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We included three studies involving 275 women (data reported for 271) with PPROM at up to 34 weeks' gestation. All three studies were conducted in the United States. Each study investigated different methods of fetal assessment. One study compared weekly endovaginal ultrasound scans with no assessment (n = 93), one compared amniocentesis with no assessment (n = 47), and one compared daily nonstress testing with daily modified biophysical profiling (n = 135). We were unable to perform a meta-analysis, but were able to report data from individual studies. There was no convincing evidence of increased risk of neonatal death in the group receiving endovaginal ultrasound scans compared with the group receiving no assessment (risk ratio (RR) 7.30, 95% confidence interval (CI) 0.39 to 137.54; one study, 92 women), or in the group receiving amniocentesis compared with the group receiving no amniocentesis (RR 1.00, 95% CI 0.07 to 15.00; one study, 44 women). For both these interventions, we inferred that there were no fetal deaths in the intervention or control groups. The study comparing daily nonstress testing with daily modified biophysical profiling did not report fetal or neonatal death. Primary outcomes of maternal death and serious maternal morbidity were not reported in any study. Overall, there were few statistically significant differences in outcomes between the comparisons. The overall quality of evidence is poor, because participant blinding was not possible for any study. There is insufficient evidence on the benefits and harms of fetal assessment methods for improving neonatal and maternal outcomes in women with PPROM to draw firm conclusions. The overall quality of evidence that does exist is poor. Further high-quality randomised controlled trials are required to guide clinical practice. | This review was carried out to evaluate whether these methods lead to improved health outcomes for the mother and her baby. The review included three randomised controlled studies that involved a total of 275 women (data reported for 271) with PPROM at up to 34 weeks' gestation. All three studies were from the USA. They each investigated different methods of fetal assessment, so no meta-analysis could be conducted. Instead, the review reported the results of each individual study. One study compared weekly endovaginal ultrasound scans where the probe is placed inside the vagina versus no assessment, one compared an amniotic fluid test to measure levels of fetal lung surfactant with no assessment, and one compared a daily 'nonstress test' (recording the fetal heartbeat) with daily modified biophysical profiling (recording the fetal heartbeat as well as estimating the volume of amniotic fluid surrounding the baby). In each study, there were few statistically significant differences between groups in outcomes for the mother, fetus or neonate. The overall quality of the evidence was poor, because participants knew which group they were in. More studies are needed to assess the benefits and harms of fetal assessment methods for improving neonatal and maternal outcomes in women with PPROM before firm conclusions can be drawn. |
Fifty six trials met the inclusion criteria, involving 3257 children of whom 2412 used an alarm. The quality of many trials was poor, and evidence for many comparisons was inadequate. Most alarms used audio methods. Compared to no treatment, about two thirds of children became dry during alarm use (RR for failure 0.38, 95% CI 0.33 to 0.45). Nearly half who persisted with alarm use remained dry after treatment finished, compared to almost none after no treatment (RR of failure or relapse 45 of 81 (55%) versus 80 of 81 (99%), RR 0.56, 95% CI 0.46 to 0.68). There was insufficient evidence to draw conclusions about different types of alarm, or about how alarms compare to other behavioural interventions. Relapse rates were lower when overlearning was added to alarm treatment (RR 1.92, 95% CI 1.27 to 2.92) or if dry bed training was used as well (RR 2.0, 95% CI 1.25 to 3.20). Penalties for wet beds appeared to be counter-productive. Alarms using electric shocks were unacceptable to children or their parents. Although desmopressin may have a more immediate effect, alarms appeared to be as effective by the end of a course of treatment (RR 0.85, 95% CI 0.53 to 1.37) but their relative effectiveness after stopping treatment was unclear from two small trials which compared them directly. Evidence about the benefit of supplementing alarm treatment with desmopressin was conflicting. Alarms were not significantly better than tricyclics during treatment (RR 0.59, 95% CI 0.32 to 1.09) but the relapse rate was less afterwards (7 of 12 (58%) versus 12 of 12 (100%), RR 0.58, 95% CI 0.36 to 0.94). However, other Cochrane reviews of desmopressin and tricyclics suggest that drug treatment alone, while effective for some children during treatment, is unlikely to be followed by sustained cure as almost all the children relapse. Alarm interventions are an effective treatment for nocturnal bedwetting in children. Alarms appear more effective than desmopressin or tricyclics because around half the children remain dry after alarm treatment stops. Overlearning (giving extra fluids at bedtime after successfully becoming dry using an alarm), dry bed training and avoiding penalties may further reduce the relapse rate. Better quality research comparing alarms with other treatments is needed, including follow-up to determine relapse rates. | The review of trials found 56 studies involving 3257 children. Alarm interventions reduce night-time bed wetting in about two thirds of children during treatment, and about half the children remained dry after stopping using the alarm. Alarms take longer to reduce bedwetting than desmopressin, but their effects continue after treatment in half the children who use alarms. So alarms are better in the long term than treatment with desmopressin or tricyclic drugs. Overlearning (giving children extra fluids at bedtime after successfully becoming dry using an alarm) and dry bed training (getting children to go to the toilet repeatedly and changing their own sheets when they wet) may reduce the relapse rate. There are no serious side-effects, which can occur with drug treatment. However, children need more supervision and time from other family members at first. There was not enough evidence with which to compare alarms with other non-drug treatments. Because some of the studies were of poor quality, better research comparing alarms with other treatments is needed, including follow-up to measure relapse rates. |
We included in this review 24 studies with a total of 1250 participants. The trials included various numbers and types of participants. Investigators used a range of methods to warm fluids to temperatures between 37°C and 41°C. We found that evidence was of moderate quality because descriptions of trial design were often unclear, resulting in high or unclear risk of bias due to inappropriate or unclear randomization and blinding procedures. These factors may have influenced results in some way. Our protocol specified the risk of hypothermia as the primary outcome; as no trials reported this, we decided to include data related to mean core temperature. The only secondary outcome reported in the trials that provided useable data was shivering. Evidence was unclear regarding the effects of fluid warming on bleeding. No data were reported on our other specified outcomes of cardiovascular complications, infection, pressure ulcers, bleeding, mortality, length of stay, unplanned intensive care admission and adverse events. Researchers found that warmed intravenous fluids kept the core temperature of study participants about half a degree warmer than that of participants given room temperature intravenous fluids at 30, 60, 90 and 120 minutes, and at the end of surgery. Warmed intravenous fluids also further reduced the risk of shivering compared with room temperature intravenous fluids Investigators reported no statistically significant differences in core body temperature or shivering between individuals given warmed and room temperature irrigation fluids. Warm intravenous fluids appear to keep patients warmer during surgery than room temperature fluids. It is unclear whether the actual differences in temperature are clinically meaningful, or if other benefits or harms are associated with the use of warmed fluids. It is also unclear if using fluid warming in addition to other warming methods confers any benefit, as a ceiling effect is likely when multiple methods of warming are used. | We searched medical databases up until February 2014 to find studies comparing warmed fluids with unwarmed fluids and other methods of warming the patient. We found 24 relevant trials with 1250 adult patients undergoing all types of surgery. We did not include studies for which it was intended that the patient would become cold (such as to facilitate heart bypass surgery). We had intended to collect data on which patients became hypothermic (when their body temperature dropped to below 36 degrees Celsius), but no trials reported this, so we collected data on patient temperatures at various time points throughout surgery. We found evidence of moderate quality showing that if patients had the fluids they were given into their veins warmed up, they were about half a degree Celsius warmer and shivered less than those who received unwarmed fluids; however, we were unable to show a significant difference in patients who received warmed fluids to wash out parts of their bodies. We have demonstrated that warming fluids does keep adult patients warmer; however it is unclear whether this alone can make a difference in the severe complications that becoming cold may cause. |
