HOT) specifically compared clinical outcomes associated with 'lower' versus 'standard' targets for diastolic blood pressure (DBP) in people with diabetes.\u00a0The total number of participants included in the DBP target analysis was 2580.\u00a0Participants assigned to 'lower' DBP had a significantly lower achieved BP: 128/76 mmHg vs 135/83 mmHg, P < 0.0001.\u00a0There was a trend towards reduction in total mortality in the group assigned to the 'lower' DBP target (RR 0.73, 95% CI 0.53 to 1.01), mainly due to a trend to lower non-cardiovascular mortality. There was no difference in stroke (RR 0.67, 95% CI 0.42 to 1.05), in myocardial infarction (RR 0.95, 95% CI 0.64 to 1.40) or in congestive heart failure (RR 1.06, 95% CI 0.58 to 1.92), low quality evidence.\u00a0End-stage renal failure and total serious adverse events were not reported in any of the trials.\u00a0A sensitivity analysis of trials comparing DBP targets < 80 mmHg (as suggested in clinical guidelines) versus < 90 mmHg showed similar results. There was a high risk of selection bias for every outcome analyzed in favor of the 'lower' target in the trials included for the analysis of DBP targets. At the present time, evidence from randomized trials does not support blood pressure targets lower than the standard targets in people with elevated blood pressure and diabetes. More randomized controlled trials are needed, with future trials reporting total mortality, total serious adverse events as well as cardiovascular and renal events.",
        "gold": "The evidence is current to October 2013. We found and analyzed five randomized trials including 7134 adult participants with type 2 diabetes and high blood pressure, 40-80 years old, who received treatment aimed to lower blood pressure to a standard compared to a lower blood pressure target and followed for 2 to 5 years to detect differences in mortality and adverse events. Four out of five studies were funded by the drug manufacturer, which had a potential of impacting the results. One study was sponsored by the National Heart, Lung, and Blood Institute (NHLBI) from the United States. The only significant benefit in the group assigned to 'lower' systolic blood pressure was a small reduction in the incidence of stroke, but with a significantly larger increase in the number of other serious adverse events. The effect of systolic blood pressure targets on mortality was compatible with both a reduction and increase in risk. There was no benefit associated with a 'lower' diastolic blood pressure target. The evidence from randomized trials available at the present time is of low quality and does not support blood pressure targets lower than the standard in people with raised blood pressure and diabetes. Further research is likely to change these results and future studies should report all outcomes that are important to patients, such as mortality and adverse events."
    },
    {
        "index": "cochrane-simplification-test-395",
        "sentence": "Fourteen trials (709 participants) met the inclusion criteria for the review. One study compared two different types of non-removable casts with no discernable difference between the groups. Seven studies (366 participants) compared non-removable casts with removable pressure-relieving devices. In five of those studies non-removable casts were associated with a statistically significant increase in the number of ulcers healed compared with the removable device (RR 1.17 95% CI 1.01 to 1.36: P value = 0.04). Two studies (98 participants) found that significantly more ulcers healed with non-removable casts than with dressings alone. Achilles tendon lengthening combined with a non-removable cast in one study resulted in significantly more healed ulcers at 7 months than non-removable cast alone (RR 2.23; 95% CI 1.32 to 3.76). More ulcers remained healed at two years in this group (RR 3.41; 95% CI 1.42 to 8.18). Other comparisons included surgical debridement of ulcers; felt fitted to the foot; felted foam dressings and none of these showed a statistically significant treatment effect in favour of the intervention. Non-removable, pressure-relieving casts are more effective in healing diabetes related plantar foot ulcers than removable casts, or dressings alone. Non-removable devices, when combined with Achilles tendon lengthening were more successful in one forefoot ulcer study than the use of a non-removable cast alone.",
        "gold": "The studies included in this review compared non-removable pressure-relieving interventions (foot casts) with other ways of relieving pressure on the ulcer site to improve healing. The comparisons included dressings alone, temporary therapeutic shoes, removable pressure-relieving devices and surgical intervention. The review found that the non-removable interventions were more effective than any of the other external pressure-relieving methods. Non-removable casts used with Achilles tendon lengthening were more successful in one forefoot ulcer study than using a non-removable cast alone."
    },
    {
        "index": "cochrane-simplification-test-396",
        "sentence": "Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I2= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I2 = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I2 = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I2 = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear. Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.",
        "gold": "We identified five eligible studies that described six interventions. These included two studies of computerised cognitive skills practice, two cognitive coping skills training programmes, one meditation intervention and one exercise intervention. All five studies included a total of 235 women who had been treated for breast cancer. The findings suggest that cognitive skills practice and cognitive coping skills training may be useful in improving patient reports and formal assessments of cognition, as well as quality of life. There was insufficient evidence to know if meditation and exercise interventions had any effect on cognition. The quality of the evidence was low. There were problems with study designs and, so, we need to be cautious about our conclusions. There is not enough good quality evidence to know if any interventions improve cognitive impairment or maintain cognitive functioning among people who have received systemic treatment for cancer. There are several ongoing trials in the field, which may provide the necessary evidence in the future."
    },
    {
        "index": "cochrane-simplification-test-397",
        "sentence": "We found 12 records referring to six trials. We included five trials, all from the 1970s, randomising 343 participants. We excluded one trial. The overall methodology and data reporting by the trials was poor. Only short-term data were available. Results from the included trials found that, in terms of global state improvement, when rated by a psychiatrist, there was no clear difference between chlorpromazine and piperacetazine (RR 0.90, 95% CI 0.80 to 1.02; participants = 208; studies = 2; very low-quality evidence). One trial reported change scores on the mental state scale Brief Psychiatric Rating Scale (BPRS); no clear difference was observed (MD -0.40, 95% CI -1.41 to 0.61; participants = 182; studies = 1; very low-quality evidence). Chlorpromazine appears no worse or better than piperacetazine regarding adverse effects. In both treatment groups, around 60% of participants experienced some sort of adverse effect (RR 1.00, 95% CI 0.75 to 1.33; participants = 74; studies = 3; very low-quality evidence), with approximately 40% of these participants experiencing some parkinsonism-type movement disorder (RR 0.95, CI 0.61 to 1.49; participants = 106; studies = 3; very low-quality evidence). No clear difference in numbers of participants leaving the study early for any reason was observed (RR 0.50, 95% CI 0.10 to 2.56; participants = 256; studies = 4; very low-quality evidence). No trial reported data for change in negative symptoms or economic costs. The results of this review show chlorpromazine and piperacetazine may have similar clinical efficacy, but data are based on very small numbers of participants and the evidence is very low quality. We can not make firm conclusions based on such data. Currently, should clinicians and people with schizophrenia need to choose between chlorpromazine and piperacetazine they should be aware there is no good quality evidence to base decisions. More high quality research is needed.",
        "gold": "A search for randomised controlled trials that could be relevant to this review was carried out on 6 June 2015, and another search was carried out 8 October 2018. This was achieved by searching the Specialised Register of Cochrane Schizophrenia. The 2015 search found six possible trials and we carefully checked these to see if we could include them in the review. The 2018 search found no new trials. Five trials, randomising a total of 343 participants met the review requirements for inclusion. These trials randomly allocated participants to receive either chlorpromazine or piperacetazine. Data were reported for participants' global and mental state after treatment, incidence of adverse effects and numbers leaving the trial early. However, we did not find any data concerning service use, functioning of participants or economic costs of these treatments. The overall results showed chlorpromazine and piperacetazine may have similar clinical efficacy and side effect profiles. However, these results are based on very low-quality data. The number of included studies and the sample size of participants included in this review is small, and the quality of data very low, so the results of this review are not conclusive and must be used with caution. Further research would be needed before decisions can be made regarding which drug is more effective."
    },
    {
        "index": "cochrane-simplification-test-398",
        "sentence": "Five randomised trials were identified with a total of 207 participants, 102 to colorectal stenting and 105 to emergency surgery. There was statistically significant higher clinical success rate in the emergency surgery group. The average time of clinical relief of obstruction was 0.66 day in the colonic stent group and was 3.55 days in the emergency surgery group. The stent insertion was successful in 86.02% of attempted stent placements. There was no statistically significant difference in the 30-day mortality between two groups. The 30 day mortality rate was similar, 2.3% in both groups. The stent related perforation rate was 5.88%. The stent migration rate was 2.13%. The stent obstruction rate was 2.13%. There was no statistically significant difference in overall complication rate in both groups. The complication rate was 39.22% in the colonic stent group and was 45.71% in the emergency surgery group. The mean hospital stay was 11.53 days in the colonic stent group and was 17.15 days in the emergency surgery group. The mean procedure/operating time was 113.93 minutes in the colonic stent group compared to 143.85 minutes in the emergency surgery group. The median blood loss was 50 ml in the colonic stent group and 350 ml in the emergency surgery group. The use of colonic stent in malignant colorectal obstruction seems to have no advantage over emergency surgery. The clinical success rate was statistically higher in emergency surgery group. However, use of colorectal stents seems to be as safe in the malignant colorectal obstruction as the emergency surgery with no statistically significant difference in the mortality and morbidity. Colorectal stents are associated with acceptable stent perforation, migration and obstruction rates. The advantages of colorectal stent includes shorter hospital stay and procedure time and less blood loss. However, due to the variability in the sample size and trial designs in the included studies, further randomised trials with bigger sample size and well defined trial design are needed to achieve the robust evidence.",
        "gold": "This systematic review of five randomised trial shows higher rates of clinical relief of obstruction in emergency surgery. Colonic stent has not been shown to be as effective as emergency surgery in malignant colorectal obstructions. However, use of colonic stent is associated with comparable mortality and morbidity with advantage of shorter hospital stay and procedure time and less blood loss. Further randomised controlled trials with larger sample size and robust trial design are required on this topic."
    },
    {
        "index": "cochrane-simplification-test-399",
        "sentence": "We included nine RCTs (1867 women) comparing human albumin (seven RCTs) or HES (two RCTs) or mannitol (one RCT) versus placebo or no treatment for prevention of OHSS. The evidence was very low to moderate quality for all comparisons. The main limitations were imprecision, poor reporting of study methods, and failure to blind outcome assessment. There was evidence of a beneficial effect of intravenous albumin on OHSS, though heterogeneity was substantial (Peto OR 0.67 95% CI 0.47 to 0.95, seven studies, 1452 high risk women; I\u00b2 = 69%, very low quality evidence) . This suggests that if the rate of moderate or severe OHSS with no treatment is 12%, it will be about 9% (6% to12%) with the use of intravenous albumin. However, there was evidence of a detrimental effect on pregnancy rates (Peto OR 0.72 95% CI 0.55 to 0.94, I\u00b2 = 42%, seven studies 1069 high risk women, moderate quality evidence). This suggests that if the chance of pregnancy is 40% without treatment, it will be about 32% (27% to 38%) with the use of albumin. There was evidence of a beneficial effect of HES on OHSS (Peto OR 0.27 95% CI 0.12 to 0.59, I\u00b2 = 0%, two studies, 272 women, very low quality evidence). This suggests that if the rate of moderate or severe OHSS with no treatment is 16%, it will be about 5% (2% to 10%) with the use of HES. There was no evidence of an effect on pregnancy rates (Peto OR 1.20 95% CI 0.49 to 2.93, one study, 168 women, very low quality evidence). There was evidence of a beneficial effect of mannitol on OHSS (Peto OR 0.38, 95% CI 0.22 to 0.64, one study, 226 women with PCOS, low quality evidence). This means that if the risk of moderate or severe OHSS with no treatment is 52%, it will be about 29% (19% to 41%) with mannitol. There was no evidence of an effect on pregnancy rates (Peto OR 0.85 95% CI 0.47 to 1.55; one study, 226 women, low quality evidence). Live birth rates were not reported in any of the studies. Adverse events appeared to be uncommon, but were too poorly reported to reach any firm conclusions. Evidence suggests that the plasma expanders assessed in this review (human albumin, HES and mannitol) reduce rates of moderate and severe OHSS in women at high risk. Adverse events appear to be uncommon, but were too poorly reported to reach any firm conclusions, and there were no data on live birth. However, there was evidence that human albumin reduces pregnancy rates. While there was no evidence that HES, or mannitol had any influence on pregnancy rates, the evidence of effectiveness was based on very few trials which need to be confirmed in additional, larger randomised controlled trials (RCTs) before they should be considered for routine use in clinical practice.",
        "gold": "We found nine randomised controlled trials (RCTs) which compared the use of volume expanders (albumin, HES and mannitol) for preventing moderate or severe OHSS. Control groups received no treatment or placebo. The studies included 1867 women at high risk of OHSS. The evidence is current to September 2015. Evidence suggests that plasma expanders (human albumin, HES and mannitol) reduce rates of moderate and severe OHSS in women at high risk. If the rate of OHSS without treatment is 12%, it will be about 9% (6% to 12%) with the use of intravenous albumin. If the rate of OHSS without treatment is 16%, it will be about 5% (2% to 10%) with the use of HES, and if the rate without treatment is 52%, it will be about 29% (19% to 41%) with mannitol. Adverse events appear to be uncommon, but were too poorly reported to reach firm conclusions. No studies reported live birth, but there was evidence that human albumin reduces pregnancy rates. While there was no evidence that HES, or mannitol had any influence on pregnancy rates, the evidence of effectiveness was based on very few trials, and better evidence is needed before they should be considered for routine use in clinical practice. The evidence was very low to moderate quality for all comparisons. The main limitations were imprecision, poor reporting of study methods, and failure to blind outcome assessment."
    },
    {
        "index": "cochrane-simplification-test-400",
        "sentence": "Ten studies involving 484 patients were included. There was no evidence suggesting superior efficacy of any one sclerosant over another, but there was evidence of superiority of sclerotherapy to placebo. The evidence did not suggest an increase in patient satisfaction with any one agent versus another, but there was evidence that patients were less satisfied with placebo. There was some evidence suggesting that polidocanol (POL) was more likely to cause adverse reactions at a concentration of 1% compared with lower concentrations or hypertonic saline, and that sodium tetradecyl sulfate (STS) was more likely to cause adverse reactions at a concentration of 1% compared with POL at 0.5%. There was some evidence suggesting that STS was more painful than POL, heparsal (20% saline mixed with heparin 100 units/mL) or placebo, and that POL was no more painful than placebo. Evidence from one study suggested that hypertonic saline (HS) was more painful than POL. The data were not suitable for meta-analysis. The evidence did not suggest superior efficacy or patient satisfaction for any one sclerosing agent used in the treatment of telangiectasias of the lower limbs, but the agents studied showed superiority to a normal saline placebo. However, the amount of available evidence in this field is small and the overall methodological quality of the research was poor, as was the quality of reporting. More research is needed to determine the optimal agent(s) and the ideal dosing to achieve the best results and maximize patient satisfaction. Future research efforts should incorporate more demographic data and symptom measures to allow for comparison with findings from observational studies, thereby aiding assessment of how various risk groups respond to treatment.",
        "gold": "We included 10 randomised controlled trials involving 484 people in our review. Sodium tetradecyl sulfate (STS), polidocanol (POL), and heparsal (20% saline mixed with heparin 100 units/mL) cleared the veins more effectively than an injection of normal saline. There was no evidence that one agent was better than any other sclerosant, that patients were more satisfied with one agent than another, and which dose of an agent was best. There was some evidence that POL was less painful than heparsal and STS, and that STS was more painful than heparsal. At higher doses, some of the agents appeared to cause more pain and side effects such as mild brown discoloration, a flare or blush next to the injected vein, or itching; however, we do not have enough evidence to determine the optimal concentration to use. The trials were designed in very different ways and used various agents, which meant we were unable to combine the studies to help form firm conclusions. The amount of available evidence was limited and the overall methodological quality of the research was poor, as was the quality of reporting."
    },
    {
        "index": "cochrane-simplification-test-401",
        "sentence": "We included seven studies (241 participants) in this review. Meta-analysis of these seven included studies was not possible due to heterogeneity of the treatments and because many of the studies did not provide sufficient statistical information with their results. Allocation and blinding methodology was poorly described in most studies. No study evaluated the efficacy of pharmacological interventions for preventing clinically relevant outcomes such as mortality and cardiac arrhythmias; however there is evidence that several commonly used therapies effectively reduce serum potassium levels. Salbutamol administered via either nebulizer or metered-dose inhaler (MDI) significantly reduced serum potassium compared with placebo. The peak effect of 10 mg nebulised salbutamol was seen at 120 minutes (MD -1.29 mmol/L, 95% CI -1.64 to -0.94) and at 90 minutes for 20 mg nebulised salbutamol (1 study: MD -1.18 mmol/L, 95% CI -1.54 to -0.82). One study reported 1.2 mg salbutamol via MDI 1.2 mg produced a significant decrease in serum potassium beginning at 10 minutes (MD -0.20 mmol/L, P < 0.05) and a maximal decrease at 60 minutes (MD -0.34 mmol/L, P < 0.0001). Intravenous (IV) and nebulised salbutamol produced comparable effects (2 studies). When compared to other interventions, salbutamol had similar effect to insulin-dextrose (2 studies) but was more effective than bicarbonate at 60 minutes (MD -0.46 mmol/L, 95% CI -0.82 to -0.10; 1 study). Insulin-dextrose was more effective than IV bicarbonate (1 study) and aminophylline (1 study). Insulin-dextrose, bicarbonate and aminophylline were not studied in any placebo-controlled studies. None of the included studies evaluated the effect of IV calcium or potassium binding resins in the treatment of hyperkalaemia. Evidence for the acute pharmacological management of hyperkalaemia is limited, with no clinical studies demonstrating a reduction in adverse patient outcomes. Of the studied agents, salbutamol via any route and IV insulin-dextrose appear to be most effective at reducing serum potassium. There is limited evidence to support the use of other interventions, such as IV sodium bicarbonate or aminophylline. The effectiveness of potassium binding resins and IV calcium salts has not been tested in RCTs and requires further study before firm recommendations for clinical practice can be made.",
        "gold": "We searched for all studies that tested whether therapies were effective and safe at treating high potassium published up to 18 August 2015. We found seven studies that investigated drug therapies for treating hyperkalaemia in adults which together included results from 241 participants. Most studies tested the therapies in male and female adults with kidney problems who were medically stable. We did not find any studies that looked at the serious medical complications of high potassium such as death. We found that salbutamol and insulin-dextrose were effective in reducing potassium levels in the blood. We found that salbutamol was effective whether it was given intravenously or by nebuliser. Those treatments appeared to be more effective than other treatments such as sodium bicarbonate and aminophylline. None of the studies found any serious adverse reactions to the medications. Overall, the quality of evidence was assessed as poor because the studies were small in size and the methods for how the studies were performed were not well described. None of the studies looked at the serious problems caused by hyperkalaemia and this limited the strength of the evidence."
    },
    {
        "index": "cochrane-simplification-test-402",
        "sentence": "Thirty-nine studies, enrolling 4216 participants, were included in this review, however only 30 studies, involving 3392 participants, contained enough data to be meta-analysed. Risk of bias was low or unclear for most domains in the majority of the included studies. Studies compared antimicrobial lock solutions (antibiotic and non-antibiotic) to standard sealing solutions (usually heparin) of the CVC for HD. Fifteen studies used antibiotic lock solutions, 21 used non-antibiotic antimicrobial lock solutions, and 4 used both (antibiotic and non-antibiotic) lock solutions. Studies reported the incidence of CRI, catheter thrombosis, or both. Antimicrobial lock solutions probably reduces CRI per 1000 catheter-days (27 studies: RR 0.38, 95% CI 0.27 to 0.53; I2 = 54%; low certainty evidence), however antimicrobial lock solutions probably makes little or no difference to the risk of thrombosis per 1000 catheter days (14 studies: RR 0.79, 95% CI 0.52 to 1.22; I2 = 83%; very low certainty evidence). Subgroup analysis of antibiotic and the combination of both lock solutions showed that both probably reduced CRI per 1000 catheter-days (13 studies: RR 0.30, 95% CI: 0.22 to 0.42; I2 = 47%) and risk of thrombosis per 1000 catheter-days (4 studies: RR 0.26, 95% CI: 0.14 to 0.49; I2 = 0%), respectively. Non-antibiotic antimicrobial lock solutions probably reduced CRI per 1000 catheter-days for tunnelled CVC (9 studies: RR 0.60, 95% CI 0.40 to 0.91) but probably made little or no difference with non-tunnelled CVC (4 studies: RR 0.93, 95% CI 0.48 to 1.81). Subgroup analyses showed that antibiotic (5 studies: RR 0.76, 95% CI 0.42 to 1.38), non-antibiotic (8 studies: RR 0.85, 95% CI 0.44 to 1.66), and the combination of both lock solutions (3 studies: RR 0.63, 95% CI 0.22 to 1.81) made little or no difference to thrombosis per 1000 catheter-days compared to control lock solutions. Antibiotic antimicrobial and combined (antibiotic-non antibiotic) lock solutions decreased the incidence of CRI compared to control lock solutions, whereas non-antibiotic lock solutions reduce CRI only for tunnelled CVC. The effect on thrombosis incidence is uncertain for all antimicrobial lock solutions. Our confidence in the evidence is low and very low; therefore, better-designed studies are needed to confirm the efficacy and safety of antimicrobial lock solutions.",
        "gold": "We included 39 studies, including 3,945 participants undergoing HD through a CVC. The studies compared CVC sealing solutions with heparin to antimicrobial lock solutions. Fifteen studies used only antibiotic lock solutions, 21 used non-antibiotic lock solutions, and 4 used both (antibiotic and non-antibiotic) lock solutions. Studies measured the incidence of CRIs and catheter thrombosis, or both. Overall quality of the studies was low for CRIs and very low for thrombosis. There was no information on funding sources for most of the studies. In general antimicrobial lock solutions are likely superior to standard solutions in preventing CRIs among patients undergoing HD through a CVC, but non-antibiotic solutions did not prove to reduce CRI. They are no worse than heparin at preventing thrombosis. Other adverse effects were not reported in most studies. Our confidence in these results is low due to the quality of the studies. Some antimicrobial (antibiotic and the combination of antibiotic-non antibiotic) lock solutions decrease the incidence of CRIs compared to heparin. Their effect on CVC permeability remains unclear. The quality of the studies is low and very low, respectively; therefore, more studies are needed to confirm the benefits and harms of antimicrobial lock solutions."
    },
    {
        "index": "cochrane-simplification-test-403",
        "sentence": "We identified 15 eligible studies (1098 participants). Of these, six investigated pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), eight looked at pre-emptive treatment versus antiviral prophylaxis, and one reported on oral versus intravenous pre-emptive treatment. Assessment of risk of bias identified that the processes reported for sequence generation and allocation concealment were at low risk of bias in only five and three studies, respectively. All studies were considered to be at low risk of attrition bias, and seven studies were considered to be at low risk of bias for selective reporting. Only one study reported adequate blinding of participants and personnel; no study reported blinding of outcome assessment. Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (6 studies, 288 participants: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (3 studies, 185 participants: RR 1.21, 95% CI 0.69 to 2.12) or all-cause mortality (3 studies, 176 participants: RR 1.23, 95% CI 0.35 to 4.30). Comparative studies of pre-emptive therapy versus prophylaxis showed no significant differences in preventing CMV disease between pre-emptive and prophylactic therapy (7 studies, 753 participants: RR 1.00, 95% CI 0.36 to 2.74) but there was significant heterogeneity (I\u00b2 = 63%). Leucopenia was significantly less common with pre-emptive therapy compared with prophylaxis (6 studies, 729 participants: RR 0.42, 95% CI 0.20 to 0.90). Other adverse effects did not differ significantly or were not reported. There were no significant differences in the risks of all-cause mortality, graft loss, acute rejection and infections other than CMV. Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care. Despite the inclusion of five additional studies in this update, the efficacy of pre-emptive therapy compared with prophylaxis to prevent CMV disease remains unclear due to significant heterogeneity between studies. Additional head-to-head studies are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.",
        "gold": "This review looked at the benefits and harms of pre-emptive treatment with antiviral agents in preventing CMV disease in solid organ transplant recipients. We identified six studies (288 participants) that compared pre-emptive treatment with placebo or usual care. Pre-emptive treatment significantly reduced the risk of CMV disease. There were also eight studies (784 participants) that compared pre-emptive treatment with antiviral prophylaxis. There were no significant differences in the risks of CMV disease or death between pre-emptive therapy and prophylaxis. However, variation in results among studies meant that there is some uncertainty about these results. Low white blood cell counts were much less common with pre-emptive treatment. More studies comparing pre-emptive treatment with antiviral prophylaxis are still required to provide greater certainty about the relative effectiveness of pre-emptive therapy compared with prophylaxis."
    },
    {
        "index": "cochrane-simplification-test-404",
        "sentence": "Three RCTs met our inclusion criteria: these investigated a total of 140 participants and ranged from six weeks to five months in duration. All three studies were performed by the same trialist. Overall, the risk of bias of these trials was unclear or high. All RCTs compared the effect of sweet potato preparations with placebo on glycaemic control in type 2 diabetes mellitus. There was a statistically significant improvement in glycosylated haemoglobin A1c (HbA1c) at three to five months with 4 g/day sweet potato preparation compared to placebo (mean difference -0.3% (95% confidence interval -0.6 to -0.04); P = 0.02; 122 participants; 2 trials). No serious adverse effects were reported. Diabetic complications and morbidity, death from any cause, health-related quality of life, well-being, functional outcomes and costs were not investigated. There is insufficient evidence about the use of sweet potato for type 2 diabetes mellitus. In addition to improvement in trial methodology, issues of standardization and quality control of preparations - including other varieties of sweet potato - need to be addressed. Further observational trials and RCTs evaluating the effects of sweet potato are needed to guide any recommendations in clinical practice.",
        "gold": "We decided to investigate whether there is enough evidence from medical trials to show whether sweet potato works as a treatment for diabetes. This review of randomised controlled trials found only three studies (with a total of 140 participants) that evaluated the effects of sweet potato for type 2 diabetes mellitus compared with a fake medicine (placebo). All these trials were of very low quality. Two studies with 122 participants showed improved long-term metabolic control of blood sugar levels as measured by glycosylated haemoglobin A1c (HbA1c) which was moderately lowered by 0.3% in participants who were given 4 g sweet potato tablets a day for three to five months. The duration of treatment ranged from six weeks to five months. No study investigated diabetic complications, death from any cause, health-related quality of life, well-being, functional outcomes or costs. Adverse effects were mostly mild, and included abdominal distension and pain. There are many varieties of sweet potatoes and sweet potato preparations. More trials are needed to assess the quality of the various sweet potato preparations as well as to evaluate further the use of different varieties of sweet potato in the diet of diabetic people."
    },
    {
        "index": "cochrane-simplification-test-405",
        "sentence": "Our search identified 62 studies, of which 19 (440 participants) met the inclusion criteria. Five randomised controlled studies (192 participants) were included in the meta-analysis; three were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 22.33 years). In 13 studies, follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis. Included studies compared the active cycle of breathing technique with autogenic drainage, airway oscillating devices, high frequency chest compression devices, conventional chest physiotherapy, and positive expiratory pressure. Preference of technique varied: more participants preferred autogenic drainage over the active cycle of breathing technique; more preferred the active cycle of breathing technique over airway oscillating devices; and more were comfortable with the active cycle of breathing technique versus high frequency chest compression. No significant difference was seen in quality of life, sputum weight, exercise tolerance, lung function, or oxygen saturation between the active cycle of breathing technique and autogenic drainage or between the active cycle of breathing technique and airway oscillating devices. There was no significant difference in lung function and the number of pulmonary exacerbations between the active cycle of breathing technique alone or in conjunction with conventional chest physiotherapy. All other outcomes were either not measured or had insufficient data for analysis. There is insufficient evidence to support or reject the use of the active cycle of breathing technique over any other airway clearance therapy. Five studies, with data from eight different comparators, found that the active cycle of breathing technique was comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of the active cycle of breathing technique on outcomes important for people with cystic fibrosis such as quality of life and preference.",
        "gold": "While 19 studies comparing the active cycle of breathing technique with other airway clearance therapies are included in the review, only five studies (192 participants) reported data that we could include in the analysis. Each of the five studies compared different techniques: the active cycle of breathing technique was compared with autogenic drainage, airway oscillating devices, high-frequency chest compression devices, positive expiratory pressure, and conventional chest physiotherapy. Most studies lasted a single day, but there were two studies that lasted between one and three years. Participants ranged in age from six to 63 years and most (63%) were male. We found that the active cycle of breathing technique was comparable with other treatments in outcomes such as quality of life, personal preference, exercise tolerance, lung function, sputum weight, oxygen saturation, and the number of pulmonary exacerbations. We were not able to show that any single technique was better than another. Longer studies are needed to better assess the effects of the active cycle of breathing technique on outcomes important for people with cystic fibrosis such as quality of life and personal preference. Many of the studies did not provide enough details of their methods to determine if there were any biases that might have affected the results. Many studies did not report how they decided who would get which treatment and how they made sure that the people who were putting people into the different treatment groups and those who were assessing the results did not know which group each individual was in. Most of the included studies had a cross-over design (where people have one treatment and then switch to the second), and many of these did not report the length of time in between different treatments. As it is possible that the first treatment might affect the results of the next treatment, we only included results from the first treatment period. Many of the studies did not report separate results for just the first treatment period, so we did not include their results in our review. All participants knew which treatment group they were in (it is not possible to disguise different physiotherapy techniques). This could have affected the results for some of the self-reported outcomes, such as quality of life, personal preference, or exercise tolerance, but is unlikely to have affected the more objective outcomes, such as lung function. Most of the studies followed those taking part for less than one month and did this for most of the participants for the entire study period. In two out of the three longer studies more than 10% of the people taking part dropped out. The study results could be affected if the people who dropped out of the studies were not evenly spread across the different treatment groups. Over half of the studies checked that participants were using the airway clearance therapy they were supposed to. Most of the studies reported on all their planned outcomes. The findings of the review were limited as not many studies made the same comparisons; also, there were not many long-term studies and the studies we included did not report enough data."
    },
    {
        "index": "cochrane-simplification-test-406",
        "sentence": "Eight RCTs with 733 women in total that compared brief co-incubation and the standard insemination protocol were included. Live birth was not reported in the included studies. For ongoing pregnancy rate, there were 127 ongoing pregnancies in two trials including 426 women. The low quality evidence showed that brief co-incubation was associated with an increased ongoing pregnancy rate compared to the standard insemination protocol (pooled odds ratio (OR) 2.42, 95% confidence interval (CI) 1.55 to 3.77; P < 0.0001, I2 = 0%). Measuring clinical pregnancy rate, there were 93 clinical pregnancies in three trials including 372 women. The low quality evidence\u00a0showed that brief co-incubation was associated with a significantly higher clinical pregnancy rate than the overnight insemination protocol (pooled OR 2.36, 95% CI 1.45 to 3.85; P = 0.0006, I2 = 0%). For the miscarriage rate, there were six miscarriages in one trial including 167 women. This low quality evidence suggested no significant difference in the odds of miscarriage between brief co-incubation and standard insemination (OR 1.98, 95% CI 0.35 to 11.09; P = 0.44). This review has provided evidence that brief co-incubation of sperm and oocytes may improve the ongoing pregnancy and clinical pregnancy rates for infertile women undergoing IVF cycles. More RCTs are required to assess whether brief co-incubation would contribute to a higher live birth rate and a lower miscarriage rate compared to the standard overnight insemination protocol.",
        "gold": "This review identified eight randomized controlled trials involving 733 women. Low quality evidence showed increases in ongoing pregnancy and clinical pregnancy rates with the use of the brief co-incubation protocol. More studies are needed to assess whether brief co-incubation would contribute to a higher live-birth rate and a lower miscarriage rate compared to the standard overnight insemination protocol."