Two Chinese RCTs involving 158 women were included in this review. Although both these trials described adequate methodology they were of limited quality. Neither trial compared CHM with placebo treatment. There was no evidence of a significant difference in rates of symptomatic relief between CHM and gestrinone administered subsequent to laparoscopic surgery (RR 1.04, 95% CI 0.91 to 1.18). There was no significant difference between the CHM and gestrinone groups with regard to the total pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to 1.59, one RCT). CHM administered orally and then in conjunction with a herbal enema resulted in a greater proportion of women obtaining symptomatic relief than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively). Oral plus enema administration of CHM resulted in a greater reduction in average dysmenorrhoea pain scores than did danazol (mean difference (MD) -2.90, 95% CI -4.55 to -1.25). For lumbosacral pain, rectal discomfort, or vaginal nodules tenderness, there was no significant difference between CHM and danazol. Overall, 100% of women in both studies showed some improvement in their symptoms. Women taking CHM had fewer side effects than those taking either gestrinone or danazol. Post-surgical administration of CHM may have comparable benefits to gestrinone. Oral CHM may have a better overall treatment effect than danazol and it may be more effective in relieving dysmenorrhoea when used in conjunction with a CHM enema. CHM appears to have fewer side effects than either gestrinone or danazol. However, more rigorous research is required to accurately assess the potential role of CHM in treating endometriosis. | The two small studies in this review suggest that Chinese herbal medicine (CHM) may be as effective as gestrinone and may be more effective than danazol in relieving endometriosis-related pain, with fewer side effects than experienced with conventional treatment. However, the two trials included in this review were small and of limited quality so these findings must be interpreted cautiously. Better quality randomised controlled trials are needed to investigate a possible role for CHM in the treatment of endometriosis. |
We included 54 studies in the review (50 in the meta-analyses), containing 5660 patients, of whom 586 had proven or probable invasive aspergillosis. When using an optical density index (ODI) of 0.5 as a cut-off value, the sensitivity of the test was 78% (70% to 85%) and the specificity was 85% (78% to 91%). At a cut-off value of 1.0 ODI, the sensitivity was 71% (63% to 78%) and the specificity was 90% (86% to 93%). At a cut-off value of 1.5 ODI, the sensitivity was 63% (49% to 78%) and the specificity was 93% (89% to 97%). None of the potential sources of heterogeneity had a statistically significant effect on either sensitivity or specificity. If we used the test at a cut-off value of 0.5 ODI in a population of 100 patients with a disease prevalence of 11% (overall median prevalence), two patients who have invasive aspergillosis would be missed (sensitivity 78%, 22% false negatives), and 13 patients would be treated unnecessarily or referred unnecessarily for further testing (specificity 85%, 15% false negatives). If we used the test at a cut-off value of 1.5 in the same population, that would mean that four invasive aspergillosis patients would be missed (sensitivity 61%, 39% false negatives), and six patients would be treated or referred for further testing unnecessarily (specificity 93%, 7% false negatives). These numbers should, however, be interpreted with caution because the results were very heterogeneous. | The authors of this systematic review found 54 studies that looked at the error rates of this galactomannan test. These studies compared the results of the galactomannan test with the results of a more elaborate diagnostic workup, so that the percentages of false positive results (patients without invasive aspergillosis, according to the elaborate testing, but with a positive galactomannan test) and false negative results (patients with invasive aspergillosis, according to the elaborate testing, but with a negative galactomannan test) could be calculated. The galactomannan test does not result in a yes/no answer, but in a so-called 'optical density index' (ODI). The authors of the different studies defined the galactomannan test as positive when the ODI was above 0.5, 1.0 or 1.5. Four studies used a different ODI and these were not included in the meta-analysis. Studies and results When an ODI of 0.5 or higher was said to be positive, the galactomannan test missed 22 out of every 100 patients with invasive aspergillosis and it resulted in a false positive test in 15 out of every 100 patients without invasive aspergillosis. When an ODI of 1.0 or higher was said to be positive, the galactomannan test missed 29 out of every 100 patients with invasive aspergillosis and it resulted in a false positive test in 10 out of every 100 patients without invasive aspergillosis. When an ODI of 1.5 or higher was said to be positive, the galactomannan test missed 37 out of every 100 patients with invasive aspergillosis and it resulted in a false positive test in only 7 out of every 100 patients without invasive aspergillosis. Limitations The studies showed variable results and had small numbers of patients with invasive aspergillosis. |
Twenty-three trials (1459 patients) fulfilled the selection criteria for this review. NSAIDs reduced creatinine clearance by 16 mL/min (95% CI 5 to 28) and potassium output by 38 mmol/day (95% CI 19 to 56) on the first day after surgery compared to placebo. There was no significant difference in serum creatinine on the first day (0 μmol/L, 95% CI -3 to 4) compared to placebo. No significant reduction in urine volume during the early postoperative period was found. There was no significant difference in serum creatinine in the early postoperative period between patients receiving diclofenac, ketorolac, indomethacin, ketoprofen or etodolac. No cases of postoperative renal failure requiring dialysis were described. The trials were not heterogeneous for the primary outcome. NSAIDs caused a clinically unimportant transient reduction in renal function in the early postoperative period in patients with normal preoperative renal function. NSAIDs should not be withheld from adults with normal preoperative renal function because of concerns about postoperative renal impairment. | The review of trials found that NSAIDs can cause small, temporary negative effects on the kidneys in adults, but no one in the trials experienced renal failure or serious kidney problems. These results may not apply to children or adults with decreased kidney function |
Forty-one trials involving more than 13,000 young people met our inclusion criteria (26 individually randomized controlled trials and 15 cluster-randomized trials). We judged the majority of studies to be at high or unclear risk of bias in at least one domain. Interventions were varied, with the majority adopting forms of individual or group counselling, with or without additional self-help materials to form complex interventions. Eight studies used primarily computer or messaging interventions, and four small studies used pharmacological interventions (nicotine patch or gum, or bupropion). There was evidence of an intervention effect for group counselling (9 studies, risk ratio (RR) 1.35, 95% confidence interval (CI) 1.03 to 1.77), but not for individual counselling (7 studies, RR 1.07, 95% CI 0.83 to 1.39), mixed delivery methods (8 studies, RR 1.26, 95% CI 0.95 to 1.66) or the computer or messaging interventions (pooled RRs between 0.79 and 1.18, 9 studies in total). There was no clear evidence for the effectiveness of pharmacological interventions, although confidence intervals were wide (nicotine replacement therapy 3 studies, RR 1.11, 95% CI 0.48 to 2.58; bupropion 1 study RR 1.49, 95% CI 0.55 to 4.02). No subgroup precluded the possibility of a clinically important effect. Studies of pharmacotherapies reported some adverse events considered related to study treatment, though most were mild, whereas no adverse events were reported in studies of behavioural interventions. Our certainty in the findings for all comparisons is low or very low, mainly because of the clinical heterogeneity of the interventions, imprecision in the effect size estimates, and issues with risk of bias. There is limited evidence that either behavioural support or smoking cessation medication increases the proportion of young people that stop smoking in the long-term. Findings are most promising for group-based