    },
    {
        "index": "cochrane-simplification-test-407",
        "sentence": "In five studies, recruiting a total of 694 infants, a long IT was associated with a significant increase in air leak [typical RR 1.56 (1.25, 1.94), RD 0.13 (0.07, 0.20), NNT 8 (5, 14)]. There was no significant difference in the incidence of BPD. Long IT was associated with an increase in mortality before hospital discharge that reached borderline statistical significance [typical RR 1.26 (1.00, 1.59), RD 0.07 (0.00, 0.13)]. Caution should be exercised in applying these results to modern neonatal intensive care, because the studies included in this review were conducted prior to the introduction of antenatal steroids, post natal surfactant and the use of synchronised modes of ventilatory support. Most of the participants had single pathology (HMD) and no studies examined the effects of IT on newborns ventilated for other reasons such as meconium aspiration and congenital heart disease (lungs with normal compliance). However, the increased rates of air leaks and deaths using long ITs are clinically important; thus, infants with poorly compliant lungs should be ventilated with a short IT.",
        "gold": "The review authors identified five randomised studies reported from 1980 to 1992. These trials recruited a total of 694 newborn infants with acute respiratory failure mainly caused by hyaline membrane disease. A long inspiratory time was associated with a significant increase in air leak from the lungs (NNT 8). There was no significant difference in the incidence of BPD but an increase in mortality before hospital discharge reached borderline statistical significance. Caution should be exercised in applying these results to modern neonatal intensive care because these studies were conducted before the introduction of antenatal steroids, postnatal surfactant and the use of synchronised modes of ventilatory support. Whilst there is increasing use of non-invasive ventilation such as nasal continuous positive airway pressure to avoid ventilator-induced lung injury, mechanical ventilation will continue to have a role in extremely immature infants and those with hyaline membrane disease complicated by apnea."
    },
    {
        "index": "cochrane-simplification-test-408",
        "sentence": "We included 33 studies involving 5110 patients. Predominantly, the studies were of low methodological quality. TFU has been applied in many patient groups. There is a large variety in the ways the TFU was performed (the health professionals who undertook the TFU, frequency, structure, duration, etc.). Many different outcomes have been measured, but only a few were measured across more than one study. Effects are not constant across studies, nor within patient groups. Due to methodological and clinical diversity, quantitative pooling could only be performed for a few outcomes. Of the eight meta-analyses in this review, five showed considerable statistical heterogeneity. Overall, there was inconclusive evidence about the effects of TFU. The low methodological quality of the included studies means that results must be considered with caution. No adverse effects were reported. Nevertheless, although some studies find that the intervention had favourable effects for some outcomes, overall the studies show clinically-equivalent results between TFU and control groups. In summary, we cannot conclude that TFU is an effective intervention.",
        "gold": "Our systematic review identified 33 relevant studies, almost all of which were of low methodological quality (a major limitation of the review). We found that telephone follow-up has been applied in many patient groups. There is great variety in the ways the telephone follow-up has been performed. Many different outcomes have been measured. Some studies found effects in favour of the telephone follow-up intervention, but overall studies identified no statistically significant differences between the telephone follow-up and control groups. For as far as the results of studies could be pooled together, we could draw no firm conclusions about the effects of telephone follow-up. No studies identified adverse effects of the intervention."
    },
    {
        "index": "cochrane-simplification-test-409",
        "sentence": "We identified 38 eligible retention trials. Included trials evaluated six broad types of strategies to improve retention. These were incentives, communication strategies, new questionnaire format, participant case management, behavioural and methodological interventions. For 34 of the included trials, retention was response to postal and electronic questionnaires with or without medical test kits. For four trials, retention was the number of participants remaining in the trial. Included trials were conducted across a spectrum of disease areas, countries, healthcare and community settings. Strategies that improved trial retention were addition of monetary incentives compared with no incentive for return of trial-related postal questionnaires (RR 1.18; 95% CI 1.09 to 1.28, P value < 0.0001), addition of an offer of monetary incentive compared with no offer for return of electronic questionnaires (RR 1.25; 95% CI 1.14 to 1.38, P value < 0.00001) and an offer of a GBP20 voucher compared with GBP10 for return of postal questionnaires and biomedical test kits (RR 1.12; 95% CI 1.04 to 1.22, P value < 0.005). The evidence that shorter questionnaires are better than longer questionnaires was unclear (RR 1.04; 95% CI 1.00 to 1.08, P value = 0.07) and the evidence for questionnaires relevant to the disease/condition was also unclear (RR 1.07; 95% CI 1.01 to 1.14). Although each was based on the results of a single trial, recorded delivery of questionnaires seemed to be more effective than telephone reminders (RR 2.08; 95% CI 1.11 to 3.87, P value = 0.02) and a 'package' of postal communication strategies with reminder letters appeared to be better than standard procedures (RR 1.43; 95% CI 1.22 to 1.67, P value < 0.0001). An open trial design also appeared more effective than a blind trial design for return of questionnaires in one fracture prevention trial (RR 1.37; 95% CI 1.16 to 1.63, P value = 0.0003). There was no good evidence that the addition of a non-monetary incentive, an offer of a non-monetary incentive, 'enhanced' letters, letters delivered by priority post, additional reminders, or questionnaire question order either increased or decreased trial questionnaire response/retention. There was also no evidence that a telephone survey was either more or less effective than a monetary incentive and a questionnaire. As our analyses are based on single trials, the effect on questionnaire response of using offers of charity donations, sending reminders to trial sites and when a questionnaire is sent, may need further evaluation. Case management and behavioural strategies used for trial retention may also warrant further evaluation. Most of the retention trials that we identified evaluated questionnaire response. There were few evaluations of ways to improve participants returning to trial sites for trial follow-up. Monetary incentives and offers of monetary incentives increased postal and electronic questionnaire response. Some other strategies evaluated in single trials looked promising but need further evaluation. Application of the findings of this review would depend on trial setting, population, disease area, data collection and follow-up procedures.",
        "gold": "This review identified methods that encouraged people to stay in trials. We searched scientific databases for randomised studies (where people are allocated to one of two or more possible treatments in a random manner) or quasi-randomised studies (where allocation is not really random, e.g. based on date of birth, order in which they attended clinic) that compared methods of increasing retention in trials. We included trials of participants from any age, gender, ethnic, cultural, language and geographic groups. The methods that appeared to work were offering or giving a small amount of money for return of a completed questionnaire and enclosing a small amount of money with a questionnaire with the promise of a further small amount of money for return of a filled in questionnaire. The effect of other ways to keep people in trials is still not clear and more research is needed to see if these really do work. Such methods are shorter questionnaires, sending questionnaires by recorded delivery, using a trial design where people know which treatment they will receive, sending specially designed letters with a reply self addressed stamped envelope followed by a number of reminders, offering a donation to charity or entry into a prize draw, sending a reminder to the study site about participants to follow-up, sending questionnaires close to the time the patient was last followed-up, managing peoples' follow-up, conducting follow-up by telephone and changing the order of questionnaire questions. The methods that we identified were tested in trials run in many different disease areas and settings and, in some cases, were tested in only one trial. Therefore, more studies are needed to help decide whether our findings could be used in other research fields."
    },
    {
        "index": "cochrane-simplification-test-410",
        "sentence": "We included eight RCTs that involved a total of 829 participants (416 and 413 participants in the pLMA and cLMA groups, respectively). We identified six cross-over studies that are awaiting classification; one is completed but has not been published, and data related to the first treatment period for the other five studies were not yet available. Seven included studies provided data related to the primary outcome, and eight studies provided data related to more than one secondary outcome. Our analysis was hampered by the fact that a large proportion of the included studies reported no events in either study arm. No studies reported significant differences between devices in relation to the primary review outcome: failure to adequately mechanically ventilate. We evaluated this outcome by assessing two variables: inadequate oxygenation (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.17 to 3.31; four studies, N = 617) and inadequate ventilation (not estimable; one study, N = 80). More time was required to establish an effective airway using pLMA (mean difference (MD) 10.12 seconds, 95% CI 5.04 to 15.21; P < 0.0001; I\u00b2 = 73%; two studies, N = 434). Peak airway pressure during positive pressure ventilation was lower in cLMA participants (MD 0.84, 95% CI 0.02 to 1.67; P = 0.04; I\u00b2 = 0%; four studies, N = 259). Mean oropharyngeal leak (OPL) pressure was higher in pLMA participants (MD 6.93, 95% CI 4.23 to 9.62; P < 0.00001; I\u00b2 = 87%; six studies, N = 709). The quality of evidence for all outcomes, as assessed by GRADE score, is low mainly owing to issues related to blinding and imprecision. Data show no important differences between devices with regard to failure to insert the device, use of an alternate device, mucosal injury, sore throat, bronchospasm, gastric insufflation, regurgitation, coughing, and excessive leak. Data were insufficient to allow estimation of differences for obstruction related to the device. None of the studies reported postoperative nausea and vomiting as an outcome. We are uncertain about the effects of either of the airway devices in terms of failure of oxygenation or ventilation because there were very few events. Results were uncertain in terms of differences for several complications. Low-quality evidence suggests that the ProSeal laryngeal mask airway makes a better seal and therefore may be more suitable than the Classic laryngeal mask airway for positive pressure ventilation. The Classic laryngeal mask airway may be quicker to insert, but this is unlikely to be clinically meaningful.",
        "gold": "We included eight randomized studies that involved a total of 829 participants 18 years of age and older. All participants had elective surgeries and needed general anaesthesia. Researchers directly compared cLMA against pLMA for providing artificial breathing during surgery. We identified six cross-over studies that are awaiting classification; one is completed but has not been published, and five other studies are gathering data related to the first treatment period that are not yet available. Five studies did not report any funding sources. Of the remaining three studies, one reported that the Laryngeal Mask Company sponsored some data but was not involved in study design, data analysis, and manuscript preparation. The Joseph Drown Foundation, in Los Angeles, Califiornia, in the USA, partially supported another study. One of the authors of the final study had received research funds from Intavent Ltd, manufacturer of both types of laryngeal mask airway, but Intavent Ltd did not sponsor this study. We are unsure whether these devices exhibit important differences in providing adequate oxygenation and ventilation because there was not enough data to enable us to draw any firm conclusions. ProSeal laryngeal mask airway may provides a better seal because it leaks at higher pressure, but Classic laryngeal mask airway may be quicker to insert. However, these findings are not important clinically. We assessed all of the included studies as providing low-quality evidence because anaesthetists knew which device was being used on which participants (although this was probably unavoidable), and because it was unclear whether the investigator who collected the data was unaware of the intervention. This fact created the potential for bias."
    },
    {
        "index": "cochrane-simplification-test-411",
        "sentence": "We included 19 RCTs, reported in 27 papers with a total of 1453 participants. Fifteen of these studies were not included in the previous review. All 19 RCTs had follow-up ranging from one to five months. Participants were aged between four and 18 years from eight different countries and were recruited largely from paediatric gastroenterology clinics. The mean age at recruitment ranged from 6.3 years to 13.1 years. Girls outnumbered boys in most trials. Fourteen trials recruited children with a diagnosis under the broad umbrella of RAP or functional gastrointestinal disorders; five trials specifically recruited only children with irritable bowel syndrome. The studies fell into four categories: trials of probiotic-based interventions (13 studies), trials of fibre-based interventions (four studies), trials of low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diets (one study), and trials of fructose-restricted diets (one study). We found that children treated with probiotics reported a greater reduction in pain frequency at zero to three months postintervention than those given placebo (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.98 to -0.12; 6 trials; 523 children). There was also a decrease in pain intensity in the intervention group at the same time point (SMD -0.50, 95% CI -0.85 to -0.15; 7 studies; 575 children). However, we judged the evidence for these outcomes to be of low quality using GRADE due to an unclear risk of bias from incomplete outcome data and significant heterogeneity. We found that children treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (odds ratio (OR) 1.63, 95% CI 1.07 to 2.47; 7 studies; 722 children). The estimated number needed to treat for an additional beneficial outcome (NNTB) was eight, meaning that eight children would need to receive probiotics for one to experience improvement in pain in this timescale. We judged the evidence for this outcome to be of moderate quality due to significant heterogeneity. Children with a symptom profile defined as irritable bowel syndrome treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (OR 3.01, 95% CI 1.77 to 5.13; 4 studies; 344 children). Children treated with probiotics were more likely to experience improvement in pain at three to six months postintervention compared to those receiving placebo (OR 1.94, 95% CI 1.10 to 3.43; 2 studies; 224 children). We judged the evidence for these two outcomes to be of moderate quality due to small numbers of participants included in the studies. We found that children treated with fibre-based interventions were not more likely to experience an improvement in pain at zero to three months postintervention than children given placebo (OR 1.83, 95% CI 0.92 to 3.65; 2 studies; 136 children). There was also no reduction in pain intensity compared to placebo at the same time point (SMD -1.24, 95% CI -3.41 to 0.94; 2 studies; 135 children). We judged the evidence for these outcomes to be of low quality due to an unclear risk of bias, imprecision, and significant heterogeneity. We found only one study of low FODMAP diets and only one trial of fructose-restricted diets, meaning no pooled analyses were possible. We were unable to perform any meta-analyses for the secondary outcomes of school performance, social or psychological functioning, or quality of daily life, as not enough studies included these outcomes or used comparable measures to assess them. With the exception of one study, all studies reported monitoring children for adverse events; no major adverse events were reported. Overall, we found moderate- to low-quality evidence suggesting that probiotics may be effective in improving pain in children with RAP. Clinicians may therefore consider probiotic interventions as part of a holistic management strategy. However, further trials are needed to examine longer-term outcomes and to improve confidence in estimating the size of the effect, as well as to determine the optimal strain and dosage. Future research should also explore the effectiveness of probiotics in children with different symptom profiles, such as those with irritable bowel syndrome. We found only a small number of trials of fibre-based interventions, with overall low-quality evidence for the outcomes. There was therefore no convincing evidence that fibre-based interventions improve pain in children with RAP. Further high-quality RCTs of fibre supplements involving larger numbers of participants are required. Future trials of low FODMAP diets and other dietary interventions are also required to facilitate evidence-based recommendations.",
        "gold": "This evidence is current to June 2016. Nineteen studies met our inclusion criteria, including 13 studies of probiotics and four studies of fibre interventions. We also found one study of a diet low in substances known as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and one study of a fructose-restricted diet. All of the studies compared dietary interventions to a placebo or control. The trials were carried out in eight countries and included a total of 1453 participants, aged between five and 18 years. Most children were recruited from outpatient clinics. Most interventions lasted four to six weeks. Probiotics We found evidence from 13 studies suggesting that probiotics might be effective in improving pain in the shorter term. Most studies did not report on other areas such as quality of daily life. No harmful effects were reported, other than dry mouth in one study. We judged this evidence to be of moderate or low quality because some studies were small, showed varying results, or were at risk of bias. Fibre supplements We found no clear evidence of improvement of pain from four studies of fibre supplements. Most studies did not report on other areas such as quality of daily life. No harmful effects were reported. There were few studies of fibre supplements, and some of these studies were at risk of bias. We judged this evidence to be of low quality. Low FODMAP diets We found only one study evaluating the effectiveness of low FODMAP diets in children with RAP. Fructose-restricted diets We found only one study evaluating the effectiveness of fructose-restricted diets in children with RAP. We found some evidence suggesting that probiotics may be helpful in relieving pain in children with RAP in the short term. Clinicians may therefore consider probiotic interventions as part of the management strategy for RAP. Further trials are needed to find out how effective probiotics are over longer periods of time and which probiotics might work best. We did not find convincing evidence that fibre supplements are effective in improving pain in children with RAP. Future larger, high-quality studies are needed to test the effectiveness of fibre and low FODMAP diet treatments."
    },
    {
        "index": "cochrane-simplification-test-412",
        "sentence": "We included 22 studies involving 4490 participants. All were randomised trials (3 were cluster RCTs), and 19 of the 22 studies had analysable outcome data. Seventeen of the studies had student populations. Most of the studies were at unclear or high risk of bias for all forms of bias except detection bias. Findings from the five trials with discrimination outcomes (n = 1196) were mixed, with effects showing a reduction, increase or consistent with no evidence of effect. The median standardised mean difference (SMD) for the three trials (n = 394) with continuous outcomes was -0.25, with SMDs ranging from -0.85 (95% confidence interval (CI) -1.39 to -0.31) to -0.17 (95% CI -0.53 to 0.20). Odds ratios (OR) for the two studies (n = 802) with dichotomous discrimination outcomes showed no evidence of effect: results were 1.30 (95% CI 0.53 to 3.19) and 1.19 (95% CI 0.85 to 1.65). The 19 trials (n = 3176) with prejudice outcomes had median SMDs favouring the intervention, at the three following time periods: -0.38 (immediate), -0.38 (1 week to 2 months) and -0.49 (6 to 9 months). SMDs for prejudice outcomes across all studies ranged from -2.94 (95% CI -3.52 to -2.37) to 2.40 (95% CI 0.62 to 4.18). The median SMDs indicate that mass media interventions may have a small to medium effect in decreasing prejudice, and are equivalent to reducing the level of prejudice from that associated with schizophrenia to that associated with major depression. The studies were very heterogeneous, statistically, in their populations, interventions and outcomes, and only two meta-analyses within two subgroups were warranted. Data on secondary outcomes were sparse. Cost data were provided on request for three studies (n = 416), were highly variable, and did not address cost-effectiveness. Two studies (n = 455) contained statements about adverse effects and neither reported finding any. Mass media interventions may reduce prejudice, but there is insufficient evidence to determine their effects on discrimination. Very little is known about costs, adverse effects or other outcomes. Our review found few studies in middle- and low-income countries, or with employers or health professionals as the target group, and none targeted at children or adolescents. The findings are limited by the quality of the evidence, which was low for the primary outcomes for discrimination and prejudice, low for adverse effects and very low for costs. More research is required to establish the effects of mass media interventions on discrimination, to better understand which types of mass media intervention work best, to provide evidence about cost-effectiveness, and to fill evidence gaps about types of mass media not covered in this review. Such research should use robust methods, report data more consistently with reporting guidelines and be less reliant on student populations.",
        "gold": "We reviewed studies comparing people who saw or heard a mass media intervention about mental health problems with people who had not seen or heard any intervention, or who had seen an intervention which contained nothing about mental ill health or stigma. We aimed to find out what effects mass media interventions may have on reducing stigma towards people with mental health problems. We found 22 studies involving 4490 people.\u00a0 Five of these studies had data about discrimination and 19 had data about prejudice. We found that mass media interventions may reduce, increase, or have no effect on discrimination. We found that mass media interventions may reduce prejudice. The amount of the reduction can be considered as small to medium, and is similar to reducing the level of prejudice from that associated with schizophrenia to that associated with major depression. The quality of the evidence about discrimination and prejudice was low, so we cannot be very certain about these findings. Only three studies gave any information about financial costs and two about adverse affects, and there were limitations in how they assessed these, so we cannot draw conclusions about these aspects."
    },
    {
        "index": "cochrane-simplification-test-413",
        "sentence": "We include 85 studies in our synthesis. Forty-six studies explored the views and experiences of healthy pregnant or postnatal women, 17 studies explored the views and experiences of healthcare providers and 22 studies incorporated the views of both women and healthcare providers. The studies took place in 41 countries, including eight high-income countries, 18 middle-income countries and 15 low-income countries, in rural, urban and semi-urban locations. We developed 52 findings in total and organised these into three thematic domains: socio-cultural context (11 findings, five moderate- or high-confidence); service design and provision (24 findings, 15 moderate- or high-confidence); and what matters to women and staff (17 findings, 11 moderate- or high-confidence) The third domain was sub-divided into two conceptual areas; personalised supportive care, and information and safety. We also developed two lines of argument, using high- or moderate-confidence findings: For women, initial or continued use of ANC depends on a perception that doing so will be a positive experience. This is a result of the provision of good-quality local services that are not dependent on the payment of informal fees and that include continuity of care that is authentically personalised, kind, caring, supportive, culturally sensitive, flexible, and respectful of women\u2019s need for privacy, and that allow staff to take the time needed to provide relevant support, information and clinical safety for the woman and the baby, as and when they need it. Women\u2019s perceptions of the value of ANC depend on their general beliefs about pregnancy as a healthy or a risky state, and on their reaction to being pregnant, as well as on local socio-cultural norms relating to the advantages or otherwise of antenatal care for healthy pregnancies, and for those with complications. Whether they continue to use ANC or not depends on their experience of ANC design and provision when they access it for the first time. The capacity of healthcare providers to deliver the kind of high-quality, relationship-based, locally accessible ANC that is likely to facilitate access by women depends on the provision of sufficient resources and staffing as well as the time to provide flexible personalised, private appointments that are not overloaded with organisational tasks. Such provision also depends on organisational norms and values that overtly value kind, caring staff who make effective, culturally-appropriate links with local communities, who respect women\u2019s belief that pregnancy is usually a normal life event, but who can recognise and respond to complications when they arise. Healthcare providers also require sufficient training and education to do their job well, as well as an adequate salary, so that they do not need to demand extra informal funds from women and families, to supplement their income, or to fund essential supplies. This review has identified key barriers and facilitators to the uptake (or not) of ANC services by pregnant women, and in the provision (or not) of good-quality ANC by healthcare providers. It complements existing effectiveness reviews of models of ANC provision and adds essential insights into why a particular type of ANC provided in specific local contexts may or may not be acceptable, accessible, or valued by some pregnant women and their families/communities. Those providing and funding services should consider the three thematic domains identified by the review as a basis for service development and improvement. Such developments should include pregnant and postnatal women, community members and other relevant stakeholders.",
        "gold": "We include 85 studies in our synthesis. Forty-six studies explored the views and experiences of women who were pregnant or who had recently given birth. 17 studies explored the views and experiences of healthcare providers, including lay or community health workers, and 22 studies included the views of both women and healthcare providers. The studies took place in eight high-income countries, 18 middle-income countries and 12 low-income countries, in rural and urban locations. Our findings suggest that women use antenatal care if they find it is a positive experience that fits with their beliefs and values, is easy for them to access, affordable, and treats them as an individual. They want care that helps them to feel that they and their baby are safe, and that is provided by kind, caring, culturally sensitive, flexible, and respectful staff that have time to give them support and reassurance about the health and well-being of them and their babies. They also value tests and treatments that are offered when they need them, and information and advice that is relevant to them. Our findings also suggest that healthcare staff want to be able to offer this kind of care. They would like to work in antenatal services that are properly funded, and that give them proper support, pay, training and education. They believe this will help them to have enough time to treat each pregnant woman as an individual, and to have the knowledge, skills resources and equipment to do their job well. The review authors searched for studies that had been published up to February 2019."
    },
    {
        "index": "cochrane-simplification-test-414",
        "sentence": "Sixteen trials, involving 3361 patients, were included in the review; three of the studies were of magnesium sulphate in addition to nimodipine. Overall, calcium antagonists reduced the risk of poor outcome: the relative risk (RR) was 0.81 (95% confidence interval (CI) 0.72 to 0.92); the corresponding number of patients needed to treat was 19 (95% CI 1 to 51). For oral nimodipine alone the RR was 0.67 (95% CI 0.55 to 0.81), for other calcium antagonists or intravenous administration of nimodipine the results were not statistically significant. Calcium antagonists reduced the occurrence of secondary ischaemia and showed a favourable trend for case fatality. For magnesium in addition to standard treatment with nimodipine, the RR was 0.75 (95% CI 0.57 to 1.00) for a poor outcome and 0.66 (95% CI 0.45 to 0.96) for clinical signs of secondary ischaemia. Calcium antagonists reduce the risk of poor outcome and secondary ischaemia after aneurysmal SAH. The results for 'poor outcome' depend largely on a single large trial of oral nimodipine; the evidence for other calcium antagonists is inconclusive. The evidence for nimodipine is not beyond all doubt, but given the potential benefits and modest risks of this treatment, oral nimodipine is currently indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended for routine practice on the basis of the present evidence. Magnesium sulphate is a promising agent but more evidence is needed before definite conclusions can be drawn.",
        "gold": "This review of 16 trials, involving 3361 patients, has found that the outcome after subarachnoid haemorrhage, in terms of survival and being independent in activities of daily living, is improved by treatment with calcium channel blockers (antagonists). If the largest trial is excluded from the analysis, the results are no longer statistically significant, and therefore the evidence is not beyond all doubt. However, given the high likelihood of benefits and the modest risks associated with this treatment, the review authors conclude that calcium antagonists, in the form of oral nimodipine 60 mg every four hours, are useful in patients with subarachnoid haemorrhage from a ruptured aneurysm. Magnesium is another calcium antagonist with promising results, but larger trials with this drug are needed before we can be certain about a beneficial effect."
    },
    {
        "index": "cochrane-simplification-test-415",
        "sentence": "We identified three RCTs including 739 children. They all used an age of one year as the cut-off point for pre-treatment risk stratification. The first updated search identified a manuscript reporting additional follow-up data for one of these RCTs, while the second update identified an erratum of this study. There was a significant statistical difference in event-free survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (three studies, 739 patients; HR 0.78, 95% CI 0.67 to 0.90). There was a significant statistical difference in overall survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (two studies, 360 patients; HR 0.74, 95% CI 0.57 to 0.98). However, when additional follow-up data were included in the analyses the difference in event-free survival remained statistically significant (three studies, 739 patients; HR 0.79, 95% CI 0.70 to 0.90), but the difference in overall survival was no longer statistically significant (two studies, 360 patients; HR 0.86, 95% CI 0.73 to 1.01). The meta-analysis of secondary malignant disease and treatment-related death did not show any significant statistical differences between the treatment groups. Data from one study (379 patients) showed a significantly higher incidence of renal effects, interstitial pneumonitis and veno-occlusive disease in the myeloablative group compared to conventional chemotherapy, whereas for serious infections and sepsis no significant difference between the treatment groups was identified. No information on quality of life was reported. In the individual studies we evaluated different subgroups, but the results were not univocal in all studies. All studies had some methodological limitations. Based on the currently available evidence, myeloablative therapy seems to work in terms of event-free survival. For overall survival there is currently no evidence of effect when additional follow-up data are included. No definitive conclusions can be made regarding adverse effects and quality of life, although possible higher levels of adverse effects should be kept in mind. A definitive conclusion regarding the effect of myeloablative therapy in different subgroups is not possible. This systematic review only allows a conclusion on the concept of myeloablative therapy; no conclusions can be made regarding the best treatment strategy. Future trials on the use of myeloablative therapy for high-risk neuroblastoma should focus on identifying the most optimal induction and/or myeloablative regimen. The best study design to answer these questions is a RCT. These RCTs should be performed in homogeneous study populations (e.g. stage of disease and patient age) and have a long-term follow-up. Different risk groups, using the most recent definitions, should be taken into account. It should be kept in mind that recently the age cut-off for high risk disease was changed from one year to 18 months. As a result it is possible that patients with what is now classified as intermediate-risk disease have been included in the high-risk groups. Consequently the relevance of the results of these studies to the current practice can be questioned. Survival rates may be overestimated due to the inclusion of patients with intermediate-risk disease.",
        "gold": "This systematic review focused on randomised studies comparing the effectiveness of myeloablative therapy with conventional therapy in children with high-risk neuroblastoma. The authors found three studies including 739 patients. These studies provide evidence that myeloablative therapy improves event-free survival (that is, the time until a certain event, for example tumour progression, the development of a second tumour, or death from any cause occurs). For overall survival (that is, the time until a patient dies from any cause, so not only from the tumour or its treatment, but for example, also from a car accident) there is no evidence of a better outcome in patients treated with myeloablative therapy. Side effects such as renal (kidney) effects, interstitial pneumonitis (a type of lung disease) and veno-occlusive disease (a condition in which some of the small veins in the liver are obstructed) were more common in patients treated with myeloablative therapy than conventional chemotherapy. It should be noted that this systematic review only allows a conclusion on the concept of myeloablative therapy; no conclusions regarding the best treatment strategy with regard to, for example, types of chemotherapeutic agents and the use of radiation therapy, could be made. More high quality research is needed. It should be noted that recently the age cut-off for high-risk disease was changed from one year to 18 months. As a result it is possible that patients with what is now classified as intermediate-risk disease were included in the high-risk groups. Consequently the relevance of the results of these studies to the current practice can be questioned. Survival rates may be overestimated due to the inclusion of patients with intermediate-risk disease."
    },
    {
        "index": "cochrane-simplification-test-416",
        "sentence": "We identified eight randomised clinical trials (632 participants) that fulfilled our inclusion criteria. All eight trials were at high risk of bias, and we rated the evidence as low to very low certainty. The mean age ranged from 16 years to 78 years. The proportion of men ranged from 60% to 75% and the proportion of people with stage III primary hepatocellular carcinoma ranged from 22% to 85%. The median follow-up duration was 12 months (2 months to 38 months). TACE followed by 3-DCRT compared with TACE alone may have reduced all-cause mortality at three years' follow-up (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.73 to 0.88; 552 participants; 7 trials; low-certainty evidence). TACE followed by 3-DCRT compared with TACE alone may reduce the proportion of participants without tumour response (complete response plus partial response) (RR 0.49, 95% CI 0.39 to 0.61; 632 participants; 8 trials; low-certainty evidence). Data, from one trial on health-related quality of life, favoured the TACE followed by 3-DCRT group, but the provided data were ill-defined (very low-certainty evidence). None of the trials reported serious adverse events. The results on non-serious adverse events were as follows: TACE followed by 3-DCRT compared with TACE alone showed no difference in the results for proportion of participants with leukopenia (RR 1.12, 95% CI 0.92 to 1.34; 438 participants; 5 trials; very low-certainty evidence) and serum transaminases elevation (RR 1.67, 95% CI 0.66 to 4.27; 280 participants; 4 trials; very low-certainty evidence). However, the proportion of participants with total bilirubin elevation was larger in the TACE followed by 3-DCRT group than in the TACE alone group (RR 2.69, 95% CI 1.34 to 5.40; 172 participants; 2 trials; very low-certainty evidence). The rate of participants with serum alpha-fetoprotein (AFP) without decline or normalisation was significantly lower in the TACE followed by 3-DCRT group than in the TACE group, but these data were from one trial only (Chi\u00b2 = 7.24, P = 0.007; very low-certainty evidence). TACE followed by 3-DCRT may be associated with lower all-cause mortality and increased tumour response, despite the increased toxicity expressed by a higher rise of total bilirubin. Our review findings should be considered with caution because of the methodological weaknesses in the included trials, resulting in low- to very low-certainty evidence. Data on serious adverse events and health-related quality of life are lacking. We are also very much uncertain in the results of the reported non-serious adverse events. High-quality trials are needed to assess further the role of TACE followed by 3-DCRT for unresectable hepatocellular carcinoma.",
        "gold": "The review authors searched the medical literature in order to clarify the role of the combination of TACE followed by 3-DCRT for the treatment of primary hepatocellular carcinoma, and to compare their benefits and harms with TACE alone. We collected and analysed data from randomised clinical trials (clinical studies where people are randomly put into one of two or more treatment groups) of people with primary hepatocellular carcinoma who were able to receive TACE or 3-DCRT. Evidence is current to May 2018. The review included eight trials with 632 participants. All trials were at high risk of bias. TACE followed by 3-DCRT appeared to be superior to TACE in improving death from any cause and tumour response, despite an increased toxicity expressed by a higher rise of total bilirubin (measured by a blood test to see how well the liver is working). No trials reported serious side effects. One trial reported health-related quality of life (a measure of a person's satisfaction with their life and health), but this was ill-defined. The review findings were uncertain because the included trials had methodological weaknesses. More high-quality randomised clinical trials are needed to confirm or complete the review findings."
    },
    {
        "index": "cochrane-simplification-test-417",
        "sentence": "No eligible trials were identified. Fourteen studies that appeared to be relevant were excluded, as no study directly compared increased versus standard energy intakes in infants with CLD/BPD. However, two excluded trials provided some insights into the topic. One study showed that infants with CLD/BPD who were fed formula enriched with protein and minerals had improved growth parameters up until the cessation of the intervention at three months of corrected age. The other study compared different energy density of formula but identical energy intake by setting different feed volumes for both groups. It showed that both groups were unable to achieve the pre-designated feed volumes and that there were no differences in growth, respiratory outcomes, oedema and the diuretic requirements. To date, no randomised controlled trials are available that examine the effects of increased versus standard energy intake for preterm infants with (or developing) CLD/BPD. Research should be directed at evaluating the effects of various levels of energy intake on this group of infants on clinically important outcomes like mortality, respiratory status, growth and neurodevelopment. The benefits and harms of various ways of increasing energy intake, including higher energy density of milk feed and/or fluid volume (clinically realistic target volume should be set), parenteral nutrition, and the use of various constituents of energy like carbohydrate, protein and fat for this purpose also need to be assessed.",
        "gold": "Studies have shown that these babies have higher energy expenditure and lower energy intake compared with babies without CLD/BPD. Increasing energy intake for these babies beyond standard levels may therefore seem beneficial. However, setting high targets for energy intake for these babies may not be achievable. Furthermore, methods of increasing energy intake such as increasing the milk volume or concentration or giving intravenous nutrition may lead to complications of their own. We planned to examine whether increasing energy intake for these babies improves their breathing status, their growth and development, and reduces their risk of death without producing significant complications. Having found no suitable study to date that answers these questions, we are currently unable to provide any evidence on whether increasing the energy intake for babies with (or developing) CLD/BPD is overall beneficial."