behavioural interventions, but evidence remains limited for all intervention types. There continues to be a need for well-designed, adequately powered, randomized controlled trials of interventions for this population of smokers. | We identified 41 studies (around 13,000 participants) that researched ways of helping teenagers to quit smoking. These studies were of mixed quality and looked at various methods for stopping smoking, including one-to-one counselling, counselling as part of a group, methods using computers or text messaging, or a combination of these. Four studies used drug treatments such as nicotine patches. Most studies recruited participants from schools, and 29 of the studies were carried out in North America. Although some programmes showed promise, especially those that used group counselling and those that combined a variety of approaches, there was no strong evidence that any particular method was effective in helping young people to stop smoking. Trials differed in how they measured whether a person had quit smoking, and many trials did not have enough participants for us to be confident about wider application of the results. Medications such as nicotine replacement and bupropion were not shown to be successful with adolescents, and some adverse events were reported, although these events were generally mild and findings were based on studies with small numbers of participants. Based on these findings we cannot currently identify a programme for helping adolescents to stop smoking that is more successful than trying to stop unaided. The quality of evidence was low or very low for all of the outcomes in this review. This is because of issues with the quality of some of the studies, the small number of studies and participants for some outcomes, and the differences between the studies. |
Three studies with 606 participants compared mirtazapine with placebo (but not other drugs) over seven to 13 weeks. Two studies were at unclear or high risk of bias in six or seven of eight domains. We judged the evidence for all outcomes to be low- or very low-quality because of poor study quality, indirectness, imprecision, risk of publication bias, and sometimes low numbers of events. There was no difference between mirtazapine and placebo for any primary outcome: participant-reported pain relief of 50% or greater (22% versus 16%; RD 0.05, 95% confidence interval (CI) -0.01 to 0.12; three studies with 591 participants; low-quality evidence); no data available for PGIC; only a single serious adverse event for evaluation of safety (RD -0.00, 95% CI -0.01 to 0.02; three studies with 606 participants; very low-quality evidence); and tolerability as frequency of dropouts due to adverse events (3% versus 2%; RD 0.00, 95% CI -0.02 to 0.03; three studies with 606 participants; low-quality evidence). Mirtazapine showed a clinically-relevant benefit compared to placebo for some secondary outcomes: participant-reported pain relief of 30% or greater (47% versus 34%; RD 0.13, 95% CI 0.05 to 0.21; number needed to treat for an additional beneficial outcome (NNTB) 8, 95% CI 5 to 20; three studies with 591 participants; low-quality evidence); participant-reported mean pain intensity (SMD -0.29, 95% CI -0.46 to -0.13; three studies with 591 participants; low-quality evidence); and participant-reported sleep problems (SMD -0.23, 95% CI -0.39 to -0.06; three studies with 573 participants; low-quality evidence). There was no benefit for improvement of participant-reported improvement of HRQoL of 20% or greater (58% versus 50%; RD 0.08, 95% CI -0.01 to 0.16; three studies with 586 participants; low-quality evidence); participant-reported fatigue (SMD -0.02, 95% CI -0.19 to 0.16; two studies with 533 participants; low-quality evidence); participant-reported negative mood (SMD -0.67, 95% CI -1.44 to 0.10; three studies with 588 participants; low-quality evidence); or withdrawals due to lack of efficacy (1.5% versus 0.1%; RD 0.01, 95% CI -0.01 to 0.02; three studies with 605 participants; very low-quality evidence). There was no difference between mirtazapine and placebo for participants reporting any adverse event (76% versus 59%; RD 0.12, 95 CI -0.01 to 0.26; three studies with 606 participants; low-quality evidence). There was a clinically-relevant harm with mirtazapine compared to placebo: in the number of participants with somnolence (42% versus 14%; RD 0.24, 95% CI 0.18 to 0.30; number needed to treat for an additional harmful outcome (NNTH) 5, 95% CI 3 to 6; three studies with 606 participants; low-quality evidence); weight gain (19% versus 1%; RD 0.17, 95% CI 0.11 to 0.23; NNTH 6, 95% CI 5 to 10; three studies with 606 participants; low-quality evidence); and elevated alanine aminotransferase (13% versus 2%; RD 0.13, 95% CI 0.04 to 0.22; NNTH 8, 95% CI 5 to 25; two studies with 566 participants; low-quality evidence). Studies demonstrated no benefit of mirtazapine over placebo for pain relief of 50% or greater, PGIC, improvement of HRQoL of 20% or greater, or reduction of fatigue or negative mood. Clinically-relevant benefits were shown for pain relief of 30% or greater, reduction of mean pain intensity, and sleep problems. Somnolence, weight gain, and elevated alanine aminotransferase were more frequent with mirtazapine than placebo. The quality of evidence was low or very low, with two of three studies of questionable quality and issues over indirectness and risk of publication bias. On balance, any potential benefits of mirtazapine in fibromyalgia were outweighed by its potential harms, though, a small minority of people with fibromyalgia might experience substantial symptom relief without clinically-relevant adverse events. | In July 2018 we searched for clinical trials where mirtazapine was used to treat fibromyalgia in adults. We found three studies with 606 participants. Studies were seven to 13 weeks long. They compared mirtazapine 15 mg to 45 mg daily against a fake medication (placebo). There was no difference between mirtazapine and placebo for any primary outcome: mirtazapine and placebo reduced pain by 50% in two of 10 people (low-quality evidence). Only one single serious adverse event was available for evaluation of safety (very low-quality evidence). Three of 10 participants with mirtazapine and two of 10 participants with placebo dropped out of the trial due to side effects (low-quality evidence). Mirtazapine reduced pain by 30% or more in five out of 10 people, compared with three out of 10 with placebo (low-quality evidence). It was also better for average pain intensity (low-quality evidence) and sleep problems (low-quality evidence). Mirtazapine was not better than placebo in reducing fatigue, depression, or improving health-related quality of life (low-quality evidence). Mirtazapine and placebo were no different in how many participants experienced a side effect (low-quality evidence). People dropped out at the same rate with mirtazapine and placebo or because they felt the drug did not work (low-quality evidence). For some side effects, mirtazapine was worse than placebo. This was true for drowsiness (4 out of 10 with mirtazapine, 1 out of 10 with placebo), weight gain (2 out of 10 with mirtazapine, 0 out of 10 with placebo), and high liver enzymes (1 out of 10 with mirtazapine, 0 out of 10 with placebo) (low-quality evidence). Two of the studies were of poor quality. We rated the quality of the evidence 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 judged that the evidence was mostly of low-quality, which means that while the research provides some indication of the likely effect, the true effect may be substantially different. The main issues were poor study quality, decisions about the types of people included in the studies, risk of important information not being published, and sometimes low numbers of events. |
We added four studies for the 2019 update. The review now includes 38 trials, recruiting a total of 10,377 participants. Studies lasted between two months and three years and investigated a range of mucolytics, including N-acetylcysteine, carbocysteine, erdosteine, and ambroxol, given at least once daily. Many studies did not clearly describe allocation concealment, and we had concerns about blinding and high levels of attrition in some studies. The primary outcomes were exacerbations and number of days of disability. Results of 28 studies including 6723 participants show that receiving mucolytics may be more likely to be exacerbation-free during the study period compared to those given placebo (Peto odds ratio (OR) 1.73, 95% confidence interval (CI) 1.56 to 1.91; moderate-certainty evidence). However, more recent studies show less benefit of treatment than was reported in earlier studies in this review. The overall number needed to treat with mucolytics for an average of nine months to keep an additional participant free from exacerbations was eight (NNTB 8, 95% CI 7 to 10). High heterogeneity was noted for this outcome (I² = 62%), so results need to be interpreted with caution. The type or dose of mucolytic did not seem to alter the effect size, nor did the severity of COPD, including exacerbation history. Longer studies showed smaller effects of mucolytics than were reported