    },
    {
        "index": "cochrane-simplification-test-418",
        "sentence": "Altogether 13 studies enrolling 2341 participants (and involving 2360 procedures) fulfilled the inclusion criteria. The quality of evidence was very low (subclavian vein N = 3) or low (subclavian vein N = 4, femoral vein N = 2) for most outcomes, moderate for one outcome (femoral vein) and high at best for two outcomes (subclavian vein N = 1, femoral vein N = 1). Most of the trials had unclear risk of bias across the six domains, and heterogeneity among the studies was significant. For the subclavian vein (nine studies, 2030 participants, 2049 procedures), two-dimensional ultrasound reduced the risk of inadvertent arterial puncture (three trials, 498 participants, risk ratio (RR) 0.21, 95% confidence interval (CI) 0.06 to 0.82; P value 0.02, I\u00b2 = 0%) and haematoma formation (three trials, 498 participants, RR 0.26, 95% CI 0.09 to 0.76; P value 0.01, I\u00b2 = 0%). No evidence was found of a difference in total or other complications (together, US, USD), overall (together, US, USD), number of attempts until success (US) or first-time (US) success rates or time taken to insert the catheter (US). For the femoral vein, fewer data were available for analysis (four studies, 311 participants, 311 procedures). No evidence was found of a difference in inadvertent arterial puncture or other complications. However, success on the first attempt was more likely with ultrasound (three trials, 224 participants, RR 1.73, 95% CI 1.34 to 2.22; P value < 0.0001, I\u00b2 = 31%), and a small increase in the overall success rate was noted (RR 1.11, 95% CI 1.00 to 1.23; P value 0.06, I\u00b2 = 50%). No data on mortality or participant-reported outcomes were provided. On the basis of available data, we conclude that two-dimensional ultrasound offers small gains in safety and quality when compared with an anatomical landmark technique for subclavian (arterial puncture, haematoma formation) or femoral vein (success on the first attempt) cannulation for central vein catheterization. Data on insertion by inexperienced or experienced users, or on patients at high risk for complications, are lacking. The results for Doppler ultrasound techniques versus anatomical landmark techniques are uncertain.",
        "gold": "This Cochrane systematic review compared landmark techniques versus ultrasound guidance. The evidence is current to\u00b4January 2013. We included in the review 13 studies enrolling 2341 participants (and involving 2360 procedures). The studies were varied, and their quality was not high. We reran the search in August 2014. We will deal with any studies of interest when we update the review. Nevertheless, ultrasound offered some benefits, as it reduced the risk of arterial puncture and severe bruising in subclavian vein catheterization. Fewer data were available for femoral vein catheterization, but success rates seemed to be higher with ultrasound. No evidence showed a significant difference in complication rates or in time taken to cannulate at either site. On the basis of available data, we conclude that two-dimensional ultrasound offers small advantages in safety and quality when compared with an anatomical landmark technique for subclavian vein (reduced arterial puncture and haematoma formation) or femoral vein (reduced success on the first attempt) cannulation for central vein catheterization, but these findings do not necessarily hold for all groups of ultrasound users or for patients at high risk for complications. The results for Doppler ultrasound techniques versus anatomical landmark techniques are uncertain."
    },
    {
        "index": "cochrane-simplification-test-419",
        "sentence": "Fifteen studies were included using four different methods of administration of physostigmine. Four studies, 29 people, used intravenous infusion; seven, 131 people, used a conventional oral form; four, 1456 people, used a controlled-release oral form, and one study of 181 people used a verum skin patch. Intravenous infusion  There are no usable results from the intravenous infusion trials, Oral form  The few results from the trials of the conventional oral form showed no benefit of physostigmine compared with placebo.   Controlled release  The results from two of the four studies of the controlled-release physostigmine apply only to a group of patients identified as responders in a pre-randomization titration period. The best dose physostigmine was associated with improvement on the ADAS-Cog score compared with placebo at 6, 12 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial (22/183 vs 2/183)(OR 5.92, 95% confidence limits 2.59 to 13.54, p<0.0001) and suffering at least one event of nausea, vomiting, diarrhoea, anorexia, dizziness, stomach pain, flatulence or sweating compared with placebo at 6 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial due to adverse events (13/83 vs 5/93)(OR 3.05, 95% CI 1.15 to 8.07, p=0.02) and suffering at least one event of nausea, vomiting, diarrhoea, anorexia, dizziness, stomach pain, tremor, asthenia or sweating compared with placebo at 12 weeks. When no attempt was made to identify responders and all relevant patients with Alzheimer's disease were randomized, fixed dose physostigmine (mean 33 mg/day) was associated with a statistically significantly higher number withdrawing (234/358 vs 31/117)(OR 4.82, 95% CI 3.17 to 7.33, p<0.00001), withdrawing due to adverse events (196/358 vs 10/117) (OR 6.54, 95%CI 4.29 to 9.95, p<0.00001) and suffering at least one event of nausea, vomiting, diarrhoea, anorexia, dizziness, stomach pain, dyspepsia, sweating, asthenia, dyspnoea or abnormal dreaming, but with no benefit on cognition compared with placebo at 24 weeks. Verum patch  The double dose (delivering mean dose 12 mg/day) was associated with statistically significantly higher numbers suffering at least one adverse event of vomiting, nausea, or abdominal cramps, and the lower dose (delivering mean dose 5.7mg/day) was associated with statistically significantly higher numbers suffering gastrointestinal complaints compared with placebo at 24 weeks. There was no difference between physostigmine (higher and lower dose) and placebo for numbers improved (CGIC) at 24 weeks. The evidence of effectiveness of physostigmine for the symptomatic treatment of Alzheimer's disease is limited. Even in a controlled release formulation designed to overcome the short half-life, physostigmine showed no convincing benefit and adverse effects remained common leading to a high rate of withdrawal.",
        "gold": "Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia. Investigation of this property has been limited by the very short half-life of physostigmine. Various forms of administering the drug have been tried to overcome this problem, most recently a controlled-release (CR) oral formulation, and a skin patch. An additional limiting factor has been a high incidence of adverse effects, including nausea, vomiting and diarrhoea. Physostigmine appears to have no advantage over some newer anticholinesterase drugs. The short half-life remains a serious disadvantage and requires complex forms of administration. There is no reason to recommend further research into this drug."
    },
    {
        "index": "cochrane-simplification-test-420",
        "sentence": "We included 13 trials involving a total of 16,112 participants. Eleven trials recruited participants with history of coronary heart disease, two trials recruited participants with history of stroke, and one trial recruited participants with a mix of people with CVD. We judged overall risk of bias to be moderate. The meta-analysis (including all fibrate trials) showed evidence for a protective effect of fibrates primarily compared to placebo for the primary composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI), and vascular death (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.94; participants = 16,064; studies = 12; I2 = 45%, fixed effect). Fibrates were moderately effective for preventing MI occurrence (RR 0.86, 95% CI 0.80 to 0.93; participants = 13,942; studies = 10; I2 = 24%, fixed effect). Fibrates were not effective against all-cause mortality (RR 0.98, 95% CI 0.91 to 1.06; participants = 13,653; studies = 10; I2 = 23%), death from vascular causes (RR 0.95, 95% CI 0.86 to 1.05; participants = 13,653; studies = 10; I2 = 11%, fixed effect), and stroke events (RR 1.03, 95% CI 0.91 to 1.16; participants = 11,719; studies = 6; I2 = 11%, fixed effect). Excluding clofibrate trials, as the use of clofibrate was discontinued in 2002 due to safety concerns, the remaining class of fibrates were no longer effective in preventing the primary composite outcome (RR 0.90, 95% CI 0.79 to 1.03; participants = 10,320; studies = 7; I2 = 50%, random effects). However, without clofibrate data, fibrates remained effective in preventing MI (RR 0.85, 95% CI 0.76 to 0.94; participants = 8304; studies = 6; I2 = 47%, fixed effect). There was no increase in adverse events with fibrates compared to control. Subgroup analyses showed the benefit of fibrates on the primary composite outcome to be consistent irrespective of age, gender, and diabetes mellitus. Moderate evidence showed that the fibrate class can be effective in the secondary prevention of composite outcome of non-fatal stroke, non-fatal MI, and vascular death. However, this beneficial effect relies on the inclusion of clofibrate data, a drug that was discontinued in 2002 due to its unacceptably large adverse effects. Further trials of the use of fibrates in populations with previous stroke and also against a background treatment with statins (standard of care) are required.",
        "gold": "The duration of fibrates ranged from 12 months to 8 years. We included 13 trials in this review with a total of 16,112 participants with a history of coronary heart disease or stroke. This review includes evidence identified up to October 2014. Our analysis showed that when compared primarily to placebo, fibrates can be effective for prevention of composite outcome of non-fatal stroke, non-fatal heart attack (myocardial infarction), and death due to circulatory disease. However, this beneficial effect relies on the inclusion on data from clofibrates, a drug that was discontinued in 2002 because of safety concerns. In other words, there is no good evidence to support the use of currently available fibrates in the prevention of future heart attacks, strokes, and circulatory disease death in people with existing circulatory disease. In combination with clofibrate data, quality of evidence was moderate for the composite (non-fatal stroke, non-fatal myocardial infarction (MI), and vascular death) and MI (non-fatal or fatal) outcomes and low for stroke (ischaemic or haemorrhagic, non-fatal or fatal) and death from vascular or any cause during the treatment and scheduled follow-up period. The quality of evidence without clofibrate data was moderate for MI (non-fatal or fatal) outcome and low for the composite (non-fatal stroke, non-fatal MI, and vascular death), stroke (ischaemic or haemorrhagic, non-fatal or fatal), and death from vascular or any cause outcomes during the treatment and scheduled follow-up period."
    },
    {
        "index": "cochrane-simplification-test-421",
        "sentence": "Twelve trials involving 3285 healthy women at low risk of excessive bleeding undergoing elective CS (nine trials, 2453 participants) or spontaneous birth (three trials, 832 participants) satisfied inclusion criteria and contributed data to the analysis. All participants received routine prophylactic uterotonics in accordance with the local guideline in addition to TA or placebo or no intervention. Overall, included studies had moderate risk of bias for random sequence generation, allocation concealment, blinding, selective reporting and low risk of bias for incomplete data. The quality of evidence was also as assessed using GRADE. Blood loss greater than 400 mL or 500 mL, and more than 1000 mL was less common in women who received TA versus placebo or no intervention (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.42 to 0.63, six trials, 1398 women; moderate quality evidence) and (RR 0.40, 95% CI 0.23 to 0.71, six trials, 2093 women; moderate quality evidence), respectively. TA was effective in decreasing the incidence of blood loss greater than 1000 mL in women who had undergone CS (RR 0.43, 95% CI 0.23, 0.78, four trials, 1534 women), but not vaginal birth (RR 0.28, 95% CI 0.06, 1.36, two trials 559 women). The effect of TA on blood loss greater than 500 mL or 400 mL was more pronounced in the group of women having vaginal birth than in women who had CS. Mean blood loss (from delivery until two hours postpartum) was lower in women who received TA versus placebo or no intervention (mean difference MD - 77.79 mL, 95% CI -97.95, -57.64, five trials, 1186 women) and this effect was similar following vaginal birth and CS. Additional medical interventions (moderate quality evidence) and blood transfusions were less frequent in women receiving TA versus placebo or no interventions. Mild side effects such as nausea, vomiting, dizziness were more common with the use of TA (moderate quality evidence). The effect of TA on maternal mortality, severe morbidity and thromboembolic events is uncertain (low quality evidence). TA (in addition to uterotonic medications) decreases postpartum blood loss and prevents PPH and blood transfusions following vaginal birth and CS in women at low risk of PPH based on studies of mixed quality. There is insufficient evidence to draw conclusions about serious side effects, but there is an increase in the incidence of minor side effects with the use of TA. Effects of TA on thromboembolic events and mortality as well as its use in high-risk women should be investigated further.",
        "gold": "TA decreased blood loss greater than 400 mL or greater than 500 mL and this effect was more apparent with vaginal births. The studies had methodological shortcomings. Blood loss greater than 1000 mL decreased with the use of TA in six trials (2093 women), however, the difference was most obvious in caesarean section (two trials, 1400 women) and not in vaginal birth in which there were few such outcomes (one trial, 439 women). Mean blood loss decreased with the use of TA by 77 mL, overall (five studies, 1186 women) and with both vaginal and caesarean section births. This finding was based on studies with methodological limitations. The studies were too small to detect the effect of TA on maternal death or blood clots. Mild side effects, which include diarrhoea, nausea and vomiting, were more common in women who received TA versus placebo or no intervention. No differences in blood loss and side effects were found when two different doses of TA were evaluated. Further larger studies are needed to investigate the effects of TA on maternal deaths and formation of clots in the blood (thromboembolism)."
    },
    {
        "index": "cochrane-simplification-test-422",
        "sentence": "We identified 12 studies (2494 participants: 1586 children and 908 elderly) comparing amantadine and rimantadine with placebo, paracetamol (one trial: 69 children) or zanamivir (two trials: 545 elderly) to treat influenza A. Amantadine was effective in preventing influenza A in children (773 participants, risk ratio (RR) 0.11; 95% confidence interval (CI) 0.04 to 0.30). The assumed risk of influenza A in the control group was 10 per 100. The corresponding risk in the rimantadine group was one per 100 (95% CI 0 to 3). Nevertheless, the quality of the evidence was low and the safety of the drug was not well established. For treatment, rimantadine was beneficial in abating fever on day three of treatment in children: one selected study with low risk of bias, moderate evidence quality and 69 participants (RR 0.36; 95% CI 0.14 to 0.91). The assumed risk was 38 per 100. The corresponding risk in the rimantadine group was 14 per 100 (95% CI 5 to 34). Rimantadine did not show any prophylactic effect in the elderly. The quality of evidence was very low: 103 participants (RR 0.45; 95% CI 0.14 to 1.41). The assumed risk was 17 per 100. The corresponding risk in the rimantadine group was 7 per 100 (95% CI 2 to 23). There was no evidence of adverse effects caused by treatment with amantadine or rimantadine. We found no studies assessing amantadine in the elderly. The quality of the evidence combined with a lack of knowledge about the safety of amantadine and the limited benefits of rimantadine, do not indicate that amantadine and rimantadine compared to control (placebo or paracetamol) could be useful in preventing, treating and shortening the duration of influenza A in children and the elderly.",
        "gold": "We identified 12 trials (2494 participants: 1586 children and 908 elderly). We looked for trials that compared amantadine or rimantadine with no intervention, placebos or control drugs in children and the elderly. The most recent searches were completed in October 2014. We looked at several outcomes, including influenza A, fever duration, cough, headache, nausea/vomiting, dizziness and stimulation/insomnia. Although amantadine was effective in preventing influenza A in children, it would be necessary to use it in up to 17 children over a period of 14 to 18 weeks to prevent one case of influenza A. Furthermore, the safety of the drug was not well established. The quality of the evidence was low. The effectiveness of both antivirals was limited to a benefit from rimantadine in the reduction of fever by day three of treatment in children. The quality of the evidence was moderate. This benefit does not seem to justify a recommendation for using rimantadine to treat all children with influenza A. Rimantadine did not show a prophylactic (preventative) effect in the elderly. The quality of evidence was very low. The quality of the evidence combined with a lack of knowledge about the safety of amantadine and the limited benefits of rimantadine, do not indicate that amantadine and rimantadine compared to control (placebo or paracetamol) could be useful in preventing, treating and shortening the duration of influenza A in children and the elderly."
    },
    {
        "index": "cochrane-simplification-test-423",
        "sentence": "Nine trials, which included a total of 1512 women, met the inclusion criteria of this Cochrane review. Most of these studies included women with unexplained infertility. In seven studies the women were undergoing IUI and in two studies the women were trying to conceive from sexual intercourse. Eight trials compared intentional endometrial injury with no injury/placebo procedure; of these two trials also compared intentional endometrial injury in the cycle prior to IUI with intentional endometrial injury in the IUI cycle. One trial compared higher vs. lower degree of intentional endometrial injury. Intentional endometrial injury vs. either no intervention or a sham procedure We are uncertain whether endometrial injury improves live birth/ongoing pregnancy as the quality of the evidence has been assessed as very low (risk ratio (RR) 2.22, 95% confidence interval (CI) 1.56 to 3.15; six RCTs, 950 participants; I\u00b2 statistic = 0%, very low quality evidence). When we restricted the analysis to only studies at low risk of bias the effect was imprecise and the evidence remained of very low quality (RR 2.64, 95% CI 1.03 to 6.82; one RCT, 105 participants; very low quality evidence). Endometrial injury may improve clinical pregnancy rates however the evidence is of low quality (RR 1.98, 95% CI 1.51 to 2.58; eight RCTs, 1180 participants; I\u00b2 statistic = 0%, low quality evidence). The average pain experienced by participants undergoing endometrial injury was 6/10 on a zero-10 visual analogue scale (VAS)(standard deviation = 1.5). However, only one study reported this outcome. Higher vs. lower degree of intentional endometrial injury When we compared hysteroscopy with endometrial injury to hysteroscopy alone, there was no evidence of a difference in ongoing pregnancy rate (RR 1.29, 95% CI 0.71 to 2.35; one RCT, 332 participants; low quality evidence) or clinical pregnancy rate (RR 1.15, 95% CI 0.66 to 2.01; one RCT, 332 participants, low quality evidence). This study did not report the primary outcome of pain during the procedure. Timing of intentional endometrial injury When endometrial injury was performed in the cycle prior to IUI compared to the same cycle as the IUI, there was no evidence of a difference in ongoing pregnancy rate (RR 0.65, 95% CI 0.37 to 1.16, one RCT, 176 participants; very low quality evidence) or clinical pregnancy rate (RR 0.82, 95% CI 0.50 to 1.36; two RCTs, 276 participants; very low quality evidence). Neither of these studies reported the primary outcome of pain during the procedure. In all three comparisons there was no evidence of an effect on miscarriage, ectopic pregnancy or multiple pregnancy. No studies reported bleeding secondary to the procedure. It is uncertain whether endometrial injury improves the probability of pregnancy and live birth/ongoing pregnancy in women undergoing IUI or attempting to conceive via sexual intercourse. The pooled results should be interpreted with caution as we graded the quality of the evidence as either low or very low. The main reasons we downgraded the quality of the evidence were most included studies were at a high risk of bias and had an overall low level of precision. Further well-conducted RCTs that recruit large numbers of participants and minimise internal bias are required to confirm or refute these findings.",
        "gold": "Nine randomised controlled trials met the inclusion criteria of this review, and included a total of 1512 women. The women in seven studies were trying to get pregnant from IUI, and from intercourse in two studies. Most women had a type of subfertility known as unexplained subfertility, which means that after having all routine tests done there is no obvious explanation for why the couple has not become pregnant so far. Eight trials compared intentional endometrial injury with no injury/placebo procedure; of these two trials also compared intentional endometrial injury in the cycle prior to IUI with intentional endometrial injury in the IUI cycle. One trial compared higher vs. lower degree of intentional endometrial injury. The evidence is current to 31 October 2015. The results from the included studies suggest a beneficial effect of endometrial injury on the chance of getting pregnant, but the studies are associated with many significant limitations. Therefore, it is not possible to say with any confidence whether endometrial injury can increase the probability of pregnancy. We are uncertain whether endometrial injury increases the probability of a live birth or a pregnancy beyond 12 weeks. The endometrial injury procedure is a common procedure and is known to cause a degree of temporary pain or discomfort. Only one included study reported on whether the women experienced pain during the procedure, and the average pain experienced was six out of 10 on a visual scale from zero to 10. Endometrial injury does not seem to have an effect on miscarriage, ectopic pregnancy or multiple pregnancy. No studies reported bleeding after the procedure. The quality of the evidence was low or very low as assessed using GRADE criteria. In general, the studies included in this review were not very well designed and did not recruit a high enough number of women to provide meaningful results. This means the results must be treated cautiously, and further studies are needed to confirm the findings. There remains uncertainty about whether or not the endometrial injury procedure increases the probability of having a baby."
    },
    {
        "index": "cochrane-simplification-test-424",
        "sentence": "We included four RCTs (3905 participants), all of which were at high risk of bias. The studies all evaluated one comparison: professional oral care versus usual oral care. We did not pool the results from one study (N = 834 participants), which was stopped at interim analysis due to lack of a clear difference between groups. We were unable to determine whether professional oral care resulted in a lower incidence rate of NHAP compared with usual oral care over an 18-month period (hazard ratio 0.65, 95% CI 0.29 to 1.46; one study, 2513 participants analysed; low-quality evidence). We were also unable to determine whether professional oral care resulted in a lower number of first episodes of pneumonia compared with usual care over a 24-month period (RR 0.61, 95% CI 0.37 to 1.01; one study, 366 participants analysed; low-quality evidence). There was low-quality evidence from two studies that professional oral care may reduce the risk of pneumonia-associated mortality compared with usual oral care at 24-month follow-up (RR 0.41, 95% CI 0.24 to 0.72, 507 participants analysed). We were uncertain whether or not professional oral care may reduce all-cause mortality compared to usual care, when measured at 24-month follow-up (RR 0.55, 95% CI 0.27 to 1.15; one study, 141 participants analysed; very low-quality evidence). Only one study (834 participants randomised) measured adverse effects of the interventions. The study identified no serious events and 64 non-serious events, the most common of which were oral cavity disturbances (not defined) and dental staining. No studies evaluated oral care versus no oral care. Although low-quality evidence suggests that professional oral care could reduce mortality due to pneumonia in nursing home residents when compared to usual care, this finding must be considered with caution. Evidence for other outcomes is inconclusive. We found no high-quality evidence to determine which oral care measures are most effective for reducing nursing home-acquired pneumonia. Further trials are needed to draw reliable conclusions.",
        "gold": "This review was carried out through Cochrane Oral Health. We searched scientific databases for relevant studies, up to 15 November 2017. We included four studies, with a total of 3905 participants randomly assigned to treatment or usual care. Participants were long-term-care elderly residents in nursing homes who did not have pneumonia at the beginning of the studies. Some of the participants had dementia or systemic diseases. All studies focused on the comparison between 'professional' mouth care and 'usual' mouth care. None of the studies evaluated oral care versus no oral care. We identified four studies, all of which compared professional mouth care to usual mouth care in nursing home residents. From the limited evidence, we could not tell whether professional oral mouth care was better or worse than usual mouth care for preventing pneumonia. The evidence for death from any cause was inconclusive, but the studies did suggest that professional mouth care may reduce the number of deaths caused by pneumonia, compared to usual mouth care, when measured after 24 months. Only one study measured negative effects of the interventions, and reported that there were no serious events. The most common non-serious events reported were damage to the mouth and tooth staining. The quality of the evidence is low or very low, because of the small number of studies and problems with their design. Therefore, we cannot rely on the findings, and further research is required."
    },
    {
        "index": "cochrane-simplification-test-425",
        "sentence": "Five RCTs (149 participants) met the inclusion criteria. These studies assessed bismuth subsalicylate versus placebo, budesonide versus placebo, mesalazine versus mesalazine plus cholestyramine and beclometasone dipropionate versus mesalazine. The study which assessed mesalazine versus mesalazine plus cholestyramine and the study which assessed beclometasone dipropionate versus mesalazine were judged to be at high risk of bias due to lack of blinding. The study which compared bismuth subsalicylate versus us placebo was judged as low quality due to a very small sample size and limited data. The other 3 studies were judged to be at low risk of bias. Budesonide (9 mg/day for 6 to 8 weeks) was significantly more effective than placebo for induction of clinical and histological response. Clinical response was noted in 88% of budesonide patients compared to 38% of placebo patients (2 studies; 57 participants; RR 2.03, 95% CI 1.25 to 3.33; GRADE = low). Histological response was noted in 78% of budesonide patients compared to 33% of placebo patients (2 studies; 39 patients; RR 2.44, 95% CI 1.13 to 5.28; GRADE = low). Forty-one patients were enrolled in the study assessing mesalazine (2.4 g/day) versus mesalazine plus cholestyramine (4 g/day). Clinical response was noted in 85% of patients in the mesalazine group compared to 86% of patients in the mesalazine plus cholestyramine group (RR 0.99, 95% CI 0.77 to 1.28; GRADE = low). Five patients were enrolled in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks versus placebo). There were no differences in clinical (P=0.10) or histological responses (P=0.71) in patients treated with bismuth subsalicylate compared with placebo (GRADE = very low). Forty-six patients were enrolled in the trial studying beclometasone dipropionate (5 mg/day or 10 mg/day) versus mesalazine (2.4 g/day). There were no differences in clinical remission at 8 weeks (RR 0.97; 95% CI 0.75 to 1.24; GRADE = low) and 12 months of treatment (RR 1.29; 95% CI 0.40 to 4.18; GRADE = very low). Although patients receiving beclometasone dipropionate (84%) and mesalazine (86%) achieved clinical remission at 8 weeks, it was not maintained at 12 months (26% and 20%, respectively). Adverse events reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, hyperhidrosis and headache. Nausea and skin rash were reported as adverse events in the mesalazine study. Adverse events in the beclometasone dipropionate trial include nausea, sleepiness and change of mood. No adverse events were reported in the bismuth subsalicylate study. Low quality evidence suggests that budesonide may be effective for the treatment of active lymphocytic colitis. This benefit needs to be confirmed by a large placebo -controlled trial. Low quality evidence also suggests that mesalazine with or without cholestyramine and beclometasone dipropionate may be effective for the treatment of lymphocytic colitis, however this needs to be confirmed by large placebo-controlled studies. No conclusions can be made regarding bismuth subsalicylate due to the very small number of patients in the study, Further trials studying interventions for lymphocytic colitis are warranted.",
        "gold": "Five studies including 149 participants were identified. These studies assessed budesonide versus placebo (e.g. a sugar pill), mesalazine versus mesalazine plus cholestyramine and beclometasone dipropionate versus mesalazine and Pepto-Bismol\u00ae versus placebo. The study which compared mesalazine to mesalazine plus cholestyramine and the study which compared beclometasone dipropionate to mesalazine were judged to be of low quality. The study which compared Pepto-Bismol\u00ae bismuth subsalicylate to a placebo was judged as low quality due to a very small sample size (5 participants) and limited data. The other three studies were judged to be high quality. A pooled analysis of two studies (57 participants) showed that budesonide (9 mg/day for 6 to 8 weeks) was superior to placebo for improvement of diarrhea and improvement of microscopic inflammation of the bowel. Improvement in diarrhea was noted in 88% of budesonide participants compared to 38% of placebo participants. Improvement in microscopic inflammation was reported in 78% of budesonide participants compared to 33% of placebo participants. Forty-one participants were enrolled in the study that compared mesalazine (2.4. g/day) to mesalazine plus cholestyramine (4 g/day). Improvement in diarrhea was noted in 85% of participants in the mesalazine group compared to 86% of participants in the mesalazine plus cholestyramine group. Five patients were enrolled in the trial studying Pepto-Bismol\u00ae (nine 262 mg tablets daily for 8 weeks versus placebo). There were no differences in improvement of diarrhea or in improvement of microscopic inflammation of the bowel. Forty-six participants were enrolled in the trial studying beclometasone dipropionate (5 mg/day or 10 mg/day) versus mesalazine (2.4 g/day). Although participants receiving beclometasone dipropionate (84%) and mesalazine (86%) had improved diarrhea at 8 weeks, this improvement was not maintained at 12 months (26% and 20%, respectively). Side effects reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, excessive sweating and headache. Side effects reported in the mesalazine plus cholestyramine study included nausea and skin rash. Side effects in the beclometasone dipropionate trial included nausea, sleepiness and change of mood. No side effects were reported in the Pepto-Bismol\u00ae study. Low quality evidence suggests that budesonide may be an effective therapy for the treatment of lymphocytic colitis. Low quality evidence also suggests that mesalazine with or without cholestyramine and beclometasone dipropionate may be effective for treatment of lymphocytic colitis. No conclusions can be made regarding bismuth subsalicylate due to the very small number of participants in the study. In the future, researchers should consider further large placebo-controlled trials of budesonide to confirm the suggested benefit and safety of this therapy. Bismuth subsalicylate, which has less potential for toxicity than budesonide, also warrants further study. The effectiveness and safety of mesalazine with or without cholestyramine, and beclometasone dipropionate need to be investigated in a large placebo-controlled studies."
    },
    {
        "index": "cochrane-simplification-test-426",
        "sentence": "Twelve randomised controlled trials were included and evaluated outcomes in 3259 randomised patients. Intervention duration ranged from 6 months (26 weeks) to 12 months (52 weeks). Nine trials compared SMBG with usual care without monitoring, one study compared SMBG with SMUG, one study was a three-armed trial comparing SMBG and SMUG with usual care and one study was a three-armed trial comparing less intensive SMBG and more intensive SMBG with a control group. Seven out of 11 studies had a low risk of bias for most indicators. Meta-analysis of studies including patients with a diabetes duration of one year or more showed a statistically significant SMBG induced decrease in HbA1c at up to six months follow-up (-0.3; 95% confidence interval (CI) -0.4 to -0.1; 2324 participants, nine trials), yet an overall statistically non-significant SMBG induced decrease was seen at 12 month follow-up (-0.1; 95% CI -0.3 to 0.04; 493 participants, two trials). Qualitative analysis of the effect of SMBG on well-being and quality of life showed no effect on patient satisfaction, general well-being or general health-related quality of life. Two trials reported costs of self-monitoring: One trial compared the costs of self-monitoring of blood glucose with self-monitoring of urine glucose based on nine measurements per week and with the prices in US dollars for self-monitoring in 1990. Authors concluded that total costs in the first year of self-monitoring of blood glucose, with the purchase of a reflectance meter were 12 times more expensive than self-monitoring of urine glucose ($481 or 361 EURO [11/2011 conversion] versus $40 or 30 EURO [11/2011 conversion]). Another trial reported a full economical evaluation of the costs and effects of self-monitoring. At the end of the trial, costs for the intervention were \u00a389 (104 EURO [11/2011 conversion]) for standardized usual care (control group), \u00a3181 (212 EURO [11/2011 conversion]) for the less intensive self-monitoring group and \u00a3173 (203 EURO [11/2011 conversion]) for the more intensive self-monitoring group. Higher losses to follow-up in the more intensive self-monitoring group were responsible for the difference in costs, compared to the less intensive self-monitoring group. There were few data on the effects on other outcomes and these effects were not statistically significant. None of the studies reported data on morbidity. From this review, we conclude that when diabetes duration is over one year, the overall effect of self-monitoring of blood glucose on glycaemic control in patients with type 2 diabetes who are not using insulin is small up to six months after initiation and subsides after 12 months. Furthermore, based on a best-evidence synthesis, there is no evidence that SMBG affects patient satisfaction, general well-being or general health-related quality of life. More research is needed to explore the psychological impact of SMBG and its impact on diabetes specific quality of life and well-being, as well as the impact of SMBG on hypoglycaemia and diabetic complications.",
        "gold": "Two studies reported costs of self-monitoring: One study compared the costs of self-monitoring of blood glucose with self-monitoring of urine glucose based on nine measurements per week and with the prices in US dollars for self-monitoring in 1990. They concluded that total costs in the first year of self-monitoring of blood glucose, with the purchase of a reflectance meter were 12 times more expensive than self-monitoring of urine glucose ($481 or 361 EURO [11/2011 conversion] versus $40 or 30 EURO [11/2011 conversion]). Another study reported a full economical evaluation of the costs and effects of self-monitoring. At the end of the trial, costs for the intervention were \u00a389 (104 EURO [11/2011 conversion]) for standardized usual care (control group), \u00a3181 (212 EURO [11/2011 conversion]) for the less intensive self-monitoring group and \u00a3173 (203 EURO [11/2011 conversion]) for the more intensive self-monitoring group. We did not find good evidence for an effect on general health-related quality of life, general well-being, patient satisfaction, or on the decrease of the number of hypoglycaemic episodes. However, hypoglycaemic episodes were more often reported in the self-monitoring blood glucose groups than in the control groups (four studies). Because patients in the self-monitoring blood glucose groups can use their device to confirm both periods of asymptomatic and symptomatic hypoglycaemic episodes, this is according to expectations."
    },
    {
        "index": "cochrane-simplification-test-427",
        "sentence": "Eleven studies involving 471 participants with AsPD met the inclusion criteria, although data were available from only five studies involving 276 participants with AsPD. Only two studies focused solely on an AsPD sample. Eleven different psychological interventions were examined. Only two studies reported on reconviction, and only one on aggression. Compared to the control condition, cognitive behaviour therapy (CBT) plus standard maintenance was superior for outpatients with cocaine dependence in one study, but CBT plus treatment as usual was not superior for male outpatients with recent verbal/physical violence in another. Contingency management plus standard maintenance was superior for drug misuse for outpatients with cocaine dependence in one study but not in another, possibly because of differences in the behavioural intervention. However, contingency management was superior in social functioning and counselling session attendance in the latter. A multi-component intervention utilising motivational interviewing principles, the \u2018Driving Whilst Intoxicated program\u2019, plus incarceration was superior to incarceration alone for imprisoned drink-driving offenders. Results suggest that there is insufficient trial evidence to justify using any psychological intervention for adults with\u00a0AsPD. Disappointingly few of the included studies addressed the primary outcomes defined in this review (aggression, reconviction, global functioning, social functioning, adverse effects). Three interventions (contingency management with standard maintenance; CBT with standard maintenance; 'Driving Whilst Intoxicated program' with incarceration) appeared effective, compared to the control condition, in terms of improvement in at least one outcome in at least one study. Each of these interventions had been originally developed for people with substance misuse problems. Significant improvements were mainly confined to outcomes related to substance misuse. No study reported significant change in any specific antisocial behaviour. Further research is urgently needed for this prevalent and costly condition.",
        "gold": "We considered 11 studies, but were unable to draw any firm conclusions from the evidence available. Although several studies looked at treatments to reduce drug or alcohol misuse in people with antisocial personality disorder, few studies focused on treating the disorder itself. Only three studies reported outcome measures that were originally defined in the review protocol as being of particular importance in this disorder (reconviction and aggression). Nonetheless, there was some evidence that a type of treatment known as contingency management (which provides rewards for progress in treatment) could help people with antisocial personality disorder to reduce their misuse of drugs or alcohol. Further research is urgently needed to clarify which psychological treatments are effective for people with this disorder. This research is best carried out using carefully designed clinical trials. Such trials should focus on the key features of antisocial personality disorder. To be informative, they need to be carried out with samples of participants of sufficient size."
    },
    {
        "index": "cochrane-simplification-test-428",
        "sentence": "This updated review included 11 studies. Six studies contributed to one or more analyses related to the common cold, with up to 1047 participants. Five studies contributed to one or more analyses relating to purulent rhinitis, with up to 791 participants. One study contributed only to data on adverse events and one met the inclusion criteria but reported only summary statistics without providing any numerical data that could be included in the meta-analyses. Interpretation of the combined data is limited because some studies included only children, or only adults, or only males; a wide range of antibiotics were used and outcomes were measured in different ways. There was a moderate risk of bias because of unreported methods details or because an unknown number of participants were likely to have chest or sinus infections. Participants receiving antibiotics for the common cold did no better in terms of lack of cure or persistence of symptoms than those on placebo (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.59 to 1.51, (random-effects)), based on a pooled analysis of six trials with a total of 1047 participants. The RR of adverse effects in the antibiotic group was 1.8, 95% CI 1.01 to 3.21, (random-effects). Adult participants had a significantly greater risk of adverse effects with antibiotics than with placebo (RR 2.62, 95% CI 1.32 to 5.18) (random-effects) while there was no greater risk in children (RR 0.91, 95% CI 0.51 to 1.63). The pooled RR for persisting acute purulent rhinitis with antibiotics compared to placebo was 0.73 (95% CI 0.47 to 1.13) (random-effects), based on four studies with 723 participants. There was an increase in adverse effects in the studies of antibiotics for acute purulent rhinitis (RR 1.46, 95% CI 1.10 to 1.94). There is no evidence of benefit from antibiotics for the common cold or for persisting acute purulent rhinitis in children or adults. There is evidence that antibiotics cause significant adverse effects in adults when given for the common cold and in all ages when given for acute purulent rhinitis. Routine use of antibiotics for these conditions is not recommended.",
        "gold": "To find out whether antibiotics work for the common cold we identified studies that compared one group of people taking an antibiotic with another group of people taking a medication that looked similar but contained no antibiotic (a placebo). We found six studies of the common cold, with 1047 participants and five studies of acute purulent rhinitis, with 791 participants. Many of the studies had flaws which might have biased the results, especially because many of the participants probably had chest or sinus infections that the researchers did not know about. Results suggest that antibiotics do not work for either the common cold or for acute purulent rhinitis and many people are affected by antibiotic side effects."
    },
    {
        "index": "cochrane-simplification-test-429",
        "sentence": "We included five trials (162 randomised participants); three were conducted in a hospital dermatology department. One study declared funding by a pharmaceutical company. Participants' ages ranged from 12 to 77 years; only two participants were younger than 15 years. Mean PASI score at baseline varied from 5.7 (i.e. mild) to 23 (i.e. severe) in four studies. Twenty-three of 162 participants had streptococcus-positive throat swab culture. We did not perform a meta-analysis due to heterogeneity of participants' characteristics and interventions. None of the trials measured our efficacy primary outcome, time-to-resolution, or the secondary outcome, risk of having at least one relapse at long-term follow-up. We rated the quality of the results as very low-quality evidence, due to high risk of bias (absence of blinding of participants and caregivers, and high risk of outcome reporting bias) and imprecision (single study data with a low number of events). Hence, we are very uncertain about the results presented. Guttate psoriasis One three-armed trial (N = 43) assessed penicillin (50,000 international units (IU)/kg/day in three doses) versus erythromycin (250 mg four times per day) versus no treatment (treatment for 14 days, with six-week follow-up from start of treatment). Adverse events and the proportion of participants achieving clear or almost clear skin were not measured. One trial (N = 20) assessed penicillin (1.6 MU (million units) intramuscularly once a day) versus no treatment (six weeks of treatment, with eight-week follow-up from start of treatment). At six-week (short-term) follow-up, no adverse events were observed in either group, and there was no statistically significant difference between the two groups in the proportion of participants with clear or almost clear skin (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.68 to 5.85). One trial (N = 20) assessed rifampicin (300 mg twice daily) versus placebo (14-day treatment duration; six-week follow-up from start of treatment); none of the review outcomes were measured. These trials did not measure the proportion of participants achieving PASI 75 or PGA 1 to 2. Chronic plaque psoriasis One trial (N = 50) assessed long-term azithromycin treatment (500 mg daily dose) versus vitamin C. Adverse events were reported in the azithromycin group (10 out of 30 had nausea and mild abdominal upset), but not in the vitamin C group. The proportion of participants who achieved clear or almost clear skin was not measured. In the azithromycin group, 18/30 versus 0/20 participants in the vitamin C group reached PASI 75 at the end of 48 weeks of treatment (RR 25.06, 95% CI 1.60 to 393.59). One trial (N = 29) assessed tonsillectomy versus no treatment, with 24-month follow-up after surgery. One participant in the tonsillectomy group had minor bleeding. At eight-week follow-up, 1/15 in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 90; and 3/15 participants in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 75 (RR 6.56, 95% CI 0.37 to 116.7). We found only five trials (N = 162), which assessed the effects of five comparisons (systemic antibiotic treatment (penicillin, azithromycin) or tonsillectomy). Two comparisons (erythromycin compared to no treatment, and rifampicin compared to placebo) did not measure any of the outcomes of interest. There was very low-quality evidence for the outcomes that were measured, Therefore, we are uncertain of both the efficacy and safety of antistreptococcal interventions for guttate and chronic plaque psoriasis. The included trials were at unclear or high risk of bias and involved only a small number of unrepresentative participants, with limited measurement of our outcomes of interest. The studies did not allow investigation into the influence of Streptococcal infection, and a key intervention (amoxicillin) was not assessed. Further trials assessing the efficacy and tolerance of penicillin V or amoxicillin are needed in children and young adults with guttate psoriasis.",
        "gold": "The evidence is current to January 2019. We included five studies (162 participants); three were conducted in hospital dermatology departments. Participants were 12 to 77 years old (100 males; 62 females). One study was funded by a pharmaceutical company. The severity of the condition ranged from mild to severe. Streptococcus bacteria were found in the throats of 14% of people. We classed outcomes measured within eight weeks of the start of treatment as short-term, and those measured at least one year after the start of treatment as long-term. The antibiotic trials in guttate psoriasis patients were all short-term in duration; the antibiotic trial in chronic plaque psoriasis was 48 weeks long. Three studies included participants with guttate psoriasis, and assessed the short-term effects of antibiotics: penicillin (20 participants), or erythromycin compared to no treatment (43 participants), and rifampicin compared to placebo (20 participants). Two studies included participants with chronic plaque psoriasis. One study assessed azithromycin (antibiotic) versus vitamin C at 48 weeks (50 participants); one assessed tonsillectomy versus no intervention at eight weeks and 24 months (29 participants). These results are backed by very low-quality evidence, so we are not certain of their accuracy. Each result is based on only one study. No studies measured our main outcome of interest, the time taken for the skin to be clear or almost clear of lesions, or the risk of relapsing at least once during long-term follow-up. No side effects were seen when penicillin was compared with no treatment in people with guttate psoriasis. Side effects were not measured for the comparisons of rifampicin versus placebo, or erythromycin versus no treatment. In participants with chronic plaque psoriasis, one trial assessed azithromycin versus vitamin C, and 10 participants in the azithromycin group complained of nausea or mild stomach upset. A trial of tonsillectomy versus no treatment reported one case of minor bleeding in the tonsillectomy group. Two studies in participants with chronic plaque psoriasis measured the number of participants achieving a 75% reduction on the Psoriasis Area and Severity Index (PASI 75). In one, 18/30 participants in the azithromycin group reached PASI 75 versus none in the vitamin C group. In the other, 3/15 in the tonsillectomy group reached PASI 75 versus none in the no treatment group. The guttate psoriasis trials did not assess this outcome. We are uncertain whether the number of participants with guttate psoriasis achieving clear or almost clear skin differs between those given penicillin and those receiving no treatment. Only one participant with chronic plaque psoriasis achieved almost clear skin in the tonsillectomy group compared to none in the no treatment group. The other three trials did not measure this outcome. Many of our main outcomes were not assessed. Those that were assessed were based on very low-quality evidence, meaning we are not sure of their accuracy. The studies were very small, and had a high risk of bias because participants and trial assessors were aware of treatment allocation. More studies are needed to see if antibiotic treatment of Streptococcal infection shortens the duration of acute guttate psoriasis, stopping it from turning into a long-term condition (chronic plaque psoriasis)."
    },
    {
        "index": "cochrane-simplification-test-430",
        "sentence": "We identified 12 RCTs enrolling 933 participants with MS; 464 were randomised to the vitamin D group, and 469 to the comparator group. Eleven trials tested vitamin D\u2083, and one trial tested vitamin D\u2082. Vitamin D\u2083 had no effect on the annualised relapse rate at 52 weeks' follow-up (rate difference -0.05, 95% CI -0.17 to 0.07; I\u00b2 = 38%; five trials; 417 participants; very low-quality evidence according to the GRADE instrument); on the Expanded Disability Status Scale at 52 weeks' follow-up (MD -0.25, 95% CI -0.61 to 0.10; I\u00b2 = 35%; five trials; 221 participants; very low-quality evidence according to GRADE); and on MRI gadolinium-enhancing T1 lesions at 52 weeks' follow-up (MD 0.02, 95% CI -0.45 to 0.48; I\u00b2 = 12%; two trials; 256 participants; very low-quality evidence according to GRADE). Vitamin D\u2083 did not increase the risk of serious adverse effects within a range of 26 to 52 weeks' follow-up (RD 0.01, 95% CI -0.03 to 0.04; I\u00b2 = 35%; eight trials; 621 participants; low-quality evidence according to GRADE) or minor adverse effects within a range of 26 to 96 weeks' follow-up (RD 0.02, 95% CI -0.02 to 0.06; I\u00b2 = 20%; eight trials; 701 participants; low-quality evidence according to GRADE). Three studies reported health-related quality of life (HRQOL) using different HRQOL scales. One study reported that vitamin D improved ratings on the psychological and social components of the HRQOL scale but had no effects on the physical components. The other two studies found no effect of vitamin D on HRQOL. Two studies reported fatigue using different scales. One study (158 participants) reported that vitamin D\u2083 reduced fatigue compared with placebo at 26 weeks' follow-up. The other study (71 participants) found no effect on fatigue at 96 weeks' follow-up. Seven studies reported on cytokine levels, four on T-lymphocyte proliferation, and one on matrix metalloproteinase levels, with no consistent pattern of change in these immunological outcomes. The randomised trials included in this review provided no data on time to first treated relapse, number of participants requiring hospitalisation owing to progression of the disease, proportion of participants who remained relapse-free, cognitive function, or psychological symptoms. To date, very low-quality evidence suggests no benefit of vitamin D for patient-important outcomes among people with MS. Vitamin D appears to have no effect on recurrence of relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), and MRI lesions. Effects on health-related quality of life and fatigue are unclear. Vitamin D\u2083 at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Seven ongoing studies will likely provide further evidence that can be included in a future update of this review.",
        "gold": "Our systematic search identified 12 studies enrolling 933 people with MS. Research shows that vitamin D has no effect on recurrence of relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), or new MRI gadolinium-enhancing T1 lesions. Its effects on health-related quality of life and fatigue are unclear. Our confidence in these results is very low because vitamin D has been evaluated in only a few small trials that we judged as having high risk of bias. Vitamin D supplementation appears to be safe for people with MS included in our review, but available data are limited. For people with MS, vitamin D supplementation appears to have no effect on relevant clinical outcomes or new MRI lesions. Vitamin D supplementation at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Seven trials are ongoing; they will likely provide further evidence for a future update of this review. This evidence is up-to-date as of October 2017."
    },
    {
        "index": "cochrane-simplification-test-431",
        "sentence": "We identified seven new studies in this update. We excluded six, and one study is ongoing so also not included in this update. This review contains a total of 62 included studies, with 4241 participants. Thirty-six studies used a cross-over design ranging from one to 15 days, with the greatest number (11) for seven days for each arm of the trial. Overall we judged the included studies to be at high risk of bias because the methods of randomisation and allocation concealment were poorly reported. The primary outcomes for this review were participant-reported pain and pain relief. Fifteen studies compared oral morphine modified release (Mm/r) preparations with morphine immediate release (MIR). Fourteen studies compared Mm/r in different strengths; six of these included 24-hour modified release products. Fifteen studies compared Mm/r with other opioids. Six studies compared MIR with other opioids. Two studies compared oral Mm/r with rectal Mm/r. Three studies compared MIR with MIR by a different route of administration. Two studies compared Mm/r with Mm/r at different times and two compared MIR with MIR given at a different time. One study was found comparing each of the following: Mm/r tablet with Mm/r suspension; Mm/r with non-opioids; MIR with non-opioids; and oral morphine with epidural morphine. In the previous update, a standard of 'no worse than mild pain' was set, equivalent to a score of 30/100 mm or less on a visual analogue pain intensity scale (VAS), or the equivalent in other pain scales. Eighteen studies achieved this level of pain relief on average, and no study reported that good levels of pain relief were not attained. Where results were reported for individual participants in 17 studies, 'no worse than mild pain' was achieved by 96% of participants (362/377), and an outcome equivalent to treatment success in 63% (400/638). Morphine is an effective analgesic for cancer pain. Pain relief did not differ between Mm/r and MIR. Modified release versions of morphine were effective for 12- or 24-hour dosing depending on the formulation. Daily doses in studies ranged from 25 mg to 2000 mg with an average of between 100 mg and 250 mg. Dose titration was undertaken with both instant release and modified release products. A small number of participants did not achieve adequate analgesia with morphine. Adverse events were common, predictable, and approximately 6% of participants discontinued treatment with morphine because of intolerable adverse events. The quality of the evidence is generally poor. Studies are old, often small, and were largely carried out for registration purposes and therefore were only designed to show equivalence between different formulations. The conclusions have not changed for this update. The effectiveness of oral morphine has stood the test of time, but the randomised trial literature for morphine is small given the importance of this medicine. Most trials recruited fewer than 100 participants and did not provide appropriate data for meta-analysis. Only a few reported how many people had good pain relief, but where it was reported, over 90% had no worse than mild pain within a reasonably short time period. The review demonstrates the wide dose range of morphine used in studies, and that a small percentage of participants are unable to tolerate oral morphine. The review also shows the wide range of study designs, and inconsistency in cross-over designs. Trial design was frequently based on titration of morphine or comparator to achieve adequate analgesia, then crossing participants over in cross-over design studies. It was not clear if these trials were sufficiently powered to detect any clinical differences between formulations or comparator drugs. New studies added to the review for the previous update reinforced the view that it is possible to use modified release morphine to titrate to analgesic effect. There is qualitative evidence that oral morphine has much the same efficacy as other available opioids.",
        "gold": "In this updated review we set out to estimate how well morphine worked, how many people had side effects, and how severe those side effects were \u2013 for example, whether they were so severe that participants stopped taking their oral morphine. We found 62 studies with 4241 participants. The studies were often small, compared many different preparations, and used different study designs. This made it difficult to work out whether any one tablet or preparation of oral morphine was better than any other. There did not seem to be much difference between them. More than 9 in 10 participants had pain that went from moderate or severe before taking morphine to pain that was no worse than mild when taking morphine. More than 6 in 10 participants were very satisfied with the morphine treatment, or considered the result to be very good or excellent. Only about 1 person in 20 stopped taking morphine because of side effects. Morphine is associated with some unwanted effects, mainly constipation, and nausea and vomiting. At one level these are good results. On another level, the quality of studies is generally poor and we could wish for more consistency in study design, and especially in study reporting, which should include the outcome of pain reduced to tolerable levels \u2013 no worse than mild pain \u2013 so that people with cancer are not bothered by pain."
    },
    {
        "index": "cochrane-simplification-test-432",
        "sentence": "Fourteen trials were included, totalling 1260 participants, with 1361 trigger fingers. The age of participants included in the studies ranged from 16 to 88 years; and the majority of participants were women (approximately 70%). The average duration of symptoms ranged from three to 15 months, and the follow-up after the procedure ranged from eight weeks to 23 months. The studies reported nine types of comparisons: open surgery versus steroid injections (two studies); percutaneous surgery versus steroid injection (five studies); open surgery versus steroid injection plus ultrasound-guided hyaluronic acid injection (one study); percutaneous surgery plus steroid injection versus steroid injection (one study); percutaneous surgery versus open surgery (five studies); endoscopic surgery versus open surgery (one study); and three comparisons of types of incision for open surgery (transverse incision of the skin in the distal palmar crease, transverse incision of the skin about 2\u20133 mm distally from distal palmar crease, and longitudinal incision of the skin) (one study). Most studies had significant methodological flaws and were considered at high or unclear risk of selection bias, performance bias, detection bias and reporting bias. The primary comparison was open surgery versus steroid injections, because open surgery is the oldest and the most widely used treatment method and considered as standard surgery, whereas steroid injection is the least invasive control treatment method as reported in the studies in this review and is often used as first-line treatment in clinical practice. Compared with steroid injection, there was low-quality evidence that open surgery provides benefits with respect to less triggering recurrence, although it has the disadvantage of being more painful. Evidence was downgraded due to study design flaws and imprecision. Based on two trials (270 participants) from six up to 12 months, 50/130 (or 385 per 1000) individuals had recurrence of trigger finger in the steroid injection group compared with 8/140 (or 65 per 1000; range 35 to 127) in the open surgery group, RR 0.17 (95% CI 0.09 to 0.33), for an absolute risk difference that 29% fewer people had recurrence of symptoms with open surgery (60% fewer to 3% more individuals); relative change translates to improvement of 83% in the open surgery group (67% to 91% better). At one week, 9/49 (184 per 1000) people had pain on the palm of the hand in the steroid injection group compared with 38/56 (or 678 per 1000; ranging from 366 to 1000) in the open surgery group, RR 3.69 (95% CI 1.99 to 6.85), for an absolute risk difference that 49% more had pain with open surgery (33% to 66% more); relative change translates to worsening of 269% (585% to 99% worse) (one trial, 105 participants). Because of very low quality evidence from two trials we are uncertain whether open surgery improve resolution of trigger finger in the follow-up at six to 12 months, when compared with steroid injection (131/140 observed in the open surgery group compared with 80/130 in the control group; RR 1.48, 95% CI 0.79 to 2.76); evidence was downgraded due to study design flaws, inconsistency and imprecision. Low-quality evidence from two trials and few event rates (270 participants) from six up to 12 months of follow-up, we are uncertain whether open surgery increased the risk of adverse events (incidence of infection, tendon injury, flare, cutaneous discomfort and fat necrosis) (18/140 observed in the open surgery group compared with 17/130 in the control group; RR 1.02, 95% CI 0.57 to 1.84) and neurovascular injury (9/140 observed in the open surgery group compared with 4/130 in the control group; RR 2.17, 95% CI 0.7 to 6.77). Twelve participants (8 versus 4) did not complete the follow-up, and it was considered that they did not have a positive outcome in the data analysis. We are uncertain whether open surgery was more effective than steroid injection in improving hand function or participant satisfaction as studies did not report these outcomes. Low-quality evidence indicates that, compared with steroid injection, open surgical treatment in people with trigger finger, may result in a less recurrence rate from six up to 12 months following the treatment, although it increases the incidence of pain during the first follow-up week. We are uncertain about the effect of open surgery with regard to the resolution rate in follow-up at six to 12 months, compared with steroid injections, due high heterogeneity and few events occurred in the trials; we are uncertain too about the risk of adverse events and neurovascular injury because of a few events occurred in the studies. Hand function or participant satisfaction were not reported.",
        "gold": "This Cochrane Review is current to August 2017. We included 14 randomised controlled trials involving 1260 participants, totalling 1361 trigger fingers. Two studies compared open surgery versus steroid injections, five studies compared percutaneous surgery versus steroid injection, one study compared open surgery versus steroid injection plus hyaluronic acid injection, one study compared percutaneous surgery plus steroid injection versus steroid injection, five studies compared percutaneous surgery versus open surgery, one study compared endoscopic surgery versus open surgery and one study compared three types of skin incision to open surgery. The majority of participants were female (about 70%); they were aged between 16 and 88 years; and the mean follow-up of participants after the procedure was eight weeks to 23 months. Due to space constraints, the reporting of all results was limited to the main comparison \u2014 open surgery versus steroid injection \u2014 because open surgery is the oldest and the most widely used treatment method and considered as standard surgery, whereas steroid injection is the least invasive control treatment method as reported in the studies in this review and is often used as first-line treatment in clinical practice. Based on two trial (270 participants), compared with the steroid injection procedure: Resolution of trigger finger (lessening of symptoms with no recurrence): \u2022 92 out of 100 people had resolution of symptoms with open surgery. \u2022 61 out of 100 people had resolution of symptoms with steroid injection. Incidence of pain, assessed as the presence or absence of pain after the procedure was performed (at one week): \u2022 49% more people had pain with open surgery (33% to 66% more). \u2022 68 out of 100 people had pain with open surgery. \u2022 19 out of 100 people had pain with steroid injection. Recurrence of the trigger finger (from six to 12 months): \u2022 29% fewer people had recurrence of symptoms with open surgery (60% fewer to 3% more). \u2022 7 out of 100 people had recurrence of symptoms with open surgery. \u2022 39 out of 100 people had recurrence of symptoms with steroid injection. Adverse events: Adverse events including infections, tendon injuries, cutaneous discomfort, flare or fat necrosis at the procedure site, or neovascular events were uncommon in either treatment group. No study reported hand function or participant-reported treatment success or satisfaction. Very low quality evidence from two trials means we are uncertain whether open surgery improve resolution of trigger finger in comparison with steroid injection, due the risk of bias in the design of the studies, inconsistencies between studies and the small number of participants in studies. Low-quality evidence from two trials shows that open surgery may result in fewer recurrences of trigger finger compared with steroid injection procedure, although it increases the incidence of pain during the first week after the procedure. Evidence was downgraded to 'low' due to the risk of bias in the design and the small number of participants. No studies measured functional improvement or participant satisfaction in the comparison between open surgery and steroid injection. We are uncertain whether there is a difference in the risk of adverse events or neurovascular injury between treatments, as few events occurred in the studies. Only low and very low-quality evidence was found for other comparisons so we are uncertain if percutaneous surgery has any benefits over steroid injection, or if open surgery is better than steroid plus hyaluronic acid, or if one type of surgery is better than another."
    },
    {
        "index": "cochrane-simplification-test-433",
        "sentence": "Three RCTs, with 931 participants, tested different neoadjuvant treatments: RT alone; sequential RT and procarbazine, lomustine and vincristine (PCV) chemotherapy; PCV chemotherapy alone; and temozolomide chemotherapy alone. None of the studies blinded participants or personnel, and, therefore, are considered at high risk of performance and detection bias. The studies were otherwise at low risk of bias. One study, the European Organisation for Research and Treatment of Cancer (EORTC) trial, demonstrated a statistically significant overall survival (OS) benefit for RT plus PCV, with a median OS of 3.5 years compared with 2.6 years in the RT alone arm (P value = 0.018). This result was reported 10 years after the conclusion of the enrolment, and was not apparent in the original 2008 Cochrane review. Furthermore, with retrospective evaluation of biomarkers, codeletion of complete chromosome arms 1p and 19q and IDH-1 or -2 mutation were independent prognostic factors for OS in two of the RCTs (Radiation Therapy Oncology Group (RTOG) and EORTC), and were predictive for OS in one trial (RTOG). The third trial (NOA-04) evaluated these biomarkers prospectively and found them prognostic for progression-free survival. Early PCV, either before or after RT, appears to improve OS of participants with AO or AOA. Use of biomarkers including codeletion of chromosomes 1p and 19q with or without IDH-1 or -2 mutation identify a subset of people with increased sensitivity to combined PCV and RT. The important role of biomarkers was supported in all of the RCTs examined, and prospective evaluation should be undertaken in future studies. However, PCV was associated with significant grade 3 and 4 toxicities, and whether temozolomide can be substituted for this remains unclear.",
        "gold": "We searched the scientific literature up to March 2014 for studies of adults over 18 years of age with a diagnosis of anaplastic oligodendrogliomas, anaplastic oligoastrocytomas or anaplastic astrocytomas. After surgery, the participants had to have received radiotherapy alone, chemotherapy alone or radiotherapy plus chemotherapy. In the first review on this topic in 2009, we found two trials to include. In this update, we identified another trial for inclusion, and updates from the two previously included trials were taken into consideration. Three randomized controlled trials, which included 931 participants, assessed the role of chemotherapy alone or in addition to radiotherapy, or radiotherapy alone. One study was able to demonstrate a significant survival benefit for the addition of chemotherapy to radiotherapy after surgery, compared with radiotherapy alone. In addition, during examination of these brain tumour biopsy specimens, they found specific chromosome deletions and mutations in two studies, which helped to identify a group of participants with better survival outcomes. Furthermore, in one study, these specific chromosome deletions and mutations predicted which group of participants derived benefit from the addition of chemotherapy to radiotherapy after surgery. Evidence for giving radiotherapy and chemotherapy was of good quality, but sparse."
    },
    {
        "index": "cochrane-simplification-test-434",
        "sentence": "We included five trials with a total of 240 children aged one to 18 years with mild to moderate OSA (AHI 1 to 30 per hour). All trials were performed in specialised sleep medicine clinics at tertiary care centres. Follow-up time ranged from six weeks to four months. Three RCTs (n = 137) compared intranasal steroids against placebo; two RCTs compared oral montelukast against placebo (n = 103). We excluded one trial from the meta-analysis since the patients were not analysed as randomised. We also had concerns about selective reporting in another trial. We are uncertain about the difference in AHI (MD \u22123.18, 95% CI \u22128.70 to 2.35) between children receiving intranasal corticosteroids compared to placebo (2 studies, 75 participants; low-certainty evidence). In contrast, children receiving oral montelukast had a lower AHI (MD \u22123.41, 95% CI \u22125.36 to \u22121.45) compared to those in the placebo group (2 studies, 103 participants; moderate-certainty evidence). We are uncertain whether the secondary outcomes are different between children receiving intranasal corticosteroids compared to placebo: desaturation index (MD \u22122.12, 95% CI \u22124.27 to 0.04; 2 studies, 75 participants; moderate-certainty evidence), respiratory arousal index (MD \u22120.71, 95% CI \u22126.25 to 4.83; 2 studies, 75 participants; low-certainty evidence), and nadir oxygen saturation (MD 0.59%, 95% CI \u22121.09 to 2.27; 2 studies, 75 participants; moderate-certainty evidence). Children receiving oral montelukast had a lower respiratory arousal index (MD \u22122.89, 95% CI \u22124.68 to \u22121.10; 2 studies, 103 participants; moderate-certainty evidence) and nadir of oxygen saturation (MD 4.07, 95% CI 2.27 to 5.88; 2 studies, 103 participants; high-certainty evidence) compared to those in the placebo group. We are uncertain, however, about the difference in desaturation index (MD \u22122.50, 95% CI \u22125.53 to 0.54; 2 studies, 103 participants; low-certainty evidence) between the montelukast and placebo group. Adverse events were assessed and reported in all trials and were rare, of minor nature (e.g. nasal bleeding), and evenly distributed between study groups. No study examined the avoidance of surgical treatment for OSA as an outcome. There is insufficient evidence for the efficacy of intranasal corticosteroids for the treatment of OSA in children; they may have short-term beneficial effects on the desaturation index and oxygen saturation in children with mild to moderate OSA but the certainty of the benefit on the primary outcome AHI, as well as the respiratory arousal index, was low due to imprecision of the estimates and heterogeneity between studies. Montelukast has short-term beneficial treatment effects for OSA in otherwise healthy, non-obese, surgically untreated children (moderate certainty for primary outcome and moderate and high certainty, respectively, for two secondary outcomes) by significantly reducing the number of apnoeas, hypopnoeas, and respiratory arousals during sleep. In addition, montelukast was well tolerated in the children studied. The clinical relevance of the observed treatment effects remains unclear, however, because minimal clinically important differences are not yet established for polysomnography-based outcomes in children. Long-term efficacy and safety data on the use of anti-inflammatory medications for the treatment of OSA in childhood are still not available. In addition, patient-centred outcomes like concentration ability, vigilance, or school performance have not been investigated yet. There are currently no RCTs on the use of other kinds of anti-inflammatory medications for the treatment of OSA in children. Future RCTs should investigate sustainability of treatment effects, avoidance of surgical treatment for OSA, and long-term safety of anti-inflammatory medications for the treatment of OSA in children and include patient-centred outcomes.",
        "gold": "We included five studies in the review. These studies each included 25 to 62 children between one and 11 years of age with mild to moderate OSA treated at specialised sleep outpatient clinics. The included studies used two different types of anti-inflammatory medications. Seventy-five children were randomised to receive either intranasal corticosteroid nasal spray or placebo. One hundred and three children were randomised to either montelukast tablet or placebo. Three studies were supported by drug manufacturers. We are uncertain about the difference in the number of breathing pauses, episodes of shallow breathing, episodes with a lack of blood oxygen, or sleep disruption between children receiving corticosteroid nasal spray compared to placebo (2 studies involving 75 children). Children receiving montelukast tablets had fewer breathing pauses, fewer episodes of shallow breathing, and less sleep disruption compared to those treated with placebo (2 studies involving 103 children). However, we are uncertain about the difference in the number of episodes with a lack of blood oxygen between the montelukast and placebo group. Unintended effects were assessed in all trials, but were rare and of minor nature (e.g. nosebleeds). Serious unintended effects were not reported. The certainty of the evidence for corticosteroid nasal spray for the treatment of OSA was low for the primary outcome due to the wide range of the beneficial effect with some inconsistency of the effect between the two included studies. We excluded one study from the analysis due to serious concerns about the quality of the study results. The evidence for the use of montelukast tablets in the treatment of OSA was of moderate certainty for the primary outcome. There were concerns about the design and conduct of one study and some inconsistency of the effect between the two included studies. The evidence is current to October 2019."