in shorter studies. Mucolytic use was associated with a reduction of 0.43 days of disability per participant per month compared with use of placebo (95% CI -0.56 to -0.30; studies = 9; I² = 61%; moderate-certainty evidence). With mucolytics, the number of people with one or more hospitalisations was reduced, but study results were not consistent (Peto OR 0.68, 95% CI 0.52 to 0.89; participants = 1788; studies = 4; I² = 58%; moderate-certainty evidence). Investigators reported improved quality of life with mucolytics (mean difference (MD) -1.37, 95% CI -2.85 to 0.11; participants = 2721; studies = 7; I² = 64%; moderate-certainty evidence). However, the mean difference did not reach the minimal clinically important difference of -4 units, and the confidence interval includes no difference. Mucolytic treatment was associated with a possible reduction in adverse events (OR 0.84, 95% CI 0.74 to 0.94; participants = 7264; studies = 24; I² = 46%; moderate-certainty evidence), but the pooled effect includes no difference if a random-effects model is used. Several studies that could not be included in the meta-analysis reported high numbers of adverse events, up to a mean of five events per person during follow-up. There was no clear difference between mucolytics and placebo for mortality, but the confidence interval is too wide to confirm that treatment has no effect on mortality (Peto OR 0.98, 95% CI 0.51 to 1.87; participants = 3527; studies = 11; I² = 0%; moderate-certainty evidence). In participants with chronic bronchitis or COPD, we are moderately confident that treatment with mucolytics leads to a small reduction in the likelihood of having an acute exacerbation, in days of disability per month and possibly hospitalisations, but is not associated with an increase in adverse events. There appears to be limited impact on lung function or health-related quality of life. Results are too imprecise to be certain whether or not there is an effect on mortality. Our confidence in the results is reduced by high levels of heterogeneity in many of the outcomes and the fact that effects on exacerbations shown in early trials were larger than those reported by more recent studies. This may be a result of greater risk of selection or publication bias in earlier trials, thus benefits of treatment may not be as great as was suggested by previous evidence. | We looked for studies lasting at least two months, in which it was decided at random whether a person received a mucolytic drug or a placebo. We did not include studies involving children or people with other breathing conditions such as asthma and cystic fibrosis. We found 38 studies to include in our review. These studies included a total of 10,377 adults with COPD or chronic bronchitis. The studies used a variety of mucolytic drugs, including N-acetylcysteine, carbocysteine, and erdosteine and lasted from two months to three years. Mucolytics were taken by mouth between one and three times per day. These studies measured several different outcomes to find out if the drug was useful, including flare-ups, hospital admissions, quality of life, lung function, and side effects. We found that people taking mucolytic drugs were less likely to experience a flare-up compared to those taking placebo. Approximately eight people would need to take the drug for nine months for one extra person to avoid having a flare-up. This result was based on 28 studies involving 6723 people. However, the studies carried out a longer time ago (1970s to 1990s) show greater benefit than those carried out more recently. Shorter studies also seemed to show more benefit than longer studies. This could be because the newer trials were larger and may be showing that mucolytics are less beneficial than the earlier studies showed. Or it could be that only studies that showed mucolytics as beneficial were published before the 2000s, when there was a push to report all trial results regardless of whether or not they showed benefit. People taking mucolytics had fewer days of disability (i.e. days when they could not do their normal activities) every month, but this was quite a small difference - less than half a day per person per month. They were also approximately one-third less likely to be admitted to hospital, although this result is based on only five studies that provided this information. Study results suggest that mucolytics do not have an important impact on quality of life or lung function. People taking mucolytics did not experience more unwanted side effects than those taking placebo. But we could not be sure about their impact on death during the study period because only 37 deaths occurred amongst the 3527 participants in studies where deaths were measured and reported. We are moderately confident about the results we have presented. Our confidence is reduced by the results from individual studies looking quite different from one another and the mix of older and newer studies that we found. Also, in some cases there were not enough data to be sure whether mucolytics were better or worse than, or the same as, placebo. Mucolytics appear to be useful for reducing flare-ups, days of disability, and hospital admissions in people with COPD or chronic bronchitis, and they do not appear to cause more side effects. However, they do not appear to have much impact on quality of life or lung function, and we could not be sure about their impact on death. This plain language summary is current to April 2019. |
We identified five RCTs with 11,466 participants that fulfilled the inclusion criteria. There were 18 cases of invasive cervical cancer, seven in the immediate colposcopy and 11 in the cytological surveillance groups, respectively. Although immediate colposcopy detects CIN2+ and CIN3+ earlier than cytology, the differences were no longer observed at 24 months (CIN2+: 3 studies, 4331 women; 17.9% versus 18.3%, RR 1.14, CI 0.66 to 1.97; CIN3+: 3 studies, 4331 women; 10.3% versus 11.9%, RR 1.02, CI 0.53 to 1.97). The inter-study heterogeneity was considerable (I2 greater than 90%). Furthermore, the inclusion of the results of the exit examinations at 24 months, which could inflate the CIN detection rate of cytological surveillance, may have led to study design-derived bias; we therefore considered the evidence to be of low quality. When we excluded the exit examination, the detection rate of high-grade lesions at the 18-month follow-up was higher after immediate colposcopy (CIN2+: 2 studies, 4028 women; 14.3% versus 10.1%, RR 1.50, CI 1.12 to 2.01; CIN3+: 2 studies, 4028 women, 7.8% versus 6.9%, RR 1.24, CI 0.77 to 1.98) both had substantial inter-study heterogeneity (I2 greater than 60%) and we considered the evidence to be of moderate quality). The meta-analysis revealed that immediate referral to colposcopy significantly increased the detection of clinically insignificant cervical abnormalities, as opposed to repeat cytology after 24 months of surveillance (occurrence of koilocytosis: 2 studies, 656 women; 32% versus 21%, RR 1.49, 95% CI 1.17 to 1.90; moderate-quality evidence) incidence of any CIN: 2 studies, 656 women; 64% versus 32%, RR 2.02, 95% CI 1.33 to 3.08, low-quality evidence; incidence of CIN1: 2 studies, 656 women; 21% versus 8%, RR 2.58, 95% CI 1.69 to 3.94, moderate-quality evidence). Due to differences in trial designs and settings, there was large variation in default rates between the included studies. The risk for default was higher for the repeat cytology group, with a four-fold increase at 6 months, a six-fold at 12 and a 19-fold at 24 months (6 months: 3 studies, 5117 women; 6.3% versus 13.3%, RR 3.85, 95% CI 1.27 to 11.63, moderate-quality evidence; 12 months: 3 studies, 5115 women; 6.3% versus 14.8%, RR 6.39, 95% CI 1.49 to 29.29, moderate-quality evidence; 24 months: 3 studies, 4331 women; 0.9% versus 16.1%, RR 19.1, 95% CI 9.02 to 40.43, moderate-quality evidence). Based on low- or moderate-quality evidence using the GRADE approach and generally low risk of bias, the detection rate of CIN2+ or CIN3+ after two years does not appear to differ between immediate colposcopy and cytological surveillance in the absence of HPV testing, although women may default from follow-up. Immediate colposcopy probably leads to earlier detection of high-grade lesions, but also detects more clinically insignificant low-grade lesions. Colposcopy may therefore be the first choice when good compliance is not assured. These results emphasize the need for an accurate reflex HPV triage test to distinguish women who need diagnostic follow-up from those who can return safely to routine recall. | We included 5 randomised controlled trials including 11,466 participants with minor abnormalities on cervical cytology, treated either with immediate colposcopy or repetitive cytology. The included studies assessed differences in occurrence of cervical precancerous lesions between the two treatments. The results suggested that women attending immediate colposcopy after a single low-grade abnormal cervical cytology test were more likely to have clinically insignificant findings detected than women who were managed with 'watchful waiting'. There were 18 cases of invasive cervical cancer, seven in the immediate colposcopy and 11 in the cytological surveillance groups. The detection rate of clinically insignificant low-grade lesions was higher in the immediate colposcopy group, as was the detection rate of clinically more significant high-grade precancerous lesions (CIN2 or CIN2 or worse) at 18 months, but not by 24 months. The risk of non-compliance was significantly greater for the repeat cytology arm and increased with the length of the follow-up. We graded the evidence as low to moderate quality. HPV DNA testing has been shown to be an effective triage tool for women with minor cervical cytology abnormalities. However, this test is not currently routinely available globally. Therefore, if HPV DNA testing is not available, immediate colposcopy is likely to detect more precancerous lesions earlier than cytological surveillance, but after two years there does not seem to be a difference between the two approaches. Women could be referred for immediate colposcopy after a single low-grade abnormal or borderline cervical cytology test, if compliance with cytological surveillance is expected to be poor. When follow-up compliance is expected to be good, repeat cervical cytology may be offered, as this may reduce the risk of over-diagnosis and over-treatment. |
We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with in-hospital thromoprophylaxis followed by placebo or no thromboprophylaxis after discharge. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria. For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I2 = 28%; moderate-quality evidence). For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I2 = 28%; moderate-quality evidence). We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I2 = 0%; moderate-quality evidence). The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis, which approached significance (M-H OR 0.30, 95% CI 0.08 to 1.11; I2 = 0%; moderate-quality evidence). No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (M-H OR 1.10, 95% CI 0.67 to 1.81; I2 = 0%; moderate-quality evidence). No difference in mortality between the control and LMWH group was found, 3.8% and 3.9%, respectively (M-H OR 1.15, 95% CI 0.72 to 1.84; moderate-quality evidence). Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review. | Seven studies were found that addressed this question, including a total of 1728 patients. Continuing blood thinning injections after hospital discharge decreased the risk of both blood clots in the limbs and in the lungs. This review determined that the overall incidence of having a blood clot is reduced from 13.2%, when no post-discharge blood thinner injections are used, to 5.3% when a blood thinner injection is prescribed for at least 14 days following discharge in 30 days follow-up. Both symptomatic and asymptomatic blood clots decreased with the use of prolonged duration blood thinner injections in postoperative patients. No increase in bleeding complications or death, common concerns when blood thinners are used, were observed in patients treated with prolonged duration blood thinner injections. Continuation of blood thinning injections for at least 14 days after abdominal or pelvic surgery reduces the risk of blood clots. |
We identified five randomised clinical trials with 290 patients. All trials were considered to have high risk of bias. Patients in the experimental group received compound phyllanthus for three months to 12 months. Patients in the antiviral drug group received lamivudine, interferon alpha, thymosin, or thymosin alpha 1. None of the trials reported mortality, hepatitis B-related morbidity, quality of life, or liver histology. Phyllanthus seemed to have a superior effect on clearance of serum HBeAg at the end of treatment in conventional meta-analysis (RR 0.76; 95% CI 0.64 to 0.91, P = 0.002; I2 = 0%), but not when trial sequential analysis was applied. Phyllanthus had no significant effect on clearance of serum HBsAg (RR 1.00; 95% CI 0.93 to 1.08, P = 0.92; I2 = 0%) or HBV DNA (RR 0.83; 95% CI 0.53 to 1.31, P = 0.43; I2 = 70%) when compared with antiviral drugs. Data on HBeAg seroconversion was reported in one trial and no significant difference was found comparing phyllanthus versus lamivudine (RR 0.89; 95% CI 0.71 to 1.11). No data were reported on adverse events in the five trials. There is currently insufficient evidence to support or refute the use of phyllanthus for patients with chronic hepatitis B virus infection. Researchers who are interested in conducting further randomised clinical trials on phyllanthus ought to monitor both beneficial and harmful effects and should primarily test the herb against placebo in addition to antiviral drugs that are known to offer more benefit than harm. Only in this way new interventions can be assessed without compromising personal ethical considerations. | The findings of this review are based on five randomised clinical trials with 290 patients. Phyllanthus was tested versus antiviral drugs, including lamivudine, interferon alpha, thymosin, or thymosin alpha 1 for three months to 12 months. The primary findings of this review are that phyllanthus seemed to have a superior effect on clearance of serum HBeAg at the end of treatment in conventional meta-analysis, but not when trial sequential analysis was applied. Phyllanthus had no significant effect on clearance of serum HBsAg, serum HBV DNA, or HBeAg seroconversion when compared with antiviral drugs. No data were identified on mortality or morbidity, adverse events, quality of life, or liver histology. However, the findings in our review are inconclusive due to the small numbers of patients and outcomes, risk of bias, and the study design. We need more randomised trials to confirm or reject the potential effects of phyllanthus. We advocate that phyllanthus is primarily assessed against placebo. This can be done in randomised clinical trials in which all patients receive antiviral drugs that are known to offer more benefit than harm and the patients are then randomised to phyllanthus versus placebo. If the effect of phyllanthus versus placebo is unequivocally demonstrated in such trials, it may be prudent to assess the effects of phyllanthus versus other antiviral drugs superior to placebo in such trials. The quality of trials regarding conduct and report should also be taken into account. |
Of the 1125 records screened for eligibility, four RCTs (N = 201 participants), and one on-going study, met the inclusion criteria. Two classes of antidepressants were investigated in two separate comparisons with placebo: a tricyclic antidepressant (TCA) and selective serotonin reuptake inhibitors (SSRIs). TCA versus placebo Only one RCT (N = 30 participants) provided results for this comparison. Primary outcomes The TCA (nortriptyline) reduced depressive symptoms post-treatment compared to placebo (MD -10.20, 95% CI -16.75 to -3.65; P = 0.007; very low-quality evidence), as measured by the Hamilton Depression Rating Scale (HAM-D). Three participants withdrew from the trial due to adverse events related to the tested antidepressant (dry mouth, sedation, orthostatic hypotension). Secondary outcomes The overall results post-treatment indicated that nortriptyline was not effective in improving the quality of life of individuals with COPD, as measured by the Sickness Impact Profile (MD -2.80, 95% CI -11.02 to 5.42; P = 0.50; very low-quality evidence). The results for the change in dyspnoea for the domains examined (e.g. dyspnoea scores for 'most day-to-day activities') post-treatment showed no improvement in the intervention group (MD 9.80, 95% CI -6.20 to 25.80; P = 0.23; very low-quality evidence). No data were reported for change in FEV1, change in exercise tolerance, change in hospital utilisation, or cost-effectiveness. The TCA study provided short-term results, with the last follow-up data collection at 12 weeks. The quality of the evidence for all the outcomes evaluated was very low due to a small sample size, imprecision, attrition, and selection and reporting bias. SSRIs versus placebo Three RCTs (N = 171 participants) provided results for this comparison. Primary outcomes The pooled results for two studies showed no difference for the change in depressive symptoms post-intervention (SMD 0.75, 95% CI -1.14 to 2.64; 148 participants; 2 studies; P = 0.44; very low-quality evidence). High heterogeneity was observed (I² = 95%), limiting the reliability of these findings. While it was not possible to meta-analyse the total adverse events rates across the studies, it was possible to combine the results for two medication-specific adverse effects: nausea and dizziness. There were no significant post-treatment group differences for nausea (OR 2.32, 95% CI 0.66 to 8.12; 171 participants; 3 studies; P = 0.19; very low-quality evidence) or dizziness (OR 0.61, 95% CI 0.09 to 4.06; 143 participants; 2 studies; P = 0.61; very low-quality evidence). Secondary outcomes The pooled analysis of two trials reporting data for the change in quality of life did not show improvement post-treatment in the intervention group compared to placebo (SMD 1.17, 95% CI -0.80 to 3.15; 148 participants; 2 studies; P = 0.25; very low-quality evidence). There was no difference between groups in change in FEV1 