    },
    {
        "index": "cochrane-simplification-test-435",
        "sentence": "Three RCTs and three CCTs (including 1291 children) investigated the prevention of VTE (low molecular weight heparin (LMWH) n = 134, antithrombin (AT) supplementation n = 37, low-dose warfarin n = 31, cryoprecipitate and/or fresh frozen plasma (FFP) supplementation n = 240, AT supplementation and LMWH n = 41). AT, cryoprecipitate and FFP were supplemented only in cases of AT or fibrinogen deficiency. Of the six included RCTs/CCTs, five investigated the prevention of VTE compared with no intervention (n = 737), and one CCT compared AT supplementation and LMWH with AT supplementation (n = 71). All studies had methodological limitations, and clinical heterogeneity between studies was noted. We found no significant effects of systemic treatments compared with no intervention in preventing (a)symptomatic VTE and no differences in adverse events (such as major and/or minor bleeding; none of the studies reported thrombocytopenia, heparin-induced thrombocytopenia (HIT), heparin-induced thrombocytopenia with thrombosis (HITT), death as a result of VTE, removal of CVC due to VTE, CVC-related infection, and post-thrombotic syndrome (PTS)) between experimental and control groups. Two studies with comparable participant groups and interventions were included for meta-analyses (n = 182). In the experimental group, 1/68 (1.5%) children were diagnosed with symptomatic VTE, as were 4/114 (3.5%) in the control group (best case scenario: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.09 to 4.78). These studies also evaluated asymptomatic CVC-related VTE: In the experimental group, 22/68 (32.4%) were diagnosed with asymptomatic VTE, as were 35/114 (30.7%) in the control group (best case scenario: RR 1.02, 95% CI 0.40 to 2.55). Heterogeneity was substantial for this analysis: I2 = 73%. The attribution of LMWH to AT supplementation resulted in a significant reduction in symptomatic VTE (Fisher's exact test, two-sided P = 0.028) without bleeding complications; asymptomatic VTE, thrombocytopenia, HIT, HITT, death as a result of VTE, removal of CVC due to VTE, CVC-related infection and PTS were not assessed. Four cohort studies were included for the evaluation of adverse events. Three studies provided information on bleeding episodes: One participant developed an ischaemo-haemorrhagic stroke. One study provided information on other adverse events: None occurred. We found no significant effects of systemic treatments compared with no intervention in preventing (a)symptomatic VTE in paediatric oncology patients with CVCs. However, this could be a result of the low number of included participants, which resulted in low power. In one CCT, which compared one systemic treatment with another systemic treatment, we identified a significant reduction in symptomatic VTE with the addition of LMWH to AT supplementation. All studies investigated the prevalence of major and/or minor bleeding episodes, and none found a significant difference between study groups. None of the studies reported thrombocytopenia, HIT, HITT, death as a result of VTE, removal of CVC due to VTE, CVC-related infection or PTS among participants. On the basis of currently available evidence, we are not able to give recommendations for clinical practise. Additional well-designed international RCTs are needed to further explore the effects of systemic treatments in preventing VTE. Future studies should aim for adequate power with attainable sample sizes. The incidence of symptomatic VTE is relatively low; therefore, it might be necessary to select participants with thrombotic risk factors or to investigate asymptomatic VTE instead.",
        "gold": "In this review, we investigated whether systemic treatments can prevent thrombosis. We identified six studies; two studies investigated low molecular weight heparins, one antithrombin supplementation and one cryoprecipitate and/or fresh frozen plasma supplementation; one study compared antithrombin supplementation with low molecular weight heparin and antithrombin supplementation, and another investigated warfarin. The addition of low molecular weight heparins to antithrombin supplementation did result in a lower number of symptomatic thromboses. This was statistically significant. We could not detect an effect of systemic preventive treatments in comparison with no treatment, and no difference was noted in the number of participants who suffered from major or minor bleeding. However, the overall number of participants was very small; a similar study with a larger population of participants might yield different results."
    },
    {
        "index": "cochrane-simplification-test-436",
        "sentence": "Three trials with a total of 287 participants operated on for Type I or II TAAA were included. In the first trial of 98 participants, neurological deficits in the lower extremities occurred in 14 (30%) of CSFD group and 17 (33%) controls. The deficit was observed within 24 hours of the operation in 21 (68%), and from three to 22 days in 10 (32%) participants. CSFD did not have a significant benefit in preventing ischaemic injury to the spinal cord. The second trial of 33 participants used a combination of CSFD and intrathecal papaverine. It showed a statistically significant reduction in the rate of postoperative neurological deficit (P = 0.039), compared to controls. Analysis was undertaken after only one third of the estimated sample size had entered the trial. In the third trial TAAA repair was performed on 145 participants. CSFD was initiated during the operation and continued for 48 hours after surgery. Paraplegia or paraparesis occurred in 9 of 74 participants (12.2%) in the control group versus 2 of 82 participants (2.7%) receiving CSFD (P = 0.03). Overall, CSFD resulted in an 80% reduction in the relative risk of postoperative deficits. Meta-analysis showed an odds ratio (OR) of 0.48 (95 % confidence interval (CI) 0.25 to 0.92). For CSFD-only trials, OR was 0.57 (95% CI 0.28 to 1.17) and for intention-to-treat analysis in CSFD-only studies, the OR remained unchanged. There are limited data supporting the role of CSFD in thoracic and thoracoabdominal aneurysm surgery for prevention of neurological injury. Further clinical and experimental studies are indicated.",
        "gold": "The available evidence does not fully establish CSF drainage as a method of protection. The review authors made a thorough search of the medical literature and identified three randomised trials involving a total of 287 participants operated on for high-risk thoracoabdominal aortic aneurysms. All of the studies used CSF drainage in addition to other measures of spinal cord protection. In the first trial of 98 patients, neurological deficits in the lower extremities occurred in about one third of patients with or without drainage. The deficit was observed within 24 hours of the operation in 21 (68%), and from three to 22 days in 10 (32%). The second trial of 33 patients reported that a combination of CSF drainage and papaverine in the region of the spinal cord (intrathecally) reduced the rate of postoperative neurological deficit compared to controls. In the third trial involving 145 patients, drainage was begun during the operation and continued for 48 hours after surgery. Paraplegia or paraparesis occurred less with CSF drainage (2.7% of patients with drainage versus 12.2% in the control group)."
    },
    {
        "index": "cochrane-simplification-test-437",
        "sentence": "We included 13 RCTs, with a total of 662 participants. We report the results of intention-to-treat analyses (ITT) here. Our primary outcomes of interest were as follows: Participant-rated global improvement, Percentage of participants reaching Psoriasis Area and Severity Index (PASI) 75 (which meant equal to or more than 75% reduction in PASI score), Withdrawal due to side-effects, and Clearance rate. In one RCT of NB-UVB compared with oral PUVA in participants with CPP, the difference in PASI 75 was not statistically significant (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.63 to 1.32; N = 51; low quality). In three other RCTs of CPP, the clearance rates were inconsistent because in one, there was no difference between the groups (RR 1.01, 95% CI 0.91 to 1.12; N = 54), and in the other two, the clearance rates were statistically significantly in favour of oral PUVA: RR 0.66, 95% CI 0.47 to 0.93; N = 93 and RR 0.75, 95% CI 0.59 to 0.96; N = 100, respectively. Pooled data from these three studies indicated that withdrawals due to adverse events were not significantly different between either group (RR 0.71, 95% CI 0.20 to 2.54; N = 247; low quality). The evidence from the comparison of NB-UVB with bath PUVA in terms of clearance rate for CPP was also inconsistent: Pooled data from two left-right body comparison RCTs found no significant difference between the NB-UVB and bath PUVA groups (RR 1.79, 95% CI 0.46 to 6.91; N = 92; low quality), while a parallel RCT favoured bath PUVA (RR 0.18, 95% CI 0.05 to 0.71; N = 36; low quality). In participants with PPP, one RCT found there were no significant differences between NB-UVB treated sides and topical PUVA treated sides in terms of clearance rate (RR 0.09, 95% CI 0.01 to 1.56; N = 50; low quality). Two RCTs found NB-UVB plus retinoid (re-NB-UVB) and PUVA plus retinoid (re-PUVA) had similar effects for treating people with CPP or GP in terms of clearance rate (RR 0.93, 95% CI 0.79 to 1.10; N = 90; low quality). One RCT in people with CPP found no significant differences between NB-UVB and selective BB-UVB in terms of clearance rate (RR 1.40, 95% CI 0.92 to 2.13; N = 100; low quality) and withdrawals due to adverse events (RR 3.00, 95% CI 0.32 to 27.87; N = 100; low quality). No studies reported our primary outcomes for NB-UVB compared with conventional BB-UVB. Current evidence is very heterogeneous and needs to be interpreted with caution. The clearance rate between oral PUVA and NB-UVB is inconsistent among the included studies. Evidence regarding NB-UVB versus bath PUVA is also inconsistent. Re-NB-UVB and re-PUVA are similarly effective for treating people with CPP or GP. In practice, NB-UVB may be more convenient to use since exogenous photosensitiser is not required before phototherapy. NB-UVB is considered ineffective for PPP in clinical practice, and a small RCT did not detect a statistically significant difference between NB-UVB and topical PUVA for clearing PPP. NB-UVB seemed to be similar to selective BB-UVB for clearing CPP. Larger prospective studies are needed to confirm the long-term safety of NB-UVB.",
        "gold": "This review included 13 small randomised controlled trials (RCT), with a total of 662 participants. Most of these were of poor methodological quality. For treating CPP, the clearance rate between the NB-UVB and oral PUVA groups were inconsistent in three RCTs. In one, there was no difference between the groups, and in the other two, the clearance rate was in favour of oral PUVA. The evidence from the comparison of NB-UVB with bath PUVA in terms of clearance rate was also inconsistent: Pooled data from two left-right body comparison RCTs found no significant difference between the two groups, while another RCT favoured bath PUVA. Two RCTs found NB-UVB plus retinoid (re-NB-UVB) and PUVA plus retinoid (re-PUVA) had similar effects for treating people with CPP or guttate psoriasis. One RCT found no significant differences between NB-UVB and selective BB-UVB for clearing CPP or in the number of withdrawals due to side-effects. In participants with PPP, one RCT found there were no statistically significant differences between NB-UVB treated sides and topical PUVA treated sides in terms of clearance rate. In summary, NB-UVB may be preferred to oral or bath PUVA because it is more convenient to use. NB-UVB seemed to be equal to selective BB-UVB for clearing CPP. Evidence regarding NB-UVB and conventional BB-UVB is limited. The long-term safety of NB-UVB needs to be confirmed. The efficacy of NB-UVB for clearing PPP needs to be confirmed in future studies."
    },
    {
        "index": "cochrane-simplification-test-438",
        "sentence": "Twenty one eligible studies were identified with a total of 1525 participants. About half of the trials had low risk of bias for randomisation and allocation concealment. One small trial showed that biofeedback plus exercises was better than exercises alone (RR for failing to achieve full continence 0.70, 95% CI 0.52 to 0.94). One small trial showed that adding biofeedback to electrical stimulation was better than electrical stimulation alone (RR for failing to achieve full continence 0.47, 95% CI 0.33 to 0.65). The combined data of two trials showed that the number of people failing to achieve full continence was significantly lower when electrical stimulation was added to biofeedback compared against biofeedback alone (RR 0.60, 95% CI 0.46 to 0.78). Sacral nerve stimulation was better than conservative management which included biofeedback and PFMT (at 12 months the incontinence episodes were significantly fewer with sacral nerve stimulation (MD 6.30, 95% CI 2.26 to 10.34). There was not enough evidence as to whether there was a difference in outcome between any method of biofeedback or exercises. There are suggestions that rectal volume discrimination training improves continence more than sham training. Further conclusions are not warranted from the available data. The limited number of identified trials together with methodological weaknesses of many do not allow a definitive assessment of the role of anal sphincter exercises and biofeedback therapy in the management of people with faecal incontinence. We found some evidence that biofeedback and electrical stimulation may enhance the outcome of treatment compared to electrical stimulation alone or exercises alone. Exercises appear to be less effective than an implanted sacral nerve stimulator. While there is a suggestion that some elements of biofeedback therapy and sphincter exercises may have a therapeutic effect, this is not certain. Larger well-designed trials are needed to enable safe conclusions.",
        "gold": "There was some evidence from trials suggesting that these treatments are helpful. If patients who have tried and failed other simpler treatments, such as changing their diet or using medications, are selected then biofeedback using computer equipment or rectal balloon is more beneficial than exercises alone. Exercises and electrical stimulation used in the anus may be more helpful than vaginal exercises for women with faecal incontinence after childbirth. About half of the 21 trials were at low risk of bias. They compared different combinations of treatments and different outcome measures, making comparison between them difficult. However, a small number of the larger recent trials provide better evidence."
    },
    {
        "index": "cochrane-simplification-test-439",
        "sentence": "Thirty nine randomised trials were identified for inclusion in the review. They were generally small and of poor or moderate quality reporting data on only few outcomes. Confidence intervals were all wide. Using a urinary catheter versus not using one  The data from five trials were heterogeneous but tended to indicate a higher risk of (re)catheterisation if a catheter was not used postoperatively. The data gave only an imprecise estimate of any difference in urinary tract infection. Urethral catheterisation versus suprapubic catheterisation  In six trials, a greater number of people needed to be recatheterised if a urethral catheter rather than a suprapubic one was used following surgery (RR 3.66, 95% CI 1.41 to 9.49). Shorter postoperative duration of catheter use versus longer duration  In 11 trials, the seven trials with data suggested fewer urinary tract infections when a catheter was removed earlier (for example 1 versus 3 days, RR 0.50, 95% CI 0.29 to 0.87) with no pattern in respect of catheterisation.   Clamp and release policies before catheter removal versus immediate catheter removal  In a single small trial, the clamp-and-release group showed a significantly greater incidence of urinary tract infections (RR 4.00, 95% 1.55 to 10.29) and a delay in return to normal voiding (RR 2.50, 95% CI 1.16 to 5.39). Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.",
        "gold": "Five trials suggested that it might be better to use a catheter after surgery than not to use one as fewer people needed to be re-catheterised if a catheter was used at first. Information from six trials suggested that fewer people needed to be re-catheterised for urinary retention if a suprapubic catheter was used instead of a urethral one. People in up to 11 trials had fewer urinary tract infections if the catheters were removed sooner rather than later.   Although 39 trials were included in the review in total, the evidence in general was poor and came from small studies, which often did not provide enough information to draw firm conclusions. Much larger trials with many more participants must be conducted."
    },
    {
        "index": "cochrane-simplification-test-440",
        "sentence": "Ten studies (3340 participants) were included in the review. Seven studies compared aripiprazole monotherapy versus placebo (2239 participants); two of these included a third comparison arm\u2014one study used lithium (485 participants) and the other used haloperidol (480 participants). Two studies compared aripiprazole as an adjunctive treatment to valproate or lithium versus placebo as an adjunctive treatment (754 participants), and one study compared aripiprazole versus haloperidol (347 participants). The overall risk of bias was unclear. A high dropout rate from most trials (> 20% for each intervention in eight of the trials) may have affected the estimates of relative efficacy. Evidence shows that aripiprazole was more effective than placebo in reducing manic symptoms in adults and children/adolescents at three and four weeks but not at six weeks (Young Mania Rating Scale (YMRS); mean difference (MD) at three weeks (random effects) -3.66, 95% confidence interval (CI) -5.82 to -2.05; six studies; N = 1819, moderate quality evidence) - a modest difference. Aripiprazole was compared with other drug treatments in three studies in adults\u2014lithium was used in one study and haloperidol in two studies. No statistically significant differences between aripiprazole and other drug treatments in reducing manic symptoms were noted at three weeks (YMRS MD at three weeks (random effects) 0.07, 95% CI -1.24 to 1.37; three studies; N = 972, moderate quality evidence) or at any other time point up to and including 12 weeks. Compared with placebo, aripiprazole caused more movement disorders, as measured on the Simpson Angus Scale (SAS), on the Barnes Akathisia Scale (BAS) and by participant-reported akathisia (high quality evidence), with more people requiring treatment with anticholinergic medication (risk ratios (random effects) 3.28, 95% CI 1.82 to 5.91; two studies; N = 730, high quality evidence). Aripiprazole also led to more gastrointestinal disturbances (nausea (high quality evidence), and constipation) and caused more children/adolescents to have a prolactin level that fell below the lower limit of normal. Significant heterogeneity was present in the meta-analysis of movement disorders associated with aripiprazole and other treatments and was most likely due to the different side effect profiles of lithium and haloperidol. At the three-week time point, meta-analysis was not possible because of lack of data; however, at 12 weeks, haloperidol resulted in significantly more movement disorders than aripiprazole, as measured on the SAS, the BAS and the Abnormal Involuntary Movement Scale (AIMS) and by participant-reported akathisia. By 12 weeks, investigators reported no difference between aripiprazole and lithium (SAS, BAS, AIMS), except in terms of participant-reported akathisia (RR 2.97, 95% CI 1.37 to 6.43; one study; N = 313). Aripiprazole is an effective treatment for mania in a population that includes adults, children and adolescents, although its use leads to gastrointestinal disturbances and movement disorders. Comparative trials with medicines other than haloperidol and lithium are few, so the precise place of aripiprazole in therapy remains unclear.",
        "gold": "Ten studies are included (3340 participants). Most studies compared aripiprazole versus placebo, but some researchers compared aripiprazole versus haloperidol (two studies) and versus lithium (one study). Two studies examined the effect of adding aripiprazole to another treatment (valproate or lithium) and compared this combination versus placebo combined with these other treatments. We assessed the overall risk of bias in the ten studies as unclear. The main measure of effect was the mean change on the Young Mania Rating Scale from the start to the end of the trial; this tool is used by clinicians to assess the severity of mania. After three weeks of treatment, aripiprazole was better than placebo at reducing the severity of mania when used on its own or when added to other mood stabilisers. The effect was modest. However, aripiprazole caused more inner restlessness (akathisia), nausea, and constipation than placebo. Aripiprazole was similarly effective in reducing the symptoms of mania when compared with other drug treatments (haloperidol and lithium). Aripiprazole caused fewer movement disorders and less raised prolactin (a hormone secreted by the pituitary gland) than haloperidol. People taking aripiprazole were more likely to remain on treatment than those taking haloperidol but were no more or less likely than those taking placebo or lithium. The main reason for the difference in dropouts between aripiprazole and haloperidol groups was the adverse effects associated with haloperidol. In summary, aripiprazole is an effective treatment for mania when compared with placebo. This finding is based on studies that included mixed populations (i.e. children, adolescents and adults). For the adult population, studies have directly compared aripiprazole versus haloperidol, lithium and placebo, but evidence obtained for treatment of the child and adolescent population is available only from placebo-controlled studies. Given the lack of evidence obtained by comparing aripiprazole versus other drugs, its exact place in therapy is unclear. Further studies focused on particular populations are needed to determine whether this treatment is equally effective in different age groups."
    },
    {
        "index": "cochrane-simplification-test-441",
        "sentence": "Two RCTs evaluated urokinase lock treatment with concomitant systemic antibiotics (n = 56) versus systemic antibiotics alone (n = 48), and one CCT evaluated ethanol lock treatment with concomitant systemic antibiotics (n = 15) versus systemic antibiotics alone (n = 13). No RCTs or CCTs evaluating antibiotic lock treatments were identified. All studies had methodological limitations and clinical heterogeneity between studies was present. We found no evidence of significant difference between ethanol or urokinase lock treatments with concomitant systemic antibiotics and systemic antibiotics alone regarding the number of participants cured, the number of recurrent CVC-related infections, the number of days until the first negative blood culture, the number of CVCs prematurely removed, ICU admission and sepsis. Not all studies were included in all analyses. No adverse events occurred in the five publications of cohort studies (one cohort was included in two publications) assessing this outcome; CVC malfunctioning occurred in three out of five publications of cohort studies assessing this outcome. No significant effect of urokinase or ethanol lock in addition to systemic antibiotics was found. However, this could be due to low power or a too-short follow-up. The cohort studies identified no adverse events; some cohort studies reported CVC malfunctioning. No RCTs or CCTs were published on antibiotic lock treatment alone. More well-designed RCTs are needed to further explore the effect of antibiotic or other lock treatments in the treatment of CVC-related infections in children with cancer.",
        "gold": "In this review we investigated the effect of lock treatments on CVC-related infections. We identified three studies: two investigating the effect of urokinase lock treatments in addition to antibiotics and one study investigating the effect of ethanol locks in addition to antibiotics. We could detect no effect of urokinase or ethanol locks. However, the groups were very small. A similar study with a larger participant population might have different results."
    },
    {
        "index": "cochrane-simplification-test-442",
        "sentence": "Of the 15 selected trials, three were rated low risk of bias. Three TPE themes emerged. Advice focusing on activation: There is moderate quality evidence (one trial, 348 participants) that an educational video of advice focusing on activation was more beneficial for acute whiplash-related pain when compared with no treatment at intermediate-term [RR 0.79 (95% confidence interval (CI) 0.59 to 1.06)] but not long-term follow-up [0.89 (95% CI, 0.65 to 1.21)]. There is low quality evidence (one trial, 102 participants) that a whiplash pamphlet on advice focusing on activation is less beneficial for pain reduction, or no different in improving function and global perceived improvement from generic information given out in emergency care (control) for acute whiplash at short- or intermediate-term follow-up. Low to very low quality evidence (nine trials using diverse educational approaches) showed either no evidence of benefit or difference for varied outcomes. Advice focusing on pain & stress coping skills and workplace ergonomics: Very low quality evidence (three trials, 243 participants) favoured other treatment or showed no difference spanning numerous follow-up periods and disorder subtypes.\u00a0 Low quality evidence (one trial, 192 participants) favoured specific exercise training for chronic neck pain at short-term follow-up. Self-care strategies: Very low quality evidence (one trial, 58 participants) indicated that self-care strategies did not relieve pain for acute to chronic neck pain at short-term follow-up. With the exception of one trial, this review has not shown effectiveness for educational interventions, including advice to activate, advice on stress-coping skills, workplace ergonomics and self-care strategies. Future research should be\u00a0founded on sound adult learning theory and learning skill acquisition.",
        "gold": "Electronic bibliographic databases were searched up to 11 July 2010. Fifteen randomised controlled trials (1660 participants) looking at the effectiveness of patient education strategies for neck disorders were included. Of the 15 selected trials, only one trial depicting moderate quality evidence favoured the educational video for acute WAD. The remaining trials showed that patient education trials did not demonstrate evidence of benefit or favoured the comparison treatment being exercise for pain. Other outcomes were less frequently reported and did not yield results that diverged from those associated with pain. Participants who received advice to stay active reported little or no difference in pain compared with those who received no treatment, treatments focusing on rest, treatments focusing on exercise, physiotherapy and cognitive behavioural therapy. Additionally, stress-management therapies, when compared with no treatment, did not seem to have an effect on pain intensity in patients with mechanical neck disorders. Finally, self-care strategies (ergonomics, exercise, self-care, relaxation) do not seem to have an effect on pain when compared with no treatment. No adverse events were reported in the trials. In summary, the review authors concluded that there is no strong evidence for the effectiveness of educational interventions in various neck disorders."
    },
    {
        "index": "cochrane-simplification-test-443",
        "sentence": "Results of the Cochrane review No studies meeting the study design criteria were identified for inclusion in this Cochrane review. Results of thematic synthesis In total, 49 studies and pieces of literature meeting the same population, intervention and outcome criteria as the Cochrane review, but identified from the broader literature providing evidence on policy implementation and consumer experiences, were included and formed the basis of a thematic synthesis, and which is presented in appendices to this Cochrane review. The thematic synthesis indicates that ideally communication may be considered as a longitudinal multicomponent programme, ensuring that notification and support are coordinated; that communication is tailored and responsive to need; and that activities to support individual risk communication, such as widespread education and monitoring of access to health care for those at risk, are in place. The thematic synthesis also indicates that poor communication practices may have negative impacts or cause harm, such as discrimination in accessing health care. There is insufficient rigorous evidence to determine the effects of interventions to notify people at CJD or vCJD risk and to support them subsequently, or to identify the best approach to communication in these situations. The thematic synthesis can be used to inform policy and practice decisions for communicating with people at risk in the absence of rigorous evaluative studies.",
        "gold": "That CJD and vCJD are very rare diseases creates challenges for researchers aiming to conduct rigorous quantitative studies in this area. Although we searched widely to identify all relevant research evaluating the effects of interventions to communicate with (notify and support) people at risk, we did not identify any studies that met the criteria for inclusion in this Cochrane review. However, systematic searches did identify a number of pieces of relevant research and literature that provided evidence about policy implementation and consumer experiences in situations of iatrogenic exposure to risk. This research formed the basis of a thematic synthesis. The synthesis identified several activities that aim to improve the experiences of people at risk of CJD and vCJD. It indicates that communication may be best considered as a longitudinal multicomponent programme occurring over time, ensuring that notification is coordinated and considers impact; that support is in place and is offered over time; that communication is flexible, tailored and responsive to need; and that supporting activities, such as widespread education of the healthcare workforce, the public and the media, and monitoring of access to health care for those at risk, are in place. The thematic synthesis also indicates that poor communication practices may have negative impacts or cause harm, such as discrimination in accessing health care. In the absence of rigorous evaluative studies the results of this thematic synthesis can be used to inform policy and practice decisions for communicating with people at risk."
    },
    {
        "index": "cochrane-simplification-test-444",
        "sentence": "We included one randomised clinical trial (N = 304 randomised; 204 completed; 276 analysed) that evaluated opioids (prolonged release oxycodone/naloxone) versus placebo. After 12 weeks, RSL symptoms had improved more in the drug group than in the placebo group (using the IRLSSS: MD -7.0; 95% CI -9.69 to -4.31 and the CGI: MD -1.11; 95% CI -1.49 to -0.73). More patients in the drug group than in the placebo group were drug responders (using the IRLSSS: RR 1.82; 95% CI 1.37 to 2.42 and the CGI: RR1.92; 95% ICI 1.49 to 2.48). The proportion of remitters was greater in the drug group than in the placebo group (using the IRLSSS: RR 2.14; 95% CI 1.45 to 3.16). Quality of life scores also improved more in the drug group than in the placebo group (MD -0.73; 95% CI -1.1 to -0.36). Quality of sleep was improved more in the drug group measured by sleep adequacy (MD -0.74; 95% CI -1.15 to -0.33), and sleep quantity (MD 0.89; 95% CI 0.52 to 1.26). There was no difference between groups for daytime somnolence, trouble staying awake during the day, or naps during the day. More adverse events were reported in the drug group (RR 1.22; 95% CI 1.07 to 1.39). The major adverse events were gastrointestinal problems, fatigue, and headache. Opioids seem to be effective for treating RLS symptoms, but there are no definitive data regarding the important problem of safety. This conclusion is based on only one study with a high dropout rate (low quality evidence).",
        "gold": "We included one randomised controlled clinical trial with moderate risk of bias that tested a combination of oxycodone and naloxone against placebo capsules, taken twice daily in participants whodid not respond to more usual medications. Researchers used the International RLS severity scale to find out if patients were improved after 12 weeks of treatment. Particpants receiving the combined oxycodone and naloxone reported improvement in RLS symptoms, Quality of life, and sleep quality; 42% of the drug group were symptom-free. Discussion The study was well designed overall, but was at a high risk of bias due to the high percentage of participants who withdrew from treatment (attrition bias). Eighty-four percent of the drug group developed adverse events, which were mostly related to the gastrointestinal system, headache, fatigue, and sleepiness (somnolence); 9.8% left the study because of the adverse events. Conclusion The use of opioids for the treatment of RLS in patients resistant to conventional treatment is supported by low-quality evidence. Prescription of these medications should be based on clinical experience, and caution used due to the potential for abuse, dependency, and adverse events. No patient on opioids complained that their symptoms worsened."
    },
    {
        "index": "cochrane-simplification-test-445",
        "sentence": "Fifteen heterogeneous trials, involving 1022 adults with dorsally displaced and potentially or evidently unstable distal radial fractures, were included. While all trials compared external fixation versus plaster cast immobilisation, there was considerable variation especially in terms of patient characteristics and interventions. Methodological weaknesses among these trials included lack of allocation concealment and inadequate outcome assessment. External fixation maintained reduced fracture positions (redisplacement requiring secondary treatment: 7/356 versus 51/338 (data from 9 trials); relative risk 0.17, 95% confidence interval 0.09 to 0.32) and prevented late collapse and malunion compared with plaster cast immobilisation. There was insufficient evidence to confirm a superior overall functional or clinical result for the external fixation group. External fixation was associated with a high number of complications, such as pin-track infection, but many of these were minor. Probably, some complications could have been avoided using a different surgical technique for pin insertion. There was insufficient evidence to establish a difference between the two groups in serious complications such as reflex sympathetic dystropy: 25/384 versus 17/347 (data from 11 trials); relative risk 1.31, 95% confidence interval 0.74 to 2.32. There is some evidence to support the use of external fixation for dorsally displaced fractures of the distal radius in adults. Though there is insufficient evidence to confirm a better functional outcome, external fixation reduces redisplacement, gives improved anatomical results and most of the excess surgically-related complications are minor.",
        "gold": "Fifteen trials, involving 1022 adults with potentially or evidently unstable fractures, were included. While all trials compared external fixation versus plaster cast immobilisation, there was considerable variation in their characteristics especially in terms of patient characteristics and the method of external fixation. Weak methodology, such as using inadequate methods of randomisation and outcome assessment, means that the possibility of serious bias can not be excluded. The review found that external fixation reduced fracture redisplacement that prompted further treatment and generally improved final anatomical outcome. It appears to improve function too but this needs to be confirmed. The complications, such a pin tract infection, associated with external fixation were many but were generally minor. Serious complications occurred in both groups. The review concludes that there is some evidence to support the use of external fixation for these fractures."
    },
    {
        "index": "cochrane-simplification-test-446",
        "sentence": "Five studies (1127 patients) were included in our analysis. Generally the risk of bias of the included studies was judged low or unclear; they addressed the research question and utilised a prospective randomised design. It is uncertain whether early stent removal verus late stent removal improved the incidence of MUC (5 studies, 1127 participants: RR 1.87, 95% CI 0.61 to 5.71; I2 = 21%; low certainty evidence). The incidence of UTI may be reduced in the early stent removal group (5 studies, 1127 participants: RR 0.49 95% CI 0.30 to 0.81; I2 = 59%; moderate certainty evidence). This possible reduction in the UTI incidence was only apparent if a BI stent was used, (3 studies, 539 participants, RR 0.45 95% CI 0.29 to 0.70; I2 = 13%; moderate certainty evidence). However, if an externalised PU stent was used there was no discernible difference in UTI incidence between the early and late group (2 studies, 588 participants: RR 0.60 95% CI 0.17, 2.03; I2 = 83%; low certainty evidence). Data on health economics and quality of life outcomes were lacking. Early removal of ureteric stents following kidney transplantation may reduce the incidence of UTI while it uncertain if there is a higher risk of MUC. BI stents are the optimum method for achieving this benefit.",
        "gold": "It is uncertain whether the number of major urological complications were different in those patients whose stent was removed early (less than 15 days post-operatively), when compared with those removed later (more than 15 days post-operatively). The number of patients suffering from a urinary tract infection may be less in the early removal group - especially if the stent was not exposed to the external environment. The studies identified for this review were generally of poor quality. It is uncertain whether a bladder indwelling ureteric stent that is removed early following kidney transplantation reduces the risk of complications, however it may prevent urine tract infections."
    },
    {
        "index": "cochrane-simplification-test-447",
        "sentence": "We included five studies that evaluated three comparisons. Four studies compared crowns with fillings; two of them compared conventional PMCs with open sandwich restorations, and two compared PMCs fitted using the Hall Technique with fillings. One of these studies included a third arm, which allowed the comparison of PMCs (fitted using the Hall Technique) versus non-restorative caries treatment. In the two studies using crowns fitted using the conventional method, all teeth had undergone pulpotomy prior to the crown being placed. The final study compared two different types of crowns: PMCs versus aesthetic stainless steel crowns with white veneers. No RCT evidence was found that compared different methods of fitting preformed metal crowns (i.e. Hall Technique versus conventional technique). We considered outcomes reported at the dental appointment or within 24 hours of it, and in the short term (less than 12 months) or long term (12 months or more). Some of our outcomes of interest were not measured in the studies: time to restoration failure or retreatment, patient satisfaction and costs. Crowns versus fillings All studies in this comparison used PMCs. One study reported outcomes in the short term and found no reports of major failure or pain in either group. There was moderate quality evidence that the risk of major failure was lower in the crowns group in the long term (risk ratio (RR) 0.18, 95% confidence interval (CI) 0.06 to 0.56; 346 teeth in three studies, one conventional and two using Hall Technique). Similarly, there was moderate quality evidence that the risk of pain was lower in the long term for the crown group (RR 0.15, 95% CI 0.04 to 0.67; 312 teeth in two studies). Discomfort associated with the procedure was lower for crowns fitted using the Hall Technique than for fillings (RR 0.56, 95% CI 0.36 to 0.87; 381 teeth) (moderate quality evidence). It is uncertain whether there is a clinically important difference in the risk of gingival bleeding when using crowns rather than fillings, either in the short term (RR 1.69, 95% CI 0.61 to 4.66; 226 teeth) or long term (RR 1.74, 95% CI 0.99 to 3.06; 195 teeth, two studies using PMCs with conventional technique at 12 months) (low quality evidence). Crowns versus non-restorative caries treatment Only one study compared PMCs (fitted with the Hall Technique) with non-restorative caries treatment; the evidence quality was very low and we are therefore we are uncertain about the estimates. Metal crowns versus aesthetic crowns One split-mouth study (11 participants) compared PMCs versus aesthetic crowns (stainless steel with white veneers). It provided very low quality evidence so no conclusions could be drawn. Crowns placed on primary molar teeth with carious lesions, or following pulp treatment, are likely to reduce the risk of major failure or pain in the long term compared to fillings. Crowns fitted using the Hall Technique may reduce discomfort at the time of treatment compared to fillings. The amount and quality of evidence for crowns compared to non-restorative caries, and for metal compared with aesthetic crowns, is very low. There are no RCTs comparing crowns fitted conventionally versus using the Hall Technique.",
        "gold": "We searched medical and dental sources for studies up to 21 January 2015. We identified five relevant studies. They were at high risk of bias because the participants knew which treatment they received and so did the people who treated them. Four studies compared crowns with fillings. Two of them compared metal crowns fitted using the conventional method with fillings and two compared metal crowns fitted using the Hall Technique with fillings. One of the studies also compared the Hall Technique with 'non-restorative caries treatment' (not using either a filling or crown but opening the cavity to make it possible to clean with a toothbrush, sealing with fluoride varnish and encouraging toothbrushing). The final study compared crowns made of two different materials (stainless steel versus stainless steel with a white covering). We looked at what happened for each treatment at the time of the dental appointment or within 24 hours of treatment, in the short term (less than 12 months) and long term (12 months to 48 months). Teeth restored with preformed crowns are less likely to develop problems (e.g. abscess) or cause pain in the long term, compared to fillings. Crowns fitted using the Hall Technique (no injections or tooth trimming) gave less discomfort at the time of the appointment, when compared with fillings. Crowns may increase the risk of gingival bleeding but this result was unclear. Only one small study compared crowns with non-restorative caries treatment and one small study compared metal and white crowns, and we could draw no reliable conclusions from these. Some of our outcomes of interest were not measured in any of the studies: these included time to restoration failure or retreatment, patient satisfaction and costs. There is moderate quality evidence that crowns are more effective than fillings for managing decay in primary molar teeth. There is moderate quality evidence that crowns fitted using the Hall Technique are less likely to cause abscesses and pain than fillings. The evidence comparing preformed crowns with non-restorative caries management, and comparing preformed metal crowns with preformed white crowns, is very low quality so we do not know which is better. Crowns placed on primary molar teeth with decay, or that have had pulp treatment, are likely to reduce the risk of major failure or pain in the long term compared to fillings. Crowns fitted using the Hall Technique may reduce discomfort at the time of treatment compared to fillings."
    },
    {
        "index": "cochrane-simplification-test-448",
        "sentence": "A total of 28 studies (involving 788 children and adults) were included in the review; 18 studies involving 296 participants were cross-over in design. Data were not published in sufficient detail in most of these studies to perform any meta-analysis. In 22 of the 28 studies the PEP technique was performed using a mask, in three of the studies a mouthpiece was used with nose clips and in three studies it was unclear whether a mask or mouthpiece was used. These studies compared PEP to ACBT, autogenic drainage (AD), oral oscillating PEP devices, high-frequency chest wall oscillation (HFCWO) and BiPaP and exercise. Forced expiratory volume in one second was the review's primary outcome and the most frequently reported outcome in the studies (24 studies, 716 participants). Single interventions or series of treatments that continued for up to three months demonstrated little or no difference in effect between PEP and other methods of airway clearance on this outcome (low- to moderate-quality evidence). However, long-term studies had equivocal or conflicting results regarding the effect on this outcome (low- to moderate-quality evidence). A second primary outcome was the number of respiratory exacerbations. There was a lower exacerbation rate in participants using PEP compared to other techniques when used with a mask for at least one year (five studies, 232 participants; moderate- to high-quality evidence). In one of the included studies which used PEP with a mouthpiece, it was reported (personal communication) that there was no difference in the number of respiratory exacerbations (66 participants, low-quality evidence). Participant preference was reported in 10 studies; and in all studies with an intervention period of at least one month, this was in favour of PEP. The results for the remaining outcome measures (including our third primary outcome of mucus clearance) were not examined or reported in sufficient detail to provide any high-quality evidence; only very low- to moderate-quality evidence was available for other outcomes. There was limited evidence reported on adverse events; these were measured in five studies, two of which found no events. In a study where infants performing either PEP or PDPV experienced some gastro-oesophageal reflux , this was more severe in the PDPV group (26 infants, low-quality evidence). In PEP versus oscillating PEP, adverse events were only reported in the flutter group (five participants complained of dizziness, which improved after further instructions on device use was provided) (22 participants, low-quality evidence). In PEP versus HFCWO, from one long-term high-quality study (107 participants) there was little or no difference in terms of number of adverse events; however, those in the PEP group had fewer adverse events related to the lower airways when compared to HFCWO (high-certainty evidence). Many studies had a risk of bias as they did not report how the randomisation sequence was either generated or concealed. Most studies reported the number of dropouts and also reported on all planned outcome measures. The evidence provided by this review is of variable quality, but suggests that all techniques and devices described may have a place in the clinical treatment of people with CF. Following meta-analyses of the effects of PEP versus other airway clearance techniques on lung function and patient preference, this Cochrane Review demonstrated that there was high-quality evidence that showed a significant reduction in pulmonary exacerbations when PEP using a mask was compared with HFCWO. It is important to note that airway clearance techniques should be individualised throughout life according to developmental stages, patient preferences, pulmonary symptoms and lung function. This also applies as conditions vary between baseline function and pulmonary exacerbations.",
        "gold": "The review includes 28 studies with 788 people (from infants to adults) with CF with mild to severe lung disease. The studies compared PEP to other methods of chest physiotherapy; the length of treatment ranged from a single session to two years of treatment. Generally, the efficacy of PEP is similar to other methods of chest physiotherapy such as postural drainage with percussion, active cycle of breathing techniques, autogenic drainage, oscillatory PEP devices such as the flutter and acapella, thoracic oscillating devices such as the 'Vest', and bilevel positive airway pressure (BiPaP) (typically used for ventilatory support, but by changing the inspiratory and expiratory pressures on the device and combining it with huffing, BiPaP has been used for airway clearance). We found no difference between PEP and other forms of chest physiotherapy in lung function, the amount of mucus cleared from the airways or its related effects on the health of people with CF. However, the rate of flare ups of respiratory symptoms decreased in people using PEP compared to other forms of physiotherapy such as a vibrating PEP device or a vibrating vest. There was some evidence that people with CF may prefer PEP to other chest physiotherapy methods. There was no evidence of PEP causing harm, except in one study where infants performing either PEP or percussion in various positions which use gravity to help drain secretions, experienced some gastro-oesophageal reflux (regurgitation of food) in head-down positions; this was more severe in the group using postural drainage with percussion. In all the other trials PEP was performed in a sitting position. In 10 of the 28 studies studied single PEP treatment sessions. The results from these studies are very limited as they could not report on the number of respiratory infections and lung function did not change with just one treatment. Two one-year studies compared PEP to postural drainage and percussion; in the study with children, PEP improved their lung function, while in the adult study, lung function declined slightly with both PEP and postural drainage and percussion. Also, the method of performing PEP was different in the two age groups. Although PEP seems to have an advantage in reducing flare ups (based on the combined results of a few studies), different physiotherapy techniques and devices may be more or less effective at varying times and in different individuals during baseline function and chest flare ups. Each person should talk to their clinician to help choose which method of airway clearance is best for them and which they will adhere to, so as to provide the best quality of life and long-term outcomes. Some studies were of low quality. These studies highlight the difficulty in comparing studies using PEP compared to other forms of chest physiotherapy. Factors such as age and severity of lung disease in the participants may affect the results as well as the method of performing each treatment. Overall, the evidence provided by this review for whether PEP reduces flare ups compared to other forms of chest physiotherapy was moderate to high quality, but evidence for other outcomes was of very low to moderate quality, as results were limited."
    },
    {
        "index": "cochrane-simplification-test-449",
        "sentence": "Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias. CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively. CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively. In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.",
        "gold": "The literature was searched up to 28 January 2019. Four studies involving 1485 patients compared certolizumab pegol with placebo (a dummy drug). All studies included patients with active Crohn\u2019s disease. Most patients were adults over 18 years of age, except for six patients aged 16 or 17 years old. All studies were funded by the drug manufacturer. In a combined analysis of the four studies, patients with active Crohn\u2019s disease who received certolizumab pegol at a dose ranging from 100 mg to 400 mg every 2 to 4 weeks, responded to the treatment and achieved remission at 8 weeks more often than patients taking placebo. No remarkable difference in the rate of serious side effects was observed between certolizumab pegol and placebo. Serious side effects included worsening Crohn's disease, infections, and malignancy (i.e. cancer). Moderate certainty evidence suggests that certolizumab pegol is beneficial in terms of achieving remission in people with moderate to severe Crohn's disease. Because of a low number of serious side effects, the certainty of evidence about harms of certolizumab pegol was moderate. Moderate certainty evidence suggests that certolizumab pegol is effective for induction of clinical remission and clinical response in people with active Crohn's disease. It is uncertain whether the risk of serious side effects differs between certolizumab pegol and placebo. Future studies are needed to evaluate the long-term benefits and harms of certolizumab pegol in people with Crohn's disease."
    },
    {
        "index": "cochrane-simplification-test-450",
        "sentence": "One hundred and twelve studies met our selection criteria: 15 were studies of adults with CKD; 16 studies were conducted in the general population but provided subgroup data for people with CKD; and 81 studies included individuals with CKD, however, data for this subgroup were not provided. The risk of bias in all 112 studies was frequently high or unclear. Of the 31 studies (23,762 participants) with data on CKD patients, follow-up ranged from three months to five years, and study size ranged from 16 to 2916 participants. In total, 26 studies (19,612 participants) reported disaggregated and extractable data on at least one outcome of interest for our review and were included in our meta-analyses. In acute heart failure, the effects of adenosine A1-receptor antagonists, dopamine, nesiritide, or serelaxin on death, hospitalisations, worsening heart failure or kidney function, hyperkalaemia, hypotension or quality of life were uncertain due to sparse data or were not reported. In chronic heart failure, the effects of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) (4 studies, 5003 participants: RR 0.85, 95% CI 0.70 to 1.02; I2 = 78%; low certainty evidence), aldosterone antagonists (2 studies, 34 participants: RR 0.61 95% CI 0.06 to 6.59; very low certainty evidence), and vasopressin receptor antagonists (RR 1.26, 95% CI 0.55 to 2.89; 2 studies, 1840 participants; low certainty evidence) on death (any cause) were uncertain. Treatment with beta-blockers may reduce the risk of death (any cause) (4 studies, 3136 participants: RR 0.69, 95% CI 0.60 to 0.79; I2 = 0%; moderate certainty evidence). Treatment with ACEi or ARB (2 studies, 1368 participants: RR 0.90, 95% CI 0.43 to 1.90; I2 = 97%; very low certainty evidence) had uncertain effects on hospitalisation for heart failure, as treatment estimates were consistent with either benefit or harm. Treatment with beta-blockers may decrease hospitalisation for heart failure (3 studies, 2287 participants: RR 0.67, 95% CI 0.43 to 1.05; I2 = 87%; low certainty evidence). Aldosterone antagonists may increase the risk of hyperkalaemia compared to placebo or no treatment (3 studies, 826 participants: RR 2.91, 95% CI 2.03 to 4.17; I2 = 0%; low certainty evidence). Renin inhibitors had uncertain risks of hyperkalaemia (2 studies, 142 participants: RR 0.86, 95% CI 0.49 to 1.49; I2 = 0%; very low certainty). We were unable to estimate whether treatment with sinus node inhibitors affects the risk of hyperkalaemia, as there were few studies and meta-analysis was not possible. Hyperkalaemia was not reported for the CKD subgroup in studies investigating other therapies. The effects of ACEi or ARB, or aldosterone antagonists on worsening heart failure or kidney function, hypotension, or quality of life were uncertain due to sparse data or were not reported. Effects of anti-arrhythmic agents, digoxin, phosphodiesterase inhibitors, renin inhibitors, sinus node inhibitors, vasodilators, and vasopressin receptor antagonists were very uncertain due to the paucity of studies. The effects of pharmacological interventions for heart failure in people with CKD are uncertain and there is insufficient evidence to inform clinical practice. Study data for treatment outcomes in patients with heart failure and CKD are sparse despite the potential impact of kidney impairment on the benefits and harms of treatment. Future research aimed at analysing existing data in general population HF studies to explore the effect in subgroups of patients with CKD, considering stage of disease, may yield valuable insights for the management of people with HF and CKD.",
        "gold": "We found 31 studies involving 23,762 people with heart failure and chronic kidney disease. Patients were given either a heart failure medicine compared to standard care or a placebo. The treatment they received was decided by random chance. Although there were many different treatments studied, unfortunately, few of them looked at the same type of medicine. As well, there were many different ways that researchers measured what happened when patients took these medicines. As a result, we could not combine the studies together and clarify the benefits and harms of each treatment. Existing studies cannot really tell us whether medicines used to treat heart failure in the general population are effective or safe for people who have both heart failure and chronic kidney disease. We are not able to recommend which heart failure medicines are best for people with heart failure and chronic kidney disease. We need more information from large clinical studies. Most of the heart failure studies did not report treatment effects separately based on levels of kidney function. Obtaining this information from existing studies may be helpful to learn more about how to treat heart failure in people with chronic kidney disease."
    },
    {
        "index": "cochrane-simplification-test-451",
        "sentence": "Three studies involving a total of 1945 women were included. Overall, risk of bias across the three trials was mixed. No serious complications were reported in the trials and no neonatal or maternal deaths occurred. The neonatal outcome was not statistically different between groups: Apgar score less than seven at five minutes (RR 1.78, 95% CI 0.83 to 3.83; three studies, n = 1945); umbilical artery pH less than 7.15 (RR 1.31, 95% CI 0.95 to 1.79; one study, n = 1456); umbilical artery pH less than 7.16 (RR 1.23, 95% CI 0.39 to 3.92; one study, n = 239); admission to the neonatal intensive care unit (RR 0.34, 95% CI 0.07 to 1.67; two studies, n = 489); and more than 48 hours hospitalisation (RR 0.92, 95% CI 0.71 to 1.20; one study, n = 1456). The pooled risk for instrumental delivery (including caesarean section, ventouse and forceps extraction) was not statistically significantly different (RR 1.05, 95% CI 0.91 to 1.21; three studies, n = 1945). Hyperstimulation was reported in two studies (n = 489), but there was no statistically significant difference between groups (RR 1.21, 95% CI 0.78 to 1.88). This review found no differences between the two types of monitoring (internal or external tocodynamometry) for any of the maternal or neonatal outcomes. Given that this review is based on three studies (N = 1945 women) of moderate quality, there is insufficient evidence to recommend the use of one form of tocodynamometry over another for women where intravenous oxytocin was administered for induction or augmentation of labour.",
        "gold": "The aim of this review was to compare the effectiveness of IT compared with ET. We included three randomised controlled studies (1945 women). The methodological quality of the studies was considered to be moderate. When comparing internal registration of contractions with external registration of contractions during induced or augmented labour, there were no differences in any of the outcomes for mother or child: adverse neonatal outcomes, instrumental deliveries, caesarean section, use of analgesia or time to delivery. No increased risk for infection was reported when an intrauterine catheter was used in these studies. There is insufficient evidence to recommend the use of one form of tocodynamometry over another for women where intravenous oxytocin is administered for induction or augmentation of labour."
    },
    {
        "index": "cochrane-simplification-test-452",
        "sentence": "We included two trials involving 54 participants with CVI. Many of our review outcomes were not reported or reported by only one of the two studies. The intensity of disease signs and symptoms was measured in both studies but using different scales; we were therefore unable to pool the data. One study reported no difference between the exercise and control groups whereas the second reported a reduction in symptoms in the exercise group. In one study, increases in change in ejection fraction compared with baseline (mean difference (MD) 4.88%, 95% confidence interval (CI) 3.16 to 6.60; 30 participants; P < 0.00001), half venous refilling time (MD 4.20 seconds, 95% CI 3.28 to 5.12; 23 participants; P < 0.00001) and total venous refilling time (MD 9.40 seconds, 95% CI 7.77 to 11.03; 23 participants; P < 0.00001) were observed in the exercise group compared with the control group. One study reported no difference between the exercise and control groups with regard to quality of life or ankle range of motion. Although muscle strength assessed by dynamometry at slow speed did not differ between the two groups in this study, variable peak torque at fast speed was lower in the control group than in the exercise group (2.8 \u00b1 0.9 compared with -0.3 \u00b1 0.6, P < 0.03). The incidence of venous leg ulcers, incidence of surgical intervention to treat symptoms related to CVI and exercise capacity were not assessed or reported in either of the included trials. We rated both included studies as at high risk of bias; hence, these data should be interpreted carefully. Due to the small number of studies and small sample size, we were not able to verify indirectness and publication bias. Therefore, we judged the overall quality of evidence as very low according to the GRADE approach. There is currently insufficient evidence available to assess the efficacy of physical exercise in people with CVI. Future research into the effect of physical exercise should consider types of exercise protocols (intensity, frequency and time), sample size, blinding and homogeneity according to the severity of disease.",
        "gold": "This review included two clinical trials, involving a total of 54 participants, that compared directly the effects of physical exercise and a control intervention (evidence current until May 2016). One study reported no difference between the exercise and control groups whereas the second reported a reduction in symptoms in the exercise group. At the end of the study, an improvement in venous blood return was observed in the exercise group compared with the control group. The included studies did not report on new cases of venous leg ulcers. No difference between the exercise and control groups was observed with regard to participants' quality of life, the range of motion of the ankle joint or overall muscle strength. The overall finding of an improvement in venous blood return in the exercise group favours the idea that physical exercise improves blood flow conditions in people with CVI, but we found the risk of bias due to blinding or randomisation to be high for both studies. We therefore consider that there is currently not enough information to determine whether physical exercise is effective in the management of CVI. Quality of the evidence We judged the overall quality of evidence as very low: the two included studies were small (54 participants in total) and were at high risk of bias based on their methods of blinding or randomisation."
    },
    {
        "index": "cochrane-simplification-test-453",
        "sentence": "Seventy-six trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra-articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses. Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.",
        "gold": "To evaluate the efficacy, effectiveness and safety of HA products, in knee OA, we have conducted a systematic review using Cochrane methodology. The analyses support the contention that the HA class of products is superior to placebo. There is considerable between-product, between-variable and time-dependent variability in the clinical response. The clinical effect for some products against placebo on some variables at some time points is in the moderate to large effect size range. In general, sample size restrictions preclude any definitive comment on the safety of the HA class of products, however, within the constraints of the trial designs employed, no major safety issues were detected. The analyses suggest that viscosupplements are comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events, and that HA products have more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA."
    },
    {
        "index": "cochrane-simplification-test-454",
        "sentence": "Ten randomised clinical trials (RCTs) with a total of 4052 participants fulfilled our inclusion criteria and were included in this review. Four RCTs (1881 participants) compared misoprostol with placebo given in addition to conventional uterotonics. Adjunctive use of misoprostol (in the dose of 600 to 1000 mcg) with simultaneous administration of additional uterotonics did not provide additional benefit for our primary outcomes including maternal mortality (risk ratio (RR) 6.16, 95% confidence interval (CI) 0.75 to 50.85), serious maternal morbidity (RR 0.34, 95% CI 0.01 to 8.31), admission to intensive care (RR 0.79, 95% CI 0.30 to 2.11) or hysterectomy (RR 0.93, 95% CI 0.16 to 5.41). Two RCTs (1787 participants) compared 800 mcg sublingual misoprostol versus oxytocin infusion as primary PPH treatment; one trial included women who had received prophylactic uterotonics, and the other did not. Primary outcomes did not differ between the two groups, although women given sublingual misoprostol were more likely to have additional blood loss of at least 1000 mL (RR 2.65, 95% CI 1.04 to 6.75). Misoprostol was associated with a significant increase in vomiting and shivering. Two trials attempted to test the effectiveness of estrogen and tranexamic acid, respectively, but were too small for any meaningful comparisons of pre-specified outcomes. One study compared lower segment compression but was too small to assess impact on primary outcomes. We did not identify any trials evaluating surgical techniques or radiological interventions for women with primary PPH unresponsive to uterotonics and/or haemostatics. Clinical trials included in the current review were not adequately powered to assess impact on the primary outcome measures. Compared with misoprostol, oxytocin infusion is more effective and causes fewer side effects when used as first-line therapy for the treatment of primary PPH. When used after prophylactic uterotonics, misoprostol and oxytocin infusion worked similarly. The review suggests that among women who received oxytocin for the treatment of primary PPH, adjunctive use of misoprostol confers no added benefit. The role of tranexamic acid and compression methods requires further evaluation. Furthermore, future studies should focus on the best way to treat women who fail to respond to uterotonic therapy.",
        "gold": "The review identified 10 randomised controlled trials involving 4052 women. Seven of these trials looked at a drug called misoprostol, which is a prostaglandin and so works by increasing muscle contractions. Overall, the trials suggest that misoprostol does not work as well as oxytocin infusion, and it has more side effects. However, oxytocin needs to be kept in a refrigerator, and so in settings where refrigeration and infusions are not readily available, misoprostol can be used. Other clinical trials looked into using other types of drugs or squeezing the main artery that supplies blood to the woman. The number of women included in these studies was too small for any useful conclusions regarding their effectiveness and safety."
    },
    {
        "index": "cochrane-simplification-test-455",
        "sentence": "Six trials fulfilled entry criteria. The majority of patients in these trials were preterm. Five small trials evaluated short-term cysteine supplementation of cysteine-free PN. One large multicenter RCT evaluated short-term N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants (\u2264 1000 grams). Growth was not significantly affected by cysteine supplementation (1 trial) or by N-acetylcysteine supplementation (1 trial). Nitrogen retention was significantly increased by cysteine supplementation (4 trials) (WMD 31.8 mg/kg/day, 95% confidence interval +8.2, +55.4, n = 95, including 73 preterm infants). Plasma levels of cysteine were significantly increased by cysteine supplementation but not by N-acetylcysteine supplementation. N-acetylcysteine supplementation did not significantly affect the risks of death by 36 postmenstrual weeks, bronchopulmonary dysplasia (BPD), death or BPD, retinopathy of prematurity (ROP), severe ROP, necrotizing enterocolitis requiring surgery, periventricular leukomalacia, intraventricular hemorrhage (IVH), or severe IVH. Available evidence from RCTs shows that routine short-term cysteine chloride supplementation of cysteine-free PN in preterm infants improves nitrogen balance. However, there is insufficient evidence to assess the risks of cysteine supplementation, especially regarding metabolic acidosis, which has been reported during the first two weeks of cysteine chloride administration. Available evidence from a large RCT trial does not support routine N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants.",
        "gold": "This systemic review was done to analyze whether adding cysteine (or related compounds) to intravenous nutrition affects growth and other outcomes in newborn infants. Five trials studied the effects of adding cysteine to intravenous nutrition that did not contain cysteine. Addition of cysteine significantly improved the babies' ability to build body proteins (analyzed in four studies); however, it did not improve growth (analyzed in one study); no other outcomes were available. One large randomized trial studied the effect of adding another chemical, N-acetyl-cysteine, to intravenous nutrition that already contained cysteine. This study showed no benefit and no toxicity of this intervention. We conclude that present data are insufficient to justify routine addition of cysteine to the intravenous nutrition of newborn infants that does not contain cysteine. Available evidence does not support routine addition of N-acetylcysteine to intravenous nutrition of newborn infants containing cysteine."
    },
    {
        "index": "cochrane-simplification-test-456",
        "sentence": "We identified 77 trials including 6287 participants that met the inclusion criteria of this review. Forty-one trials (3829 participants) provided information for one or more outcomes. Only one trial was at low risk of bias in all domains. All other trials were at high risk of bias in one or more domains. Overall, all the evidence was very low quality. Thirty-five trials included only participants with non-alcohol related steatohepatitis (NASH) (based on biopsy confirmation). Five trials included only participants with diabetes mellitus; 14 trials included only participants without diabetes mellitus. The follow-up in the trials ranged from one month to 24 months. We present here only the comparisons of active intervention versus no intervention in which two or more trials reported at least one of the following outcomes: mortality at maximal follow-up, serious adverse events, and health-related quality of life, the outcomes that determine whether a treatment should be used. Antioxidants versus no intervention There was no mortality in either group (87 participants; 1 trial; very low quality evidence). None of the participants developed serious adverse events in the trial which reported the proportion of people with serious adverse events (87 participants; 1 trial; very low quality evidence). There was no evidence of difference in the number of serious adverse events between antioxidants and no intervention (rate ratio 0.89, 95% CI 0.36 to 2.19; 254 participants; 2 trials; very low quality evidence). None of the trials reported health-related quality of life. Bile acids versus no intervention There was no evidence of difference in mortality at maximal follow-up (OR 5.11, 95% CI 0.24 to 107.34; 659 participants; 4 trials; very low quality evidence), proportion of people with serious adverse events (OR 1.56, 95% CI 0.84 to 2.88; 404 participants; 3 trials; very low quality evidence), or the number of serious adverse events (rate ratio 1.01, 95% CI 0.66 to 1.54; 404 participants; 3 trials; very low quality evidence) between bile acids and no intervention. None of the trials reported health-related quality of life. Thiazolidinediones versus no intervention There was no mortality in either group (74 participants; 1 trial; very low quality evidence). None of the participants developed serious adverse events in the two trials which reported the proportion of people with serious adverse events (194 participants; 2 trials; very low quality evidence). There was no evidence of difference in the number of serious adverse events between thiazolidinediones and no intervention (rate ratio 0.25, 95% CI 0.06 to 1.05; 357 participants; 3 trials; very low quality evidence). None of the trials reported health-related quality of life. Source of funding Twenty-six trials were partially- or fully-funded by pharmaceutical companies that would benefit, based on the results of the trial. Twelve trials did not receive any additional funding or were funded by parties with no vested interest in the results. The source of funding was not provided in 39 trials. Due to the very low quality evidence, we are very uncertain about the effectiveness of pharmacological treatments for people with NAFLD including those with steatohepatitis. Further well-designed randomised clinical trials with sufficiently large sample sizes are necessary.",
        "gold": "We included 77 randomised clinical trials that involved a total of 6287 participants. Of these, 41 trials (3829 participants) provided information for one or more outcomes for this review. Thirty-five trials only included participants with NASH; five included only people with diabetes mellitus; and 14 included only people who did not have diabetes mellitus. The average follow-up period in the trials ranged from one month to two years in the trials that reported this information. We excluded trials in which participants with NAFLD had undergone liver transplantation before the trial. As well as conducting standard Cochrane analysis, we also planned to conduct network meta-analysis (a technique that enables comparison of different treatments that are not directly compared to each other in the trials). However, the nature of available information meant we could not determine if the network meta-analysis results were reliable. Specific outcomes we looked for were numbers of deaths, adverse events, and assessment of health-related quality of life. Twelve trials did not receive any additional funding or were funded by sources with no vested interest in the results; 26 were funded by drug companies that could potentially benefit from trial results; and the funding source was not available from 39 trials. Included trials compared drug treatments such as bile acids, antioxidants, phosphodiesterase type 4 inhibitor, glucocorticosteroid inhibitor, anti-cholesterol drugs and anti-diabetes drugs with a fake treatment (placebo) or no treatment. There were no deaths in either group (87 participants, 1 trial). None of the participants developed serious adverse events in the trial which reported the percentage of people with serious adverse events (87 participants, 1 trial). There was no evidence of difference in the number of serious adverse events between antioxidants and no intervention (254 participants, 2 trials). There was no evidence of difference in deaths at maximal follow-up (659 participants, 4 trials), percentage of people with serious adverse events (404 participants, 3 trials), or the number of serious adverse events (404 participants, 3 trials) between bile acids and no intervention. None of the trials reported health-related quality of life. There were no deaths in either group (74 participants, 1 trial). None of the participants developed serious adverse events in the two trials which reported the percentage of people with serious adverse events (194 participants, 2 trials). There was no evidence of difference in the number of serious adverse events between thiazolidinediones and no intervention (357 participants, 3 trials). None of the trials reported health-related quality of life. We found no evidence of benefit from any of the compared interventions in people with fatty liver disease. There is significant uncertainty in this issue, and we need further high quality randomised clinical trials with sufficiently large group of participants. Evidence quality was very low overall, and there was a high risk of bias. This means there is a possibility of making conclusions that wrongly interpret benefits or harms of treatments because of the ways the studies were conducted."