post-treatment (MD 0.01, 95% CI -0.03 to 0.05; 148 participants; 2 studies; P = 0.60; low-quality evidence). However, two trials reported improvement in exercise tolerance in the SSRI group versus the placebo group (MD 13.88, 95% CI 11.73 to 16.03; 148 participants; 2 studies; P < 0.001; very low-quality evidence). The trials included in this comparison did not report data related to the change in dyspnoea, hospital utilisation rates, or cost-effectiveness. There is insufficient evidence to make definitive statements about the efficacy or safety of antidepressants for treating COPD-related depression. New RCTs are needed; with better methodological quality and more accurate reporting of the methods used. Moreover, longer-term follow-up data collection is needed, including outcomes such as adverse events, hospital utilisation and cost-effectiveness. | This review included experimental studies called randomised controlled trials (studies in which participants are assigned to a treatment group based on a random method) that compared the effectiveness of pharmacological interventions (antidepressants) to placebo (inactive treatment in the same form as the active treatment, e.g. a pill). Study participants were adults diagnosed with COPD and depression. What does the evidence from the review tell us? We have identified only four studies worldwide that were eligible for inclusion in our review. This means limited evidence to support the use of antidepressants for the treatment of depression in patients with COPD. Only one study evaluated a tricyclic antidepressant, nortriptyline, finding that it reduced depressive symptoms when compared to a placebo. Three studies evaluated a newer generation class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), finding no evidence for their effectiveness in improving depressive symptoms. Due to the limited evidence, we are unable to make definitive statements about the effectiveness but also safety of antidepressants when used for COPD-related depression. However, SSRIs may increase exercise capacity in patients with COPD. Given that the current findings were based on only four small studies with evidence rated as of very low quality, it is important to interpret our results with caution. What should happen next? Insufficient evidence prevented us from making clear recommendations for doctors, other healthcare professionals, researchers, or policymakers. More studies with better methodological quality and a larger number of participants are needed. |
We identified 3745 citations through electronic searches and reviews of reference lists after deduplication of search results. We excluded 3619 records during title and abstract review and assessed 126 articles at full-text review for eligibility. We included one controlled study enrolling 46 participants. We rated this RCT at high risk for performance and detection bias due to a lack of blinding. The included RCT compared preventive use of mindfulness-based cognitive therapy (MBCT) with treatment as usual (TAU) in participants with a history of SAD. MBCT was administered in spring in eight weekly individual 45- to 60-minute sessions. In the TAU group participants did not receive any preventive treatment but were invited to start light therapy as first depressive symptoms occurred. Both groups were assessed weekly for occurrence of a new depressive episode measured with the Inventory of Depressive Syptomatology-Self-Report (IDS-SR, range 0-90) from September 2011 to mid-April 2012. The incidence of a new depressive episode in the upcoming winter was similar in both groups. In the MBCT group 65% of 23 participants developed depression (IDS-SR ≥ 20), compared to 74% of 23 people in the TAU group (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.60 to 1.30; 46 participants; very low quality-evidence). For participants with depressive episodes, severity of depression was comparable between groups. Participants in the MBCT group had a mean score of 26.5 (SD 7.0) on the IDS-SR, and TAU participants a mean score of 25.3 (SD 6.3) (mean difference (MD) 1.20, 95% CI -3.44 to 5.84; 32 participants; very low quality-evidence). The overall discontinuation rate was similar too, with 17% discontinuing in the MBCT group and 13% in the TAU group (RR 1.33, 95% CI 0.34 to 5.30; 46 participants; very low quality-evidence). Reasons for downgrading the quality of evidence included high risk of bias of the included study and imprecision. Investigators provided no information on adverse events. We could not find any studies that compared psychological therapy with other interventions of interest such as second-generation antidepressants, light therapy, melatonin or agomelatine. The evidence on psychological therapies to prevent the onset of a new depressive episode in people with a history of SAD is inconclusive. We identified only one study including 46 participants focusing on one type of psychological therapy. Methodological limitations and the small sample size preclude us from drawing a conclusion on benefits and harms of MBCT as a preventive intervention for SAD. Given that there is no comparative evidence for psychological therapy versus other preventive options, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences and other preventive interventions that are supported by evidence. | The proportion of participants developing a depression in the upcoming winter was similar in both groups as well as the severity of these depressive episodes. However, the quality of the evidence was very low, so we can draw no valid conclusion if MBCT is really ineffective in preventing SAD or not. The included study reported no information on side effects of the intervention. Doctors need to discuss with patients the advantages and disadvantages of MBCT and other potentially preventive treatments for winter depression, such as other psychological therapies, drug treatments, or lifestyle interventions. As no available studies have compared these treatments, treatment selection should be strongly based on patient preferences and other preventive interventions that are supported by evidence. Review authors recommend that future studies should evaluate the efficacy of different psychological therapies in preventing SAD in larger study samples and should directly compare these interventions versus other preventive treatments, such as light therapy, antidepressants and agomelatine, to determine the best treatment option for prevention of SAD. |
The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine had a higher attrition rate due to adverse effects than olanzapine (9 RCTs, n=1674, RR 1.60 CI 1.07 to 2.40, NNT 25 CI 15 to 73) and risperidone (6 RCTs, n=627, RR 1.88 CI 1.11 to 3.21, NNT 16 CI 9 to 59). Fewer participants in the clozapine groups left the trials early due to inefficacy than risperidone (6 RCTs, n=627, RR 0.40 CI 0.23 to 0.70, NNT 11 CI 7 to 21), suggesting a certain higher efficacy of clozapine. Clozapine was more efficacious than zotepine in improving the participants general mental state (BPRS total score: 1 RCT, n=59, MD -6.00 CI -9.83 to -2.17), but not consistently more than olanzapine, quetiapine, risperidone and ziprasidone. There was no significant difference between clozapine and olanzapine or risperidone in terms of positive or negative symptoms of schizophrenia. According to two studies from China quetiapine was more efficacious for negative symptoms than clozapine (2 RCTs, n=142, MD 2.23 CI 0.99 to 3.48). Clozapine produced somewhat fewer extrapyramidal side-effects than risperidone (use of antiparkinson medication: 6 RCTs, n=304, RR 0.39 CI 0.22 to 0.68, NNT 7 CI 5 to 18) and zotepine (n=59, RR 0.05 CI 0.00 to 0.86, NNT 3 CI 2 to 5). More participants in the clozapine group showed decreased white blood cells than those taking olanzapine, more hypersalivation and sedation than those on olanzapine, risperidone and quetiapine and more seizures than people on olanzapine and risperidone. Also clozapine produced an important weight gain not seen with risperidone. Other differences in adverse effects were less documented and should be replicated, for example, clozapine did not alter prolactin levels whereas olanzapine, risperidone and zotepine did; compared with quetiapine, clozapine produced a higher incidence of electrocardiogram (ECG) alterations; and compared with quetiapine and risperidone clozapine produced a higher increase of triglyceride levels. Other findings that should be replicated were: clozapine improved social functioning less than risperidone and fewer participants in the clozapine group had to be hospitalised to avoid suicide attempts compared to olanzapine. Other important outcomes such as service use, cognitive functioning, satisfaction with care or quality of life were rarely reported. Clozapine may be a little more efficacious than zotepine and risperidone but further trials are required to confirm this finding. Clozapine differs more clearly in adverse effects from other second generation antipsychotics and the side-effect profile could be key in the selection of treatment depending on the clinical situation and a patient’s preferences. Data on other important outcomes such as cognitive functioning, quality of