    },
    {
        "index": "cochrane-simplification-test-457",
        "sentence": "In total, 1282 participants with MCI at baseline were identified in the 15 included studies of which 1172 had analysable data; 430 participants converted to Alzheimer\u2019s disease dementia and 130 participants to other forms of dementia. Follow-up ranged from less than one year to over four years for some participants, but in the majority of studies was in the range one to three years. Conversion to Alzheimer\u2019s disease dementia The accuracy of the CSF t-tau was evaluated in seven studies (291 cases and 418 non-cases).The sensitivity values ranged from 51% to 90% while the specificity values ranged from 48% to 88%. At the median specificity of 72%, the estimated sensitivity was 75% (95% CI 67 to 85), the positive likelihood ratio was 2.72 (95% CI 2.43 to 3.04), and the negative likelihood ratio was 0.32 (95% CI 0.22 to 0.47). Six studies (164 cases and 328 non-cases) evaluated the accuracy of the CSF p-tau. The sensitivities were between 40% and 100% while the specificities were between 22% and 86%. At the median specificity of 47.5%, the estimated sensitivity was 81% (95% CI: 64 to 91), the positive likelihood ratio was 1.55 (CI 1.31 to 1.84), and the negative likelihood ratio was 0.39 (CI: 0.19 to 0.82). Five studies (140 cases and 293 non-cases) evaluated the accuracy of the CSF p-tau/ABeta ratio. The sensitivities were between 80% and 96% while the specificities were between 33% and 95%. We did not conduct a meta-analysis because the studies were few and small. Only one study reported the accuracy of CSF t-tau/ABeta ratio. Our findings are based on studies with poor reporting. A significant number of studies had unclear risk of bias for the reference standard, participant selection and flow and timing domains. According to the assessment of index test domain, eight of 15 studies were of poor methodological quality. The accuracy of these CSF biomarkers for \u2018other dementias\u2019 had not been investigated in the included primary studies. Investigation of heterogeneity The main sources of heterogeneity were thought likely to be reference standards used for the target disorders, sources of recruitment, participant sampling, index test methodology and aspects of study quality (particularly, inadequate blinding). We were not able to formally assess the effect of each potential source of heterogeneity as planned, due to the small number of studies available to be included. The insufficiency and heterogeneity of research to date primarily leads to a state of uncertainty regarding the value of CSF testing of t-tau, p-tau or p-tau/ABeta ratio for the diagnosis of Alzheimer's disease in current clinical practice. Particular attention should be paid to the risk of misdiagnosis and overdiagnosis of dementia (and therefore over-treatment) in clinical practice. These tests, like other biomarker tests which have been subject to Cochrane DTA reviews, appear to have better sensitivity than specificity and therefore might have greater utility in ruling out Alzheimer's disease as the aetiology to the individual's evident cognitive impairment, as opposed to ruling it in. The heterogeneity observed in the few studies awaiting classification suggests our initial summary will remain valid. However, these tests may have limited clinical value until uncertainties have been addressed. Future studies with more uniformed approaches to thresholds, analysis and study conduct may provide a more homogenous estimate than the one that has been available from the included studies we have identified.",
        "gold": "The evidence is current to January 2013. We included 15 studies containing a total of 1282 participants with MCI. The majority of studies (n = 9) were published between 2010 and 2013. The remaining six studies were published between 2004 and 2009. All of the included studies were conducted in Europe. Study sizes varied and ranged from 15 to 231 participants.The mean (range) age of the youngest sample was 64 years (45 to 76) and the mean (standard deviation) age of the oldest sample was 73.4 (6.6) years. Our findings are based on studies with poor reporting, with a majority of studies at unclear risk of bias due to insufficient details given on how participants were selected and how the clinical diagnosis of dementia was established. According to the assessment of how the CSF tests were conducted and analysed, eight of 15 studies were of poor methodological quality. Below is a summary of key findings for the tests: CSF t-tau test for conversion from MCI to Alzheimer\u2019s disease dementia The sensitivity values in seven individual studies ranged from 51% to 90% while the specificity values ranged from 48% to 88%. The statistical analysis of those studies showed that, at the fixed specificity of 72%, the estimated sensitivity was 77%, and, at the prevalence of 37%, the positive predictive value was 62% and the negative predictive value was 84%. Based on these results, on average 62 out of 100 people with MCI and a positive index test result would convert to Alzheimer's disease dementia but 38 would not; on average, 84 out of 100 people with MCI and with a negative index test result would not convert to Alzheimer's disease dementia, but 16 would. CSF p-tau test for conversion from MCI to Alzheimer\u2019s disease dementia The sensitivity values in six individual studies ranged from 40% to 100% while the specificity values ranged from 22% to 86%. The statistical analysis of those studies showed that, at the fixed specificity of 48%, the estimated sensitivity was 81%, and, at the prevalence of 37%, the positive predictive value was 48% and the negative predictive value was 81%. Based on these results, on average 48 out of 100 people with MCI and with a positive index test result would convert to Alzheimer's disease dementia, but 52 would not; on average, 81 out of 100 people with MCI with a negative index test result would not convert to Alzheimer's disease dementia, but 19 would. We found that the cerebrospinal fluid (CSF) diagnostic test, as a single test, lacks the accuracy to identify those people with mild cognitive impairment (MCI) who would develop Alzheimer\u2019s disease dementia or other forms of dementia over a period of time. The data suggested that a negative CSF test, in people with MCI, almost indicates the absence of Alzheimer's disease as the cause of their clinical symptoms. However, a positive CSF test does not confirm the presence of Alzheimer's disease as the aetiology (cause) of their clinical symptoms. There were methodological problems in the included studies that did not allow for a clear answer to the review question. The main limitations of the review were poor reporting in the included studies, lack of a widely accepted threshold of the CSF diagnostic tests in people with MCI, variability in length of follow-up, and the marked variation in CSF tests\u2019 accuracy between the included studies."
    },
    {
        "index": "cochrane-simplification-test-458",
        "sentence": "We included three single-centre, two-arm RCTs involving 170 participants. We found one ongoing trial. All included participants were male and were undergoing radical robotic assisted laparoscopic radical prostatectomy (RALRP). The men were between 50 and 75 years of age and met criteria for American Society of Anesthesiologists physical classification scores (ASA) I, ll and III. We found evidence showing no clinically meaningful differences in postoperative pain between the two types of anaesthetics (mean difference (MD) in visual analogue scale (VAS) scores at one to six hours was -2.20 (95% confidence interval (CI) -10.62 to 6.22; P = 0.61) in a sample of 62 participants from one study. Low-quality evidence suggests that propofol reduces postoperative nausea and vomiting (PONV) over the short term (one to six hours after surgery) after RALRP compared with inhalational anaesthesia (sevoflurane, desflurane) (MD -1.70, 95% CI -2.59 to -0.81; P = 0.0002). We found low-quality evidence suggesting that propofol may prevent an increase in intraocular pressure (IOP) after pneumoperitoneum and steep Trendelenburg positioning compared with sevoflurane (MD -3.90, 95% CI -6.34 to -1.46; P = 0.002) with increased IOP from baseline to 30 minutes in steep Trendelenburg. However, it is unclear whether this surrogate outcome translates directly to clinical avoidance of ocular complications during surgery. No studies addressed the secondary outcomes of adverse effects, all-cause mortality, respiratory or circulatory complications, cognitive dysfunction, length of stay or costs. Overall the quality of evidence was low to very low, as all studies were small, single-centre trials providing unclear descriptions of methods. It is unclear which anaesthetic technique is superior - TIVA or inhalational - for transabdominal robotic assisted surgery in urology, gynaecology and gastroenterology, as existing evidence is scarce, is of low quality and has been generated from exclusively male patients undergoing robotic radical prostatectomy. An ongoing trial, which includes participants of both genders with a focus on quality of recovery, might have an impact on future evidence related to this topic.",
        "gold": "The evidence is current to May 2016 and was provided by three small randomized controlled trials involving 170 males who had their prostate removed. These studies took place in hospitals in Korea and Turkey. We looked for differences in pain and postoperative nausea and vomiting (PONV) and changes in pressure inside the eyes between patients receiving anaesthetic via the veins or by inhalation. Study funding sources Studies were funded by the institution, or the funding sources were not stated. Key results Postoperative pain was no different between the two types of anaesthesia. Anaesthesia delivered through the veins reduced PONV at one to six hours after prostate surgery compared with anaesthesia provided via inhalation. One study showed that anaesthesia delivered through the veins prevented an increase in pressure inside the eyes during surgery compared with inhalational anaesthesia. We cannot conclude whether this means that anaesthesia provided via the veins reduces ocular complications, as no patients in this small study developed these complications. Quality of the evidence The quality of the evidence was considered low, as included studies were small and provided an unclear description of methods. All participants in these studies were men who were undergoing robotic assisted laparoscopic removal of the prostate. An ongoing trial includes men and women undergoing abdominal robotic surgery, also with a focus on the quality of recovery. Additional studies are needed."
    },
    {
        "index": "cochrane-simplification-test-459",
        "sentence": "We included 7 new observational studies in this update, bringing the total number to 14, including 5 cohort and 9 case-control studies, with 1,601,515 study subjects. Most studies found no causal associations between maternal exposure to topical corticosteroids of any potency and pregnancy outcomes when compared with no exposure. These outcomes included: mode of delivery (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.15, 1 cohort study, n = 9904, low quality evidence); congenital abnormalities, including orofacial cleft or cleft palate and hypospadias (where the urethral opening is on the underside of the penis) (RR 0.82, 95% CI 0.34 to 1.96, 2 cohort studies, n = 9512, low quality evidence; and odds ratio (OR) 1.07, 95% CI 0.71 to 1.60, 1 case-control study, n = 56,557); low birth weight (RR 1.08, 95% CI 0.86 to 1.36; n = 59,419, 4 cohort studies; very low quality evidence); preterm delivery (RR 0.93, 95% CI 0.81 to 1.08, 4 cohort studies, n = 59,419, low quality evidence); foetal death (RR 1.02, 95% CI 0.60 to 1.73, 4 cohort studies, n = 63,885, very low quality evidence); and low Apgar score (RR 0.84, 95% CI 0.54 to 1.31, 1 cohort study, n = 9220, low quality evidence). We conducted stratified analyses of mild or moderate potency, and potent or very potent topical corticosteroids, but we found no causal associations between maternal exposure to topical corticosteroid of any potency and congenital abnormality, orofacial clefts, preterm delivery, or low Apgar score. For low birth weight, although the meta-analysis based on study-level data was not significant for either mild to moderate corticosteroids (pooled RR 0.90, 95% CI 0.74 to 1.09, 3 cohort studies, n > 55,713) or potent to very potent corticosteroids (pooled RR 1.58, 95% CI 0.96 to 2.58, 4 cohort studies, n > 47,651), there were significant differences between the two subgroups (P = 0.04). The results from three of the individual studies in the meta-analysis indicated an increased risk of low birth weight in women who received potent to very potent topical corticosteroids. Maternal use of mild to moderate potency topical steroids was associated with a decreased risk of foetal death (pooled RR 0.70, 95% CI 0.64 to 0.77, 2 studies, n = 48,749; low quality evidence), but we did not observe this effect when potent to very potent topical corticosteroids were given during pregnancy (pooled RR 1.14, 95% CI 0.69 to 1.88, 3 studies, n = 37,086, low quality evidence). We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group approach to rate the overall quality of the evidence. Data from observational studies started at low quality. We further downgraded the evidence because of imprecision in low birth weight and inconsistency in foetal death. Lower quality evidence resulted in lower confidence in the estimate of effect for those outcomes. This update adds more evidence showing no causal associations between maternal exposure to topical corticosteroids of all potencies and pregnancy outcomes including mode of delivery, congenital abnormalities, preterm delivery, foetal death, and low Apgar score, which is consistent with the previous version of this review. This update provides stratified analyses based on steroid potency; we found no association between maternal use of topical corticosteroids of any potency and an increase in adverse pregnancy outcomes, including mode of delivery, congenital abnormality, preterm delivery, foetal death, and low Apgar score. Similar to the previous version of the review, this update identified a probable association between low birth weight and maternal use of potent to very potent topical corticosteroids, especially when the cumulative dosage of topical corticosteroids throughout the pregnancy is very large, which warrants further investigation. The finding of a possible protective effect of mild to moderate topical corticosteroids on foetal death could also be examined.",
        "gold": "We updated the review that was previously published in 2009. We examined the research published up to July 2015 and found seven new studies. All in all, this updated review included a total of 14 observational studies that assessed 1,601,515 pregnancies. Observational studies are generally regarded as less rigorous than randomised controlled clinical trials. The funding source was from academic or governmental institutions in 10 studies and was not reported in 4 studies. We found no associations between mothers' use of topical steroids of any potency and type of delivery, birth defects, premature births, or low Apgar score. There is some evidence indicating a relation between low birth weight and maternal use of potent or very potent topical steroids, especially when high doses are used in pregnancy, and this may warrant more research. On the other hand, maternal use of mild or moderate topical corticosteroids is not related to low birth weight. We even found that mild or moderately potent topical steroids protect against death of the baby, but this was not seen when the mothers used potent or very potent topical steroids. This finding needs further examination. The overall quality of evidence is low because all available studies were observational. The high quality study design of the randomised controlled trial that allocates participants to receive either topical corticosteroids or no treatment is not generally feasible in pregnant women due to ethical concerns about possible exposure of the foetus to an experimental treatment. Where we further downgraded the quality of the evidence to 'very low', it was because we had detected variation in the results from the studies that we found, which means that we have low confidence in our estimates of the effects for our outcomes."
    },
    {
        "index": "cochrane-simplification-test-460",
        "sentence": "We found four RCTs that met the inclusion criteria of this review. The total number of included participants was 611 (612 eyes), ranging from 30 to 500 participants per trial. One trial was included in the previous version of the review, and we identified three additional trials through the updated searches in July 2014. One of the three smaller trials was a pilot study of the largest study: the Steroids for Corneal Ulcers Trial (SCUT). All trials compared the treatment of bacterial keratitis with topical corticosteroid and without topical corticosteroid and had follow-up periods ranging from two months to one year. These trials were conducted in the USA, Canada, India, and South Africa. All trials reported data on visual acuity ranging from three weeks to one year, and none of them found any important difference between the corticosteroid group and the control group. The pilot study of the SCUT reported that time to re-epithelialization in the steroid group was 53% slower than the placebo group after adjusting for baseline epithelial defect size (hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.23 to 0.94). However, the SCUT did not find any important difference in time to re-epithelialization (HR 0.92; 95% CI 0.76 to 1.11). For adverse events, none of the three small trials found any important difference between the two treatment groups. The investigators of the largest trial reported that more patients in the control group developed intraocular pressure (IOP) elevation (risk ratio (RR) 0.20; 95% CI 0.04 to 0.90). One trial reported quality of life and concluded that there was no difference between the two groups (data not available). We did not find any reports regarding economic outcomes. Although the four trials were generally of good methodological design, all trials had considerable losses to follow-up (10% or more) in the final analyses. Further, three of the four trials were underpowered to detect treatment effect differences between groups and inconsistency in outcome measurements precluded meta-analyses for most outcomes relevant to this review. There is inadequate evidence as to the effectiveness and safety of adjunctive topical corticosteroids compared with no topical corticosteroids in improving visual acuity, infiltrate/scar size, or adverse events among participants with bacterial keratitis. Current evidence does not support a strong effect of corticosteroid, but may be due to insufficient power to detect a treatment effect.",
        "gold": "We found four studies in which antibiotics alone had been compared with antibiotics plus corticosteroids for the treatment of bacterial keratitis. These studies were conducted in the USA, Canada, India, and South Africa, and included a total of 612 eyes of 611 participants. The largest study included 500 participants followed for one year. The three smaller studies followed participants for two to three months. The evidence is current to July 2014. None of the four studies reported an important difference between topical corticosteroid therapy and placebo or control treatment for reduction in ulcer size, change in visual acuity, adverse events, or quality of life. One study reported that healing or cure time in the steroid group was slower than the placebo group (for every 100 people cured in the control group, only 47 were cured in the steroid group during the same time period), but the largest study did not report any difference (for every 100 people cured in the control group, 92 were cured in the steroid group during the same time interval). For adverse events, none of the studies found a difference between the two groups, except that one study reported that more eyes in the control group developed intraocular pressure (IOP) elevation. We did not find any information on economic outcomes. Generally, the quality of the evidence based on the four studies we identified was moderate due to the proportions of participants who were not included in the final study analyses and the inconsistency of outcomes assessed across the four studies. In addition, three studies enrolled too few participants (30 to 42) to reach scientifically valid conclusions."
    },
    {
        "index": "cochrane-simplification-test-461",
        "sentence": "We included four trials with 450 participants. Data on functional outcome and death at end of follow-up were available for 443 participants from three trials. Compared with intravenous thrombolytic therapy, percutaneous vascular intervention did not improve the proportion of participants with good functional outcome (modified Rankin Scale score 0 to 2, risk ratio (RR) 1.01, 95% confidence interval (CI) 0.82 to 1.25, P = 0.92). The quality of evidence was low (outcome assessment was blinded, but not the treating physician or participants). At the end of follow-up, there was a non-significant increase in the proportion of participants who died in the percutaneous vascular intervention group (RR 1.34, 95% CI 0.84 to 2.14, P = 0.21). The quality of evidence was low (wide confidence interval). There was no difference in the proportion of participants with symptomatic intracranial haemorrhages between the intervention and control groups (RR 0.99, 95% CI 0.50 to 1.95, P = 0.97). The quality of evidence was low (wide confidence interval). Data on vascular status (recanalisation rate) were only available for seven participants from one trial; we considered this inadequate for statistical analyses. The present review directly compared intravenous thrombolytic treatment with percutaneous vascular interventions for ischaemic stroke. We found no evidence from RCTs that percutaneous vascular interventions are superior to intravenous thrombolytic treatment with respect to functional outcome. Quality of evidence was low (outcome assessment was blinded, but not the treating physician or participants). New trials with adequate sample sizes are warranted because of the rapid development of new techniques and devices for such interventions.",
        "gold": "We included four trials with 450 participants randomised to either percutaneous vascular intervention or clot-dissolving drugs given by injection. The evidence is current as of September 2017. Compared with clot-dissolving drugs, percutaneous vascular interventions did not increase the chance of making a good recovery by the end of the trial. There was no significant increase in the risk of dying or of suffering a brain bleed. New, larger trials are needed, particularly because of the rapid development of new techniques and devices for percutaneous vascular interventions. We judged the quality of the evidence to be low because of the limited amount of trial information available."
    },
    {
        "index": "cochrane-simplification-test-462",
        "sentence": "We included in the review one trial, involving 120 families and 143 children. Risk of bias was high because of contamination between groups, as 63% of control group participants accessed day care services separate from those offered within the intervention. No evidence suggested that centre-based day care, rather than no treatment (care at home), improved or worsened children's cognitive ability (Griffiths Mental Development Scale, standardised mean difference (SMD) 0.34, 95% confidence interval (CI) -0.01 to 0.69, 127 participants, 1 study, very low-quality evidence) or psychosocial development (parental report of abnormal development, risk ratio (RR) 1.21, 95% CI 0.25 to 5.78, 137 participants, 1 study, very low-quality evidence). No other measures of child intellectual or psychosocial development were reported in the included study. Moreover, no evidence indicated that centre-based day care, rather than no treatment (care at home), improved or worsened employment of parents, as measured by the number of mothers in full-time or part-time employment (RR 1.12, 95% CI 0.85 to 1.48, 114 participants, 1 study, very low-quality evidence) and maternal hours per week in paid employment (SMD 0.20, 95% -0.15 to 0.55, 127 participants, 1 study, very low-quality evidence) or household income above \u00a3200 per week (RR 0.86, 95% CI 0.57 to 1.29, 113 participants, 1 study, very low-quality evidence). This study did not report on long-term outcomes for children (high-school completion or income). This review includes one trial that provides inconclusive evidence as regards the effects of centre-based day care for children younger than five years of age and their families in high-income countries. Robust guidance for parents, policymakers and other stakeholders on the effects of day care cannot currently be offered on the basis of evidence from randomised controlled trials. Some trials included co-interventions that are unlikely to be found in normal day care centres. Effectiveness studies of centre-based day care without these co-interventions are few, and the need for such studies is significant. Comparisons might include home visits or alternative day care arrangements that provide special attention to children from low-income families while exploring possible mechanisms of effect.",
        "gold": "We included studies that assessed the effects of centre-based day care for children younger than five years of age in high-income countries. To isolate the effects of day care, we excluded interventions that involved medical, psychological or non\u2013child-focused co-interventions. Electronic searches identified 34,890 citations that were screened for inclusion in the review. Only one study (120 families, 143 children), based in London, England, matched all inclusion criteria and was included in the review. Evidence is current to April 2014. Currently very limited evidence is available on the effects of centre-based day care on the cognitive and psychosocial development of children, parental employment or household income, or on long-term outcomes for children. Only one randomised controlled trial (RCT) was included in this review. In addition, a large proportion of families in the non-intervention group secured day care services for themselves. The quality of the evidence included in this review is very low, so the results must be interpreted with caution. Although RCTs do not allow conclusive judgements as regards the role of centre-based day care in the development of children and the economic situation of parents, this does not imply that these services are not important in high-income countries. The need for effectiveness studies of centre-based day care without co-interventions is significant. This review is one of a pair of reviews; researchers and practitioners may find evidence from the low- and middle-income country review to be informative also (Brown 2014)."
    },
    {
        "index": "cochrane-simplification-test-463",
        "sentence": "In total, 126 reports describing 30 scoring indices were identified through the screening process. Eleven of the 30 scoring indices have undergone some form of index validation. Intra-rater reliability was assessed for eight scoring indices. Inter-rater reliability was evaluated for all 11 of the scoring indices. Three of the indices underwent content validation. Two of the included scoring indices assessed criterion validity. Six of the included scoring indices explored content validity. Two of the included scoring indices were tested for responsiveness. The Nancy Index and the Robarts Histopathology Index have undergone the most validation in that four operating properties including reliability, content validity, construct validity (hypothesis testing) and criterion validity have been tested. However, none of the currently available histologic scoring indices have been fully validated. In order to determine the optimal endpoint for histologic healing in UC, more research is required. The optimal index would need to be fully validated.",
        "gold": "The researchers found that 11 out of the 30 histologic scoring indices that exist have been partially validated. The Nancy Index and the Robarts Histopathology Index have undergone the most validation compared to the other nine indices. However, none of the currently available histologic scoring indices have been fully validated. In order to determine the ideal index to measure histologic healing in UC, more research is required. The ideal index would need to be fully validated."
    },
    {
        "index": "cochrane-simplification-test-464",
        "sentence": "We included three randomised trials that evaluated intramedullary nailing versus plating in 213 participants, with useable data from 173 participants of whom 112 were male. The mean age of participants in individual studies ranged from 41 to 44 years. There were no trials comparing surgery with non-surgical treatment. The three included trials were at high risk of performance bias, with one trial also being at high risk of selection, detection and attrition bias. Overall, the quality of available evidence was rated as very low for all outcomes, meaning that we are very unsure about the estimates for all outcomes. Although the pooled results of three different measures of foot and ankle function indicated a small difference in favour of nailing (standard mean difference 0.28, 95% CI -0.02 to 0.59; 172 participants, 3 trials), the results of individual trials indicated that this was very unlikely to be a clinically important difference. Pooled data (173 participants, 3 trials) for the need for reoperation or substantive physiotherapy for adverse events favoured nailing (4/90 versus 10/83; RR 0.37, 95% CI 0.12 to 1.12), but included the possibility of a better outcome after plating. Based on an illustrative risk of 100 re-operations for adverse outcomes within one year of plate fixation in 1000 people with these fractures, 63 fewer (95% CI 88 fewer to 12 more) people per 1000 would have re-operations after nailing. Similarly pooled data (173 participants, 3 trials) for the symptomatic nonunion or malunion, wound complications and fracture union favoured nailing but the 95% confidence intervals crossed the line of no effect and thus included the possibility of a better outcome after plating. Evidence from one trial (85 participants) showed no clinically important difference in pain between the two groups. Overall, there is either no or insufficient evidence to draw definitive conclusions on the use of surgery or the best surgical intervention for distal tibial metaphyseal fractures in adults. The available evidence, which is of very low quality, found no clinically important differences in function or pain, and did not confirm a difference in the need for re-operation or risk of complications between nailing and plating. The addition of evidence from two ongoing trials of nailing versus plating should inform this question in future updates. Further randomised trials are warranted on other issues, but should be preceded by research to identify priority questions.",
        "gold": "We searched medical databases and trials registries in December 2014. We wanted to include studies in which receiving one surgical treatment or another surgical treatment was decided by chance. This research method, termed a randomised controlled trial (RCT), is the best way to ensure that any measured improvement is caused by the treatment itself and no other factors. We found three RCTs involving 213 adults (with results available from 173) that compared nailing versus plating for treating distal tibial fractures. Overall the studies included around twice as many males as females and the average age of the study participants was just over 40 years. We found no trials comparing surgery with non-surgical treatment. We found no clear differences between the nailing and plating groups in terms of patient-reported functional outcomes, re-operations for adverse outcomes, troublesome non-healing of the bone or deformity, pain, wound problems such as infection, or the numbers of individuals with healed fractures. Only three trials were identified and the sample sizes were small, so the results are imprecise. Moreover, the results of one trial were very likely to be biased due to flawed methodology. We therefore judged the overall quality of evidence to be very low, which means that we are very unsure of these results. Overall, the evidence is of very low quality and is insufficient to draw definite conclusions about the best method of surgery, including nailing versus plating, for treating breaks of the lower end of the shin bone in adults. Future updates of this review are likely to include evidence from currently ongoing research comparing nailing versus plating. Although other RCTs are needed to address key clinical questions on surgical methods for treating these fractures, these studies should be preceded by research to determine which questions should be prioritised."
    },
    {
        "index": "cochrane-simplification-test-465",
        "sentence": "We included 11 studies involving a total of 38,742 participants: eight studies compared BPLDs versus placebo or no treatment (35,110 participants), and three studies compared different systolic blood pressure targets (3632 participants). The risk of bias varied greatly between included studies. The pooled risk ratio (RR) of BPLDs for recurrent stroke was 0.81 (95% confidence interval (CI) 0.70 to 0.93; 8 RCTs; 35,110 participants; moderate-quality evidence), for major vascular event 0.90 (95% CI 0.78 to 1.04; 4 RCTs; 28,630 participants; high-quality evidence), and for dementia 0.88 (95% CI 0.73 to 1.06; 2 RCTs; 6671 participants; high-quality evidence). We mainly observed a reduced risk of recurrent stroke in the subgroup of participants using an angiotensin-converting enzyme (ACE) inhibitor or a diuretic (I2 statistic for subgroup differences 72.1%; P = 0.006). The pooled RR of intensive blood pressure-lowering for recurrent stroke was 0.80 (95% CI 0.63 to 1.00), and for major vascular event 0.58 (95% CI 0.23 to 1.46). Our results support the use of BPLDs in people with stroke or TIA for reducing the risk of recurrent stroke. Current evidence is primarily derived from trials studying an ACE inhibitor or a diuretic. No definite conclusions can be drawn from current evidence regarding an optimal systolic blood pressure target after stroke or TIA.",
        "gold": "this review is up-to-date to August 2017. We included 11 trials involving 38,742 participants: eight trials assessed the effect of blood pressure drugs, and three trials compared different blood pressure targets. Ten studies were hospital-based and one trial was performed in a general practitioner setting. Not all trials contributed information to all outcomes. blood pressure drugs lowered the risk of recurrent stroke in patients with a stroke or TIA, whereas there is insufficient evidence to conclude whether they reduce the risk of other blood vessel diseases and dementia. There is also insufficient evidence to conclude which blood pressure target is best for patients with a stroke or TIA. overall, the quality of the trials in this review was moderate. However, we found similar results in an analysis using only high-quality trials. More research is needed to investigate whether blood pressure drugs also prevent dementia, and what blood pressure targets are best for patients with a stroke or TIA."
    },
    {
        "index": "cochrane-simplification-test-466",
        "sentence": "Five hundred nineteen men from four randomized, placebo-controlled, double-blind trials, (lasting 4 to 26 weeks) were assessed. Three trials used non-glucosidic B-sitosterols and one utilized a preparation that contained 100% B-sitosteryl-B-D-glucoside. B-Sitosterols improved urinary symptom scores and flow measures. The weighted mean difference (WMD) for the IPSS was -4.9 IPSS points (95% CI = -6.3 to -3.5, n = 2 studies). The WMD for peak urine flow was 3.91 mL/s (95% CI = 0.91 to 6.90, n = 4 studies) and the WMD for residual volume was -28.62 mL (95% CI = -41.42 to -15.83, n = 4 studies). The trial using 100% B-sitosteryl-B-D-glucoside (WA184) show improvement in urinary flow measures. B-sitosterols did not significantly reduce prostate size compared to placebo. Withdrawal rates for men assigned to B-sitosterol and placebo were 7.8% and 8.0%, respectively. The evidence suggests non-glucosidic B-sitosterols improve urinary symptoms and flow measures. Their long term effectiveness, safety and ability to prevent BPH complications are not known.",
        "gold": "The review found that beta-sitosterol treatments were well tolerated and improved urinary symptoms and flow measures in men with mild to moderate BPH. More research into long-term effects of beta-sitosterols is needed."
    },
    {
        "index": "cochrane-simplification-test-467",
        "sentence": "The review includes 26 trials comparing salmeterol to placebo and eight trials comparing with salbutamol. These included 62,815 participants with asthma (including 2,599 children). In six trials (2,766 patients), no serious adverse event data could be obtained. All-cause mortality was higher with regular salmeterol than placebo but the increase was not significant (Peto odds ratio (OR) 1.33 (95% CI 0.85 to 2.08)). Non-fatal serious adverse events were significantly increased when regular salmeterol was compared with placebo (OR 1.15 95% CI 1.02 to 1.29). One extra serious adverse event occurred over 28 weeks for every 188 people treated with regular salmeterol (95% CI 95 to 2606). There is insufficient evidence to assess whether the risk in children is higher or lower than in adults. We found no significant increase in fatal or non-fatal serious adverse events when regular salmeterol was compared with regular salbutamol. We combined individual patient data from the two largest studies (SNS: n=25,180 and SMART: n=26,355), as all the asthma-related deaths in adults occurred in these studies. In patients who were not taking inhaled corticosteroids, compared to regular salbutamol or placebo, there was a significant increase in risk of asthma-related death with regular salmeterol (Peto OR 6.15 95% CI 1.73 to 21.84). The confidence interval for patients who were taking inhaled corticosteroids is wide and cannot rule in or out an increase in asthma mortality in the presence of an inhaled corticosteroid (Peto OR 2.03 95% CI 0.82 to 5.00). In comparison with placebo, we have found an increased risk of serious adverse events with regular salmeterol. There is also a clear increase in risk of asthma-related mortality in patients not using inhaled corticosteroids in the two large surveillance studies. Although the increase in asthma-related mortality was smaller in patients taking inhaled corticosteroids at baseline, the confidence interval is wide, so we cannot conclude that the inhaled corticosteroids abolish the risks of regular salmeterol. The adverse effects of regular salmeterol in children remain uncertain due to the small number of children studied.",
        "gold": "There was no statistically significant difference in the number of people who died during treatment with salmeterol compared with placebo or salbutamol. Because so few people die of asthma, huge trials or observational studies are normally required to detect a difference in death rates from asthma. There were more non-fatal serious adverse events in people taking salmeterol compared to those on placebo; for every 188 people treated with salmeterol for 28 weeks, one extra non-fatal event occurred in comparison with placebo. There was no significant differences in serious adverse events in people on salmeterol compared to regular salbutamol. In order to obtain individual patient data on asthma deaths, we looked separately at mortality in two large trials on over 51,000 patients who were not taking inhaled corticosteroids, and found that there was an increase in the number of asthma-related deaths among people on salmeterol. We conclude that, for patients whose asthma is not well-controlled on moderate doses of inhaled corticosteroids, additional salmeterol can improve symptoms but this may be at the expense of an increased risk of serious adverse events and asthma related mortality.\u00a0Salmeterol should not be used as a substitute for inhaled corticosteroids, and adherence with inhaled steroids should be kept under review if separate inhalers are used. Salmeterol should not be taken by people who are not taking regular inhaled steroids due to the increased risk of asthma-related death."
    },
    {
        "index": "cochrane-simplification-test-468",
        "sentence": "Two studies enrolled preterm infants with respiratory distress. Amato (1988) allocated infants to L-thyroxine 50 \u03bcg/dose at 1 and at 24 hours or no treatment. Amato (1989) allocated infants to L-triiodothyronine 50 \u03bcg/day in two divided doses for two days or no treatment. Both studies had methodological concerns including quasi-random methods of patient allocation, no blinding of treatment or measurement and substantial post allocation losses. Neither study reported any significant benefits in neonatal morbidity or mortality from use of thyroid hormones. Meta-analysis of two studies (80 infants) found no significant difference in mortality to discharge (typical RR 1.00, 95% CI 0.47, 2.14). Amato 1988 reported no significant difference in use of mechanical ventilation (RR 0.64, 95% CI 0.38, 1.09). No significant effects were found in use of mechanical ventilation, duration of mechanical ventilation, air leak, CLD at 28 days in survivors, patent ductus arteriosus, intraventricular haemorrhage or necrotising enterocolitis. Neurodevelopment was not reported. There is no evidence from controlled clinical trials that postnatal thyroid hormone treatment reduces the severity of respiratory distress syndrome, neonatal morbidity or mortality in preterm infants with respiratory distress syndrome.",
        "gold": "This review found two small trials that compared the use of thyroid hormones to no treatment in infants with breathing problems in the first hours after birth. No benefit was found from use of these hormones on severity of breathing problems or complications that occurred as a result of these breathing problems. The effect on longer term development was not reported."