life, death or service use are currently largely missing, making further large and well-designed trials necessary. It is also important to take into account that the large number of people leaving the studies early limits the validity and interpretation of our findings. | This review compared the clinical effects of clozapine with the other atypical antipsychotics. Twenty-seven studies fulfilled the review's criteria and provided data to compare clozapine with antipsychotics such as olanzapine, quetiapine, risperidone, ziprasidone and zotepine. Clozapine was somewhat more efficacious than zotepine. Also, inefficacy of treatment led more frequently to leaving the studies early in the risperidone group suggesting a certain higher efficacy of clozapine. The principal drawback of clozapine were its adverse effects which lead to significantly higher numbers of participants leaving the studies early compared to olanzapine and risperidone. Clozapine was associated with more sedation and hypersalivation than olanzapine, quetiapine and risperidone and with more seizures than olanzapine and risperidone. There was a higher incidence of white blood cell decrease in clozapine groups than olanzapine and more weight gain than in risperidone groups. On the other hand clozapine produced fewer movement disorder than risperidone and less prolactin increase than olanzapine, quetiapine and zotepine. |
In this review update, we added one study with 219 children. A total of two RCTs with 249 children (n = 240 completed) were eligible for inclusion in this review. Both studies contributed to our primary and secondary outcomes, but we assessed the quality of evidence for our three primary outcomes as low, owing to the small numbers of studies and participants; and high attrition in one of the studies. Data show no significant differences between treatment groups for our primary outcomes: proportion of children (n = 249) who had persistent symptoms at follow-up (odds ratio (OR) 0.69, 95% confidence interval (CI) 0.37 to 1.28; fixed-effect model); and number of children (n = 240) rehospitalised with respiratory illness within six months (OR 0.54, 95% CI 0.05 to 6.21; random-effects model). We were unable to analyse exacerbation rate because studies used different methods to report this information. Data showed no significant differences between treatment groups for our secondary outcome: proportion of children (n = 240) with wheeze at six months (OR 0.47, 95% CI 0.06 to 3.95; random-effects model). One study reported bacterial resistance, but only at 48 hours (thus with limited applicability for this review). Another study reported adverse events from which all children recovered and remained in the study. Current evidence is insufficient to inform whether antibiotics should be used to treat or prevent persistent respiratory symptoms in the post-acute bronchiolitis phase. Future RCTs are needed to evaluate the efficacy of antibiotics for reducing persistent respiratory symptoms. This is particularly important in populations with high acute and post-acute bronchiolitis morbidity (e.g. indigenous populations in Australia, New Zealand, and the USA). | This review update (up to 26 August 2016) includes two clinical trials that compared antibiotics with placebo for children in the post-acute bronchiolitis phase (> 14 days). The first was reported from Turkey and enrolled 30 infants aged seven months or younger. The second was reported from Australia and New Zealand and enrolled 249 infants aged 24 months or younger. Both trials initiated treatment during hospitalisation for bronchiolitis and provided follow-up for six months post hospitalisation. This review update includes a total of two trials with 249 children (n = 240 completed). Both studies contributed to primary and secondary outcomes, but the quality of evidence was low. Review authors noted no significant differences between treatment groups for our primary outcomes: proportion of children (n = 249) who had persistent symptoms at follow-up, and number of children (n = 240) rehospitalised with respiratory illness within six months; nor for our secondary outcome: proportion of children (n = 240) with wheeze at six months. One study reported bacterial resistance, but only at 48 hours. One study reported adverse events from which all children recovered and remained in the study. Currently, not enough evidence is available to inform whether antibiotics should be used to treat or prevent persistent respiratory symptoms in the post-acute phase of bronchiolitis. Clinical trials are needed to evaluate the efficacy of antibiotics for reducing persistent respiratory symptoms, especially in countries where morbidity of bronchiolitis is high (e.g. indigenous populations). |
Six studies (477 participants) were included in the review. All participants were adult kidney transplant recipients and 70% of participants underwent live-donor kidney transplantation. The overall risk of bias was low for selection bias and unclear for remaining domains. There was no difference in the risk of delayed graft function (3 studies, 298 participants: RR 1.03, 95% CI 0.62 to 1.70) or hyperkalaemia (2 studies, 199 participants: RR 0.48, 95% CI 0.04 to 6.10) for participants who received balanced electrolyte solutions compared to normal saline. Intraoperative balanced electrolyte solutions compared to normal saline were associated with higher blood pH (3 studies, 193 participants: MD 0.07, 95% CI 0.05 to 0.09), higher serum bicarbonate (3 studies, 215 participants: MD 3.02 mEq/L, 95% CI 2.00 to 4.05) and lower serum chloride (3 studies, 215 participants: MD -9.93 mmol/L, 95% CI -19.96 to 0.11). There were four cases of graft loss in the normal saline group and one in the balanced electrolyte solution group, and four cases of acute rejection in the normal saline group compared to two cases in the balanced electrolyte solution group. Balanced electrolyte solutions are associated with less hyperchloraemic metabolic acidosis compared to normal saline, however it remains uncertain whether lower-chloride solutions lead to improved graft outcomes compared to normal saline. | We found six studies that included 477 kidney transplant patients. The majority of these patients had a kidney transplant from a living donor. The overall quality of the studies was low to average, and the main problem was the small number of studies and the small size of the studies. There was no information on funding source for most of the studies. Compared to normal saline, giving kidney transplant patients solutions that contain less chloride during their transplant operation resulted in lower blood acid levels but did not affect how the transplant kidney worked after surgery, or the number of patients who had high blood potassium levels. Harmful effects were not reported in many studies. In the group of patients who were given lower-chloride fluids, the transplant failed in one patient and one patient rejected the transplant. In the group of patients who were given normal saline, the transplant failed in four patients, and two patients rejected the transplant. However, this is probably an incomplete picture of harmful effects. |
We included a total of 26 trials (3842 participants) in the review, and 23 trials (3693 participants) were included in one or more outcomes in the review. The vast majority of the participants underwent primary liver transplantation. All of the trials were at high risk of bias, and all of the evidence was of low or very low quality. In addition, because of sparse data involving trials at high risk of bias, it is not possible to entirely rely on the results of the network meta-analysis. The trials included mainly participants undergoing primary liver transplantation of varied aetiologies. The follow-up in the trials ranged from 3 to 144 months. The most common maintenance immunosuppression used as a control was tacrolimus. There was no evidence of difference in mortality (21 trials; 3492 participants) or graft loss (15 trials; 2961 participants) at maximal follow-up between the different maintenance immunosuppressive regimens based on the network meta-analysis. In the direct comparison, based on a single trial including 222 participants, tacrolimus plus sirolimus had increased mortality (HR 2.76, 95% CrI 1.30 to 6.69) and graft loss (HR 2.34, 95% CrI 1.28 to 4.61) at maximal follow-up compared with tacrolimus. There was no evidence of differences in the proportion of people with serious adverse events (1 trial; 719 participants), proportion of people with any adverse events (2 trials; 940 participants), renal impairment (8 trials; 2233 participants), chronic kidney disease (1 trial; 100 participants), graft rejections (any) (16 trials; 2726 participants), and graft rejections requiring treatment (5 trials; 1025 participants) between the different immunosuppressive regimens. The network meta-analysis showed that the number of adverse events was lower with cyclosporine A than with many other immunosuppressive regimens (12 trials; 1748 participants), and the risk of retransplantation (13 trials; 1994 participants) was higher with cyclosporine A than with tacrolimus (HR 3.08, 95% CrI 1.13 to 9.90). None of the trials reported number of serious adverse events, health-related quality of life, or costs. Funding: 14 trials were funded by pharmaceutical companies who would benefit from the results of the trial; two trials were funded by parties who had no vested interest in the results of the trial; and 10 trials did not report the source of funding. Based on low-quality evidence from a single small trial from direct comparison, tacrolimus plus sirolimus increases mortality and graft loss at maximal follow-up compared with tacrolimus. Based on very low-quality evidence from network meta-analysis, we found no evidence of difference between different immunosuppressive regimens. We found very low-quality evidence from network meta-analysis and low-quality evidence from direct comparison that cyclosporine A causes more retransplantation compared with tacrolimus. Future randomised clinical trials should be adequately powered; performed in people who are generally seen in the clinic rather than in highly selected participants; employ blinding; avoid postrandomisation dropouts or planned cross-overs; and use clinically important outcomes such as mortality, graft loss, renal impairment, chronic kidney disease, and retransplantation. Such trials should use tacrolimus as one of the control groups. Moreover, such trials ought to be designed in such a way as to ensure low risk of bias and low risks of random errors. | We identified 26 randomised clinical trials with a total of 3842 participants. Of these, 23 randomised clinical trials (3693 participants) provided information for one or more outcomes. The trials mainly included participants undergoing liver transplantation for the first time, for various reasons. Funding: 14 trials were funded by pharmaceutical companies who would benefit from the results of the trial; two trials were funded by parties who had no vested interest in the results of the trial; and 10 trials did not report the source of funding. The overall quality of the evidence was low or very low, and all of the trials were at high risk of bias, which means it is possible that the conclusions made could overestimate the benefits or underestimate the harms of a given intervention because of the way the trials were conducted. In addition, because of insufficient information, the results of network meta-analysis are not entirely reliable. Several medical drugs were compared in the trials. We found no evidence of difference in the risk of death or graft loss between the different immunosuppressive regimens based on the network meta-analysis. In the direct comparison, based on a single trial including 222 participants, the risk of death and graft loss was higher with tacrolimus plus sirolimus than with tacrolimus alone. There was no evidence of differences between the various immunosuppressive regimens in percentage of people who developed serious adverse events, percentage of people who developed any adverse events, risk of poor kidney function requiring dialysis or kidney transplantation (kidney dysfunction), prolonged kidney disease, graft rejections requiring treatment, and any graft rejections. The number of adverse events was lower with cyclosporine A than with many other immunosuppressive regimens. The risk of retransplantation was higher with cyclosporine A than with tacrolimus. None of the trials reported number of serious adverse events, health-related quality of life, or costs. There is significant uncertainty as to the optimal maintenance immunosuppressive regimen after liver transplantation; further well-designed randomised clinical trials are required. Future trials should be performed in people who are generally seen in the clinic rather than in highly selected participants and report clinically important outcomes such as death, graft loss, kidney dysfunction, long-term kidney disease, and retransplantation. Such trials should use tacrolimus as one of the control groups. Moreover, such trials ought to be designed in such a way as to ensure low risk of bias and low risks of random errors. |
Nine studies in dental, orthopedic and gynaecological surgery met the inclusion criteria, testing doses of diflunisal from 125 mg to 1000 mg. For diflunisal 1000 mg, the NNT for at least 50% pain relief over 4 to 6 hours was 2.1 (1.8 to 2.6) (6 studies, 391 participants); the NNT to prevent remedication within 6 hours was 1.9 (1.7 to 2.3), and within 12 hours was 2.2 (1.9 to 2.7) (6 studies, 409 participants). More participants experienced adverse events with diflunisal 100 mg than with placebo, but none were serious or led to withdrawal. For diflunisal 500 mg, the NNT for at least 50% pain relief over 4 to 6 hours was 2.6 (2.1 to 3.3) (6 studies, 357 participants); the NNT to prevent remedication within 6 hours was 2.6 (2.1 to 3.4) (6 studies, 390 participants), and within 12 hours was 2.9 (2.3 to 4.0) (5 studies, 329 participants). Adverse events did not differ significantly from placebo. Diflunisal has an analgesic effect similar to other NSAIDs in single dose, but benefits from providing significant analgesia for about twelve hours. This property may be useful when regular dosing is needed, or when taking several doses of a shorter acting analgesic is impractical. | This review assessed evidence from nine randomised, double-blind, placebo-controlled clinical trials, in which there were 906 adults in comparisons of diflunisal (a non-steroidal, anti-inflammatory drug) with placebo for treatment of moderate to severe acute post-operative pain. It is an effective analgesic over the dose range 250 mg to 1000 mg, with a long duration of action. At 1000 mg, the analgesic effect over 4 to 6 hours is as good as the combination of paracetamol 1000 mg and codeine 60 mg in similar studies using the same methods. |
We included in the meta-analysis 10 studies with 762 participants across one or more comparisons. The sample size of included studies ranged from 11 to 206 participants. Nine out of 10 studies involving all levels of COPD severity were conducted in China with adults from 55 to 88 years of age, a higher proportion of whom were male (78%). Nine out of 10 studies provided tai chi and/or qigong programmes as AMBMT, and one study provided yoga. Overall, the term 'PR' has been uncritically applied in the vast majority of studies, which limits comparison of AMBMT and PR. For example, eight out of 10 studies considered walking training as equal to PR and used this as conventional exercise training within PR. Overall study quality for main comparisons was moderate to very low mainly owing to imprecision, indirectness (exercise component inconsistent with recommendations), and risk of bias issues. The primary outcomes for our review were quality of life, dyspnoea, and serious adverse events. When researchers compared AMBMT versus PR alone (mainly unstructured walking training), statistically significant improvements in disease-specific quality of life (QoL) (St. George's Respiratory Questionnaire (SGRQ) total score) favoured AMBMT: mean difference (MD) -5.83, 95% confidence interval (CI) -8.75 to -2.92; three trials; 249 participants; low-quality evidence. The common effect size, but not the 95% CI around the pooled treatment effect, exceeded the minimal clinically important difference (MCID) of minus four. The COPD Assessment Test (CAT) also revealed statistically significant improvements favouring AMBMT over PR, with scores exceeding the MCID of three, with an MD of 6.58 units (95% CI -9.16 to – 4.00 units; one trial; 74 participants; low-quality evidence). Results show no between-group differences with regard to dyspnoea measured by the modified Medical Research Council Scale (MD 0.00 units, 95% CI -0.37 to 0.37; two trials; 127 participants; low-quality evidence), the Borg Scale (MD 0.44 units, 95% CI -0.88 to 0.00; one trial; 139 participants; low-quality evidence), or the Chronic Respiratory Questionnaire (CRQ) Dyspnoea Scale (MD -0.21, 95% CI -2.81 to 2.38; one trial; 11 participants; low-quality evidence). Comparisons of AMBMT versus PR alone did not include assessments of generic quality of life, adverse events, limb muscle function, exacerbations, or adherence. Comparisons of AMBMT added to PR versus PR alone (mainly unstructured walking training) revealed significant improvements in generic QoL as measured by Short Form (SF)-36 for both the SF-36 general health summary score (MD 5.42, 95% CI 3.82 to 7.02; one trial; 80 participants; very low-quality evidence) and the SF-36 mental health summary score (MD 3.29, 95% CI 1.45 to 4.95; one trial; 80 participants; very low-quality evidence). With regard to disease-specific QoL, investigators noted no significant improvement with addition of AMBMT to PR versus PR alone (SGRQ total score: MD -2.57, 95% CI -7.76 to 2.62 units; one trial; 192 participants; moderate-quality evidence; CRQ Dyspnoea Scale score: MD 0.04, 95% CI -2.18 to 2.26 units; one trial; 80 participants; very low-quality evidence). Comparisons of AMBMT + PR versus PR alone did not include assessments of dyspnoea, adverse events, limb muscle function, exacerbations, or adherence. Given the quality of available evidence, the effects of AMBMT versus PR or of AMBMT added to PR versus PR alone in people with stable COPD remain inconclusive