    },
    {
        "index": "cochrane-simplification-test-469",
        "sentence": "We included 38 RCTs with a total of 1828 participants. Eight RCTs had a low risk of bias in the assessment of mortality. All trials had a high risk of bias in the assessment of the remaining outcomes. Random-effects meta-analysis showed a beneficial effect of non-absorbable disaccharides versus placebo/no intervention on mortality when including all RCTs with extractable data (RR 0.59, 95% CI 0.40 to 0.87; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence) and in the eight RCTs with a low risk of bias (RR 0.63, 95% CI 0.41 to 0.97; 705 participants). The Trial Sequential Analysis with the relative risk reduction (RRR) reduced to 30% confirmed the findings when including all RCTs, but not when including only RCTs with a low risk of bias or when we reduced the RRR to 22%. Compared with placebo/no intervention, the non-absorbable disaccharides were associated with beneficial effects on hepatic encephalopathy (RR 0.58, 95% CI 0.50 to 0.69; 1415 participants; 22 RCTs; I2 = 32%; moderate quality evidence). Additional analyses showed that non-absorbable disaccharides can help to reduce serious adverse events associated with the underlying liver disease including liver failure, hepatorenal syndrome, and variceal bleeding (RR 0.47, 95% CI 0.36 to 0.60; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence). We confirmed the results in Trial Sequential Analysis. Tests for subgroup differences showed no statistical differences between RCTs evaluating prevention, overt, or minimal hepatic encephalopathy. The evaluation of secondary outcomes showed a potential beneficial effect of the non-absorbable disaccharides on quality of life, but we were not able to include the data in an overall meta-analysis (very low quality evidence). Non-absorbable disaccharides were associated with non-serious (mainly gastrointestinal) adverse events (very low quality evidence). None of the RCTs comparing lactulose versus lactitol evaluated quality of life. The review found no differences between lactulose and lactitol for the remaining outcomes (very low quality evidence). This review includes a large number of RCTs evaluating the prevention or treatment of hepatic encephalopathy. The analyses found evidence that non-absorbable disaccharides may be associated with a beneficial effect on clinically relevant outcomes compared with placebo/no intervention.",
        "gold": "We included 29 RCTs comparing non-absorbable disaccharides with inactive placebo or no intervention and nine RCTs comparing lactulose with lactitol. Seven of the included RCTs evaluated the prevention of hepatic encephalopathy and 31 evaluated the treatment of hepatic encephalopathy. Sixteen of the treatment RCTs included people with overt hepatic encephalopathy while 15 included people with minimal hepatic encephalopathy. The duration of treatment varied depending on the type of hepatic encephalopathy from five days to one year. People who received non-absorbable disaccharides were less likely to die than people given a placebo or no treatment. They were also less likely to develop serious complications of their liver disease such as liver failure, bleeding, and infections. The non-absorbable disaccharides were also effective in preventing the development of hepatic encephalopathy and increased the number of participants who recovered from hepatic encephalopathy. There was some evidence from a small number of trials that lactulose has a beneficial effect on the quality of life, but we were unable to include the data in an overall analysis. The non-absorbable disaccharides were associated with adverse events including diarrhoea, nausea, bloating, and flatulence. None of the RCTs comparing lactulose versus lactitol reported quality of life. The analyses showed no differences between the two interventions for the remaining outcomes. In the comparison of non-absorbable disaccharides versus placebo/no intervention, we found moderate quality evidence of benefit for the outcomes of death, hepatic encephalopathy, and serious complications. The evidence for the remaining outcomes was of very low quality."
    },
    {
        "index": "cochrane-simplification-test-470",
        "sentence": "In this 2019 update, 65 studies (involving 3598 participants) were eligible; 45 studies contributed data to our meta-analyses (2698 participants). Treatments included bisphosphonates, vitamin D compounds, teriparatide, denosumab, cinacalcet, parathyroidectomy, and calcitonin. Median duration of follow-up was 12 months. Forty-three studies evaluated bone density or bone-related biomarkers, with more recent studies evaluating proteinuria and hyperparathyroidism. Bisphosphonate therapy was usually commenced in the perioperative transplantation period (within 3 weeks) and regardless of BMD. Risks of bias were generally high or unclear leading to lower certainty in the results. A single study reported outcomes among 60 children and adolescents. Studies were not designed to measure treatment effects on fracture, death or cardiovascular outcomes, or graft loss. Compared to placebo, bisphosphonate therapy administered over 12 months in transplant recipients may prevent fracture (RR 0.62, 95% CI 0.38 to 1.01; low certainty evidence) although the 95% CI included the possibility that bisphosphonate therapy might make little or no difference. Fracture events were principally vertebral fractures identified during routine radiographic surveillance. It was uncertain whether any other drug class decreased fracture (low or very low certainty evidence). It was uncertain whether interventions for bone disease in kidney transplantation reduce all-cause or cardiovascular death, myocardial infarction or stroke, or graft loss in very low certainty evidence. Bisphosphonate therapy may decrease acute graft rejection (RR 0.70, 95% CI 0.55 to 0.89; low certainty evidence), while it is uncertain whether any other treatment impacts graft rejection (very low certainty evidence). Bisphosphonate therapy may reduce bone pain (RR 0.20, 95% CI 0.04 to 0.93; very low certainty evidence), while it was very uncertain whether bisphosphonates prevent spinal deformity or avascular bone necrosis (very low certainty evidence). Bisphosphonates may increase to risk of hypocalcaemia (RR 5.59, 95% CI 1.00 to 31.06; low certainty evidence). It was uncertain whether vitamin D compounds had any effect on skeletal, cardiovascular, death, or transplant function outcomes (very low certainty or absence of evidence). Evidence for the benefits and harms of all other treatments was of very low certainty. Evidence for children and young adolescents was sparse. Bisphosphonate therapy may reduce fracture and bone pain after kidney transplantation, however low certainty in the evidence indicates it is possible that treatment may make little or no difference. It is uncertain whether bisphosphonate therapy or other bone treatments prevent other skeletal complications after kidney transplantation, including spinal deformity or avascular bone necrosis. The effects of bone treatment for children and adolescents after kidney transplantation are very uncertain.",
        "gold": "In 2019, there are 65 research studies (involving 3598 people) that looked at whether medicines can prevent bone fractures after kidney transplant. The most common medicine in the studies was a bisphosphonate which slows bone breakdown. Bisphosphonates were given at around the time of kidney transplantation (generally just before or within a few weeks) and continued for about one year on average. Other treatment options in the studies were vitamin D, calcitonin, denosumab, teriparatide, or cinacalcet. Bisphosphonate treatment given after a transplant possibly prevents fractures and bone pain, however the range where the actual effect of treatment might be (the \"margin of error\") indicates that treatment might make little or no difference. Bisphosphonates possibly lower the chances of a rejection of the transplant kidney but because of problems with the research studies, we can't be very certain that this is true. Bisphosphonates caused low blood calcium levels for some people. There was low or very low confidence in the information about all the other possible treatments for bone fractures after a kidney transplant, as the studies were often too small. There was only one study for medicines in children so we don't know whether these drugs are useful and safe for younger people. It is still unclear whether bisphosphonate therapy makes any difference to bone fractures or are safe for both adults and children with a kidney transplant."
    },
    {
        "index": "cochrane-simplification-test-471",
        "sentence": "Four trials involving 317 people met the inclusion criteria. Three trials studied oral magnesium, with doses ranging from 12.5 mmol/day to 20 mmol/day. One trial studied parenteral magnesium (16.24 mEq q6h for 24 hours). Each trial demonstrated a high risk of bias in at least one domain. There was significant clinical and methodological variation between trials. We found no study that measured all of the identified primary outcomes and met the objectives of this review. Only one trial measured clinical symptoms of seizure, delirium tremens or components of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score. A single outcome (handgrip strength) in three trials (113 people), was amenable to meta-analysis. There was no significant increase in handgrip strength in the magnesium group (SMD 0.04; 95% CI -0.22 to 0.30). No clinically important changes in adverse events were reported. There is insufficient evidence to determine whether magnesium is beneficial or harmful for the treatment or prevention of alcohol withdrawal syndrome.",
        "gold": "Alcohol withdrawal syndrome (AWS) is a set of symptoms experienced when one reduces or stops alcohol consumption after prolonged periods of alcohol intake. Some studies show that AWS coincides with low levels of magnesium in the blood. Since magnesium may play a role in dampening the excitability of the central nervous system, some researchers believe that low levels of magnesium may make the central nervous system 'hyper-excitable' and may cause AWS symptoms, which include sleeplessness, tremors, anxiety, headache, excessive sweating and reduced appetite. Many AWS treatment protocols therefore recommend magnesium supplementation. The goal of our review was to determine whether magnesium supplementation prevents or treats AWS in adults. Our review of four trials covering 317 participants determined that there is not enough evidence about the benefits or harms of using magnesium supplements to prevent or treat AWS in adults."
    },
    {
        "index": "cochrane-simplification-test-472",
        "sentence": "We included 15 trials involving 3057 participants. Of the 15 included trials, 10 appeared in our 2012 review, and five (631 participants) are legacy trials from merging two reviews. No new studies were included from searches for this update. Overall, risk of bias was low. Without antibiotics, 46% of participants with rhinosinusitis, whether or not confirmed by radiography, were cured after 1 week and 64% after 14 days. Antibiotics can shorten time to cure, but only 5 to 11 more people per 100 will be cured faster if they receive antibiotics instead of placebo or no treatment: clinical diagnosis (odds ratio (OR) 1.25, 95% confidence interval (CI) 1.02 to 1.54; number needed to treat for an additional beneficial outcome (NNTB) 19, 95% CI 10 to 205; I\u00b2 = 0%; 8 trials; high-quality evidence) and diagnosis confirmed by radiography (OR 1.57, 95% CI 1.03 to 2.39; NNTB 10, 95% CI 5 to 136; I\u00b2 = 0%; 3 trials; moderate-quality evidence). Cure rates with antibiotics were higher when a fluid level or total opacification in any sinus was found on computed tomography (OR 4.89, 95% CI 1.75 to 13.72; NNTB 4, 95% CI 2 to 15; 1 trial; moderate-quality evidence). Purulent secretion resolved faster with antibiotics (OR 1.58, 95% CI 1.13 to 2.22; NNTB 10, 95% CI 6 to 35; I\u00b2 = 0%; 3 trials; high-quality evidence). However, 13 more people experienced side effects with antibiotics compared to placebo or no treatment (OR 2.21, 95% CI 1.74 to 2.82; number needed to treat for an additional harmful outcome (NNTH) 8, 95% CI 6 to 12; I\u00b2 = 16%; 10 trials; high-quality evidence). Five fewer people per 100 will experience clinical failure if they receive antibiotics instead of placebo or no treatment (Peto OR 0.48, 95% CI 0.36 to 0.63; NNTH 19, 95% CI 15 to 27; I\u00b2 = 21%; 12 trials; high-quality evidence). A disease-related complication (brain abscess) occurred in one participant (of 3057) one week after receiving open antibiotic therapy (clinical failure, control group). The potential benefit of antibiotics to treat acute rhinosinusitis diagnosed either clinically (low risk of bias, high-quality evidence) or confirmed by imaging (low to unclear risk of bias, moderate-quality evidence) is marginal and needs to be seen in the context of the risk of adverse effects. Considering antibiotic resistance, and the very low incidence of serious complications, we conclude there is no place for antibiotics for people with uncomplicated acute rhinosinusitis. We could not draw conclusions about children, people with suppressed immune systems, and those with severe sinusitis, because these populations were not included in the available trials.",
        "gold": "We included 15 studies in which adults with short-duration sinus infection, whether or not confirmed by imaging, randomly received antibiotics, or a dummy drug or no treatment, in ambulatory care settings. The studies included a total of 3057 adults whose average age was 36 years; about 60% were female. Participants were followed until they were cured. Trial duration ranged from 8 to 28 days. Seven studies received financial support from government or academic institutions; six received grants from the pharmaceutical industry; and five did not state sources of support. Without antibiotics, almost half of all participants were cured after one week, and two out of three were cured after 14 days. Five (diagnosis based on symptoms described to a doctor) to 11 (diagnosis confirmed by x-ray) more people per 100 were cured faster with antibiotics. A computed tomography (CT) scan could better predict who would benefit from antibiotics, but routine use would cause health problems related to radiation exposure. Ten more people per 100 were relieved faster of thick, yellow discharge from the nose with antibiotics compared to a dummy drug or no treatment. Thirteen more people per 100 experienced side effects (mostly concerning stomach or intestines) with antibiotics compared to a dummy drug or no treatment. Compared with people who initially started antibiotics, five more people per 100 in the dummy drug or no treatment group had to start antibiotics because their condition worsened. Serious complications (e.g. brain abscess) were rare. We found that antibiotics are not a first-choice treatment for adults with short-duration sinus infection. We found no evidence relating to adults with severe sinusitis or with reduced immunity, or to children. We found high-quality evidence when the diagnosis was based on symptoms described to a doctor. We downgraded evidence quality to moderate when diagnosis was confirmed by x-ray or CT scan because the number of participants was small, which makes the estimates less reliable."
    },
    {
        "index": "cochrane-simplification-test-473",
        "sentence": "Eight RCTs (enrolling 2515 patients) met the inclusion criteria. Three RCTs (all performed in Asian countries) compared D3 with D2 lymphadenectomy: data suggested no significant difference in OS between these two types of lymph node dissection (HR 0.99, 95% CI 0.81 to 1.21), with no significant difference in postoperative mortality (RR 1.67, 95% CI 0.41 to 6.73). Data for DFS were available only from one trial and for no trial were DSS data available. Five RCTs (n = 3 European; n = 2 Asian) compared D2 to D1 lymphadenectomy: OS (n = 5; HR 0.91, 95% CI 0.71 to 1.17) and DFS (n=3; HR 0.95, 95% CI 0.84 to 1.07) findings suggested no significant difference between these two types of lymph node dissection. In contrast, D2 lymphadenectomy was associated with a significantly better DSS compared to D1 lymphadenectomy (HR 0.81, 95% CI 0.71 to 0.92), the quality of the body of evidence being moderate; however, D2 lymphadenectomy was also associated with a higher postoperative mortality rate (RR 2.02, 95% CI 1.34 to 3.04). D2 lymphadenectomy can improve DSS in patients with resectable carcinoma of the stomach, although the increased incidence of postoperative mortality reduces its therapeutic benefit.",
        "gold": "We collected data from eight randomized controlled trials addressing this issue and enrolling a total of 2515 patients. We found that D2 lymphadenectomy can reduce the number of deaths due to disease progression as compared to D1 lymphadenectomy. However, D2 lymphadenectomy was also associated with a higher rate of postoperative mortality. In addition, available evidence does not support the superiority of D3 versus D2 lymphadenectomy. In conclusion, our findings support the use of D2 lymphadenectomy in patients with resectable carcinoma of the stomach, although the increased incidence of postoperative mortality reduces its therapeutic effect. The quality of the evidence was moderate due to an intermediate level of result heterogeneity across the included trials."
    },
    {
        "index": "cochrane-simplification-test-474",
        "sentence": "Thirteen studies, 1158 participants, met the criteria for inclusion in this review. Comparing naltrexone versus placebo or no pharmacological treatments, no statistically significant difference were noted for all the primary outcomes considered. The only outcome statistically significant in favour of naltrexone is re incarceration, RR 0.47 (95%CI 0.26-0.84), but results come only from two studies. Considering only studies were patients were forced to adherence a statistical significant difference in favour of naltrexone was found for retention and abstinence, RR 2.93 (95%CI 1.66-5.18). Comparing naltrexone versus psychotherapy, in the two considered outcomes, no statistically significant difference was found in the single study considered. Naltrexone was not superior to benzodiazepines and to buprenorphine for retention and abstinence and side effects. Results come from single studies. The findings of this review suggest that oral naltrexone did not perform better than treatment with placebo or no pharmacological agent with respect to the number of participants re-incarcerated during the study period. If oral naltrexone is compared with other pharmacological treatments such as benzodiazepine and buprenorphine, no statistically significant difference was found. The percentage of people retained in treatment in the included studies is however low (28%). The conclusion of this review is that the studies conducted have not allowed an adequate evaluation of oral naltrexone treatment in the field of opioid dependence. Consequently, maintenance therapy with naltrexone cannot yet be considered a treatment which has been scientifically proved to be superior to other kinds of treatment.",
        "gold": "In this review of the medical literature oral naltrexone, with or without psychotherapy, was no better than placebo or no pharmacological treatments with regard to retention in treatment, use of the primary substance of abuse or side effects. The only outcome that was clearly in favour of naltrexone was a reduction of re incarcerations by about a half but these results were from only two studies. In single studies naltrexone was not superior to benzodiazepines or buprenorphine for retention, abstinence or side effects. The review authors identified a total of 13 randomised controlled studies that involved 1158 opioid addicts treated as outpatients following detoxification. Less than a third of participants were retained in treatment over the duration of the included studies. The mean duration was six months (range one to 10 months). None of included studies considered deaths from fatal overdoses in people treated with naltrexone."
    },
    {
        "index": "cochrane-simplification-test-475",
        "sentence": "No trials on modification of food met the inclusion criteria. We included two studies that examined modification to fluids. Both were part of the same large multicentre trial and included people with dementia and people with or without dementia and Parkinson's disease. Participation in the second trial was determined by results from the first trial. With unpublished data supplied by study authors, we examined data from participants with dementia only. The first study, a cross-over trial, investigated the immediate effects on aspiration of two viscosities of liquids (nectar thick and honey thick) compared to regular liquids in 351 participants with dementia using videofluoroscopy. Regular liquids with a chin down head posture, as well as regular liquids without any intervention were also compared. The sequence of interventions during videofluoroscopy may have influenced response to intervention. The second study, a parallel designed RCT, compared the effect of nectar and honey thick liquids with a chin down head posture over a three-month period in a subgroup of 260 participants with dementia. Outcomes were pneumonia and adverse intervention effects. Honey thick liquids, which are more consistent with descriptors for 'spoon thick' or 'extremely thick' liquids, showed a more positive impact on immediate elimination of aspiration during videofluoroscopy, but this consistency showed more adverse effects in the second follow-up study. During the second three-month follow-up trial, there were a greater number of incidents of pneumonia in participants receiving honey thick liquids than those receiving nectar thick liquids or taking regular liquids with a chin down posture. There were no deaths classified as 'definitely related' to the type of fluids prescribed. Neither trial addressed quality of life. Risk of bias for both studies is high. The overall quality of evidence for outcomes in this review is low. We are uncertain about the immediate and long-term effects of modifying the consistency of fluid for swallowing difficulties in dementia as too few studies have been completed. There may be differences in outcomes depending on the grade of thickness of fluids and the sequence of interventions trialled in videofluoroscopy for people with dementia. Clinicians should be aware that while thickening fluids may have an immediate positive effect on swallowing, the long-term impact of thickened fluids on the health of the person with dementia should be considered. Further high-quality clinical trials are required.",
        "gold": "We found two studies, which were both part of the same multicentre trial and included people with dementia and people with or without dementia and Parkinson's disease. We included data on people with dementia only. The first of the two studies looked at the immediate effects of two viscosities of liquids compared to regular thin liquids on aspiration (entry of food or fluid into the lungs) in 351 people with dementia. This study also compared drinking regular thin liquids using a chin down head posture as well as drinking regular thin liquids without any changes to head position; the main outcome was fluid entering the lungs. Using a subgroup of 260 people with dementia from the first study, the second study compared the effect of the same liquid viscosities with a chin down head posture. The effectiveness of these interventions on the incidence of pneumonia and adverse effects of these interventions was examined over a three-month period. Honey thick viscosity liquids, which clinically are similar to descriptions of 'very thick liquids', had a more positive immediate impact on preventing fluid entering the lungs when examined during videofluoroscopy (specialised swallow x-ray) examination. However, during the three-month follow-up period there were a greater number of incidents of pneumonia in the group of people with dementia receiving these honey thick liquids, than those receiving nectar thick liquids and those receiving regular thin liquids with a chin down posture. There were no deaths classified as 'definitely related' to the type of liquids that the person with dementia was receiving. There were a number of methodological flaws in both studies in this review and these were acknowledged by the authors. While thickening fluids may have an immediate positive effect on swallow function, clinicians should consider the effects of this intervention on the person with dementia in the longer-term. People with dementia on thickened fluids require long-term follow-up. The overall risk of bias of included studies is high. The quality of evidence is low. Further well-designed research is needed."
    },
    {
        "index": "cochrane-simplification-test-476",
        "sentence": "Six randomised controlled trials with a total of 788 women were included. The largest of these trials included 396 women eligible for this review. No evidence of a statistically significant difference was found between natural cycle and standard IVF in live birth rates (OR 0.68, 95% CI 0.46 to 1.01, two studies, 425 women, I2= 0%, moderate quality evidence). The evidence suggests that for a woman with a 53% chance of live birth using standard IVF, the chance using natural cycle IVF would range from 34% to 53%. There was no evidence of a statistically significant difference between natural cycle and standard IVF in rates of OHSS (OR 0.19, 95% CI 0.01 to 4.06, one study, 60 women, very low quality evidence), clinical pregnancy (OR 0.52 95% CI 0.17 to 1.61, 4 studies, 351 women, I2=63%, low quality evidence), ongoing pregnancy (OR 0.72, 95% CI 0.50 to 1.05, three studies, 485 women, I2=0%, moderate quality evidence), multiple pregnancy (OR 0.76, 95% CI 0.25 to 2.31, 2 studies, 527 women, I2=0%, very low quality evidence), gestational abnormalities (OR 0.44 95% CI 0.03 to 5.93, 1 study, 18 women, very low quality evidence) or cycle cancellations (OR 8.98, 95% CI 0.20 to 393.66, 2 studies, 159 women, I2=83%, very low quality evidence). One trial reported that the oocyte retrieval rate was significantly lower in the natural cycle group (MD -4.40, 95% CI -7.87 to -0.93, 60 women, very low quality evidence). There were insufficient data to draw any conclusions about rates of treatment cancellation. Findings on treatment costs were inconsistent and more data are awaited. The evidence was limited by imprecision. Findings for pregnancy rate and for cycle cancellation were sensitive to the choice of statistical model: for these outcomes, use of a fixed effect model suggested a benefit for the standard IVF group. Moreover the largest trial has not yet completed follow up, though data have been reported for over 95% of women. Further evidence from well conducted large trials is awaited on natural cycle IVF treatment. Future trials should compare natural cycle IVF with standard IVF. Outcomes should include cumulative live birth and pregnancy rates, the number of treatment cycles necessary to reach live birth, treatment costs and adverse effects.",
        "gold": "Six trials were included, with a total of 788 women undergoing an IVF treatment. The evidence is current to 31st July 2013. The largest trial in the review (with 396 women) has not yet reported full results. The evidence suggested that for a woman with a 53% chance of live birth using standard IVF, the chance using natural cycle IVF ranges from 34% to 53%. No significant difference was found in rates of clinical pregnancy, ongoing pregnancy, multiple pregnancy, incidence of ovarian hyperstimulation syndrome, gestational abnormalities or cancellations of treatment. However findings were imprecise for all outcomes and further evidence from larger studies is awaited. There was evidence from single studies that a lower number of oocytes was retrieved in the natural cycle group. Findings on cost-effectiveness were inconsistent. Quality ratings for the evidence ranged from very low to moderate, the main limitation being imprecision due to insufficient data. When the review authors checked the effect of using an alternative method of analysis the findings suggested higher rates of clinical pregnancy with standard IVF than with natural cycle IVF."
    },
    {
        "index": "cochrane-simplification-test-477",
        "sentence": "We included a total of 984 participants from 12 studies (23 references) in this analysis. We included only those involved in Tai Chi and the control group (i.e. 811 participants) in the final analysis. Study sample size ranged from 10 to 206, and mean age ranged from 61 to 74 years. Programmes lasted for six weeks to one year. All included studies were RCTs; three studies used allocation concealment, six reported blinded outcome assessors and three studies adopted an intention-to-treat approach to statistical analysis. No adverse events were reported. Quality of evidence of the outcomes ranged from very low to moderate. Analysis was split into three comparisons: (1) Tai Chi versus usual care; (2) Tai Chi and breathing exercise versus breathing exercise alone; and (3) Tai Chi and exercise versus exercise alone. Comparison of Tai Chi versus usual care revealed that Tai Chi demonstrated a longer six-minute walk distance (mean difference (MD) 29.64 metres, 95% confidence interval (CI) 10.52 to 48.77 metres; participants = 318; I2 = 59%) and better pulmonary function (i.e. forced expiratory volume in one second, MD 0.11 L, 95% CI 0.02 to 0.20 L; participants = 258; I2 = 0%) in post-programme data. However, the effects of Tai Chi in reducing dyspnoea level and improving quality of life remain inconclusive. Data are currently insufficient for evaluating the impact of Tai Chi on maximal exercise capacity, balance and muscle strength in people with COPD. Comparison of Tai Chi and other interventions (i.e. breathing exercise or exercise) versus other interventions shows no superiority and no additional effects on symptom improvement nor on physical and psychosocial outcomes with Tai Chi. No adverse events were reported, implying that Tai Chi is safe to practise in people with COPD. Evidence of very low to moderate quality suggests better functional capacity and pulmonary function in post-programme data for Tai Chi versus usual care. When Tai Chi in addition to other interventions was compared with other interventions alone, Tai Chi did not show superiority and showed no additional effects on symptoms nor on physical and psychosocial function improvement in people with COPD. With the diverse style and number of forms being adopted in different studies, the most beneficial protocol of Tai Chi style and number of forms could not be commented upon. Hence, future studies are warranted to address these topics.",
        "gold": "We included a total of 811 participants from 12 studies in the final analysis of this review. The number of participants in each study ranged from 10 to 206, and mean age ranged from 61 to 74 years. The programme lasted for six weeks to one year. Included studies adopted different styles and numerous forms of Tai Chi. The most commonly reported form is the simplified 24-form Yang-style Tai Chi. No unwanted events or side effects were reported throughout the study period. Quality of evidence of all outcomes of interest ranged from very low to moderate. After training was completed, levels of shortness of breath in Tai Chi and control (i.e. usual care) groups were similar. Participants in the Tai Chi group walked farther, by 29.64 metres in six minutes, and had better pulmonary function, than those who received usual care. However, changes in quality of life were not apparent. When the effect of Tai Chi used in addition to another intervention (i.e. breathing exercise or exercise) was examined, we did not find that Tai Chi offered additional benefit in terms of shortness of breath or functional and psychosocial well-being. Currently, only one study has investigated the beneficial effects of Tai Chi on muscle strength and balance; investigators provided insufficient information to allow comment on the data in this review. Future studies addressing these topics are warranted."
    },
    {
        "index": "cochrane-simplification-test-478",
        "sentence": "We included 72 trials that involved 2470 participants. This review includes 35 new studies in addition to the studies included in the previous version of this review. Study sample sizes were generally small and interventions varied in terms of both the goals of treatment and the virtual reality devices used. The risk of bias present in many studies was unclear due to poor reporting. Thus, while there are a large number of randomised controlled trials, the evidence remains mostly low quality when rated using the GRADE system. Control groups usually received no intervention or therapy based on a standard-care approach. Primary outcome: results were not statistically significant for upper limb function (standardised mean difference (SMD) 0.07, 95% confidence intervals (CI) -0.05 to 0.20, 22 studies, 1038 participants, low-quality evidence) when comparing virtual reality to conventional therapy. However, when virtual reality was used in addition to usual care (providing a higher dose of therapy for those in the intervention group) there was a statistically significant difference between groups (SMD 0.49, 0.21 to 0.77, 10 studies, 210 participants, low-quality evidence). Secondary outcomes: when compared to conventional therapy approaches there were no statistically significant effects for gait speed or balance. Results were statistically significant for the activities of daily living (ADL) outcome (SMD 0.25, 95% CI 0.06 to 0.43, 10 studies, 466 participants, moderate-quality evidence); however, we were unable to pool results for cognitive function, participation restriction, or quality of life. Twenty-three studies reported that they monitored for adverse events; across these studies there were few adverse events and those reported were relatively mild. We found evidence that the use of virtual reality and interactive video gaming was not more beneficial than conventional therapy approaches in improving upper limb function. Virtual reality may be beneficial in improving upper limb function and activities of daily living function when used as an adjunct to usual care (to increase overall therapy time). There was insufficient evidence to reach conclusions about the effect of virtual reality and interactive video gaming on gait speed, balance, participation, or quality of life. This review found that time since onset of stroke, severity of impairment, and the type of device (commercial or customised) were not strong influencers of outcome. There was a trend suggesting that higher dose (more than 15 hours of total intervention) was preferable as were customised virtual reality programs; however, these findings were not statistically significant.",
        "gold": "We identified 72 studies involving 2470 people after stroke. A wide range of virtual reality programs were used, with most aimed to improve either arm function or walking ability. The evidence is current to April 2017. Twenty-two trials tested whether the use of virtual reality compared with conventional therapy resulted in an improved ability to use one's arm and found that the use of virtual reality did not result in better function (low-quality evidence). When virtual reality was used in addition to usual care or rehabilitation to increase the amount of time the person spent in therapy there were improvements in the functioning of the arm (low-quality evidence). Six trials tested whether the use of virtual reality compared with conventional therapy resulted in improved walking speed. There was no evidence that virtual reality was more effective in this case (low-quality evidence). Ten trials found that there was some evidence that virtual reality resulted in a slightly better ability to manage everyday activities such as showering and dressing (moderate-quality evidence). However, these positive effects were found soon after the end of the treatment and it is not clear whether the effects are long lasting. Results should be interpreted with caution as, while there are a large number of studies, the studies are generally small and not of high quality. A small number of people using virtual reality reported pain, headaches, or dizziness. No serious adverse events were reported. The quality of the evidence was generally of low or moderate quality. The quality of the evidence for each outcome was limited due to small numbers of study participants, inconsistent results across studies, and poor reporting of study details."
    },
    {
        "index": "cochrane-simplification-test-479",
        "sentence": "We identified five RCTs (1330 participants) that met the inclusion criteria. None of the included trials examined regimens of less than six months duration. Fluoroquinolones added to standard regimens A single trial (174 participants) added levofloxacin to the standard first-line regimen. Relapse and treatment failure were not reported. For death, sputum conversion, and adverse events we are uncertain if there is an effect (one trial, 174 participants, very low quality evidence for all three outcomes). Fluoroquinolones substituted for ethambutol in standard regimens Three trials (723 participants) substituted ethambutol with moxifloxacin, gatifloxacin, and ofloxacin into the standard first-line regimen. For relapse, we are uncertain if there is an effect (one trial, 170 participants, very low quality evidence). No trials reported on treatment failure. For death, sputum culture conversion at eight weeks, or serious adverse events we do not know if there was an effect (three trials, 723 participants, very low quality evidence for all three outcomes). Fluoroquinolones substituted for isoniazid in standard regimens A single trial (433 participants) substituted moxifloxacin for isoniazid. Treatment failure and relapse were not reported. For death, sputum culture conversion, or serious adverse events the substitution may have little or no difference (one trial, 433 participants, low quality evidence for all three outcomes). Fluoroquinolines in four month regimens Six trials are currently in progress testing shorter regimens with fluoroquinolones. Ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin have been tested in RCTs of standard first-line regimens based on rifampicin and pyrazinamide for treating drug-sensitive TB. There is insufficient evidence to be clear whether addition or substitution of fluoroquinolones for ethambutol or isoniazid in the first-line regimen reduces death or relapse, or increases culture conversion at eight weeks. Much larger trials with fluoroquinolones in short course regimens of four months are currently in progress.",
        "gold": "We examined the research published up to 6 March 2013 and we identified five randomised controlled trials (1330 people) that met the inclusion criteria. The trials were performed in low- and middle-income countries located in geographically diverse areas but there was a lack of studies conducted in Asia. We found no studies that examined the effect of including fluoroquinolones in a standard six month TB treatment regimen on treatment failure. We do not know whether adding fluoroquinolones or substituting fluoroquinolones for ethambutol in a standard six month TB treatment regimen reduces treatment failure, relapse, death, or adverse events. Substituting fluoroquinolones for isoniazid in a standard six month TB treatment regimen may have little or no difference upon death and adverse events. Currently, there are nine randomised controlled trials ongoing. HIV-positive participants were relatively well-represented in the included trials but none of the included trials stratified outcomes by HIV status. Also, the primary outcomes of all the included trials were reached before initiation of antiretroviral treatment. Evidence is generally lacking on the safety and efficacy of fluoroquinolone additions or substitutions in children (< 18 years) and in pregnant and lactating women."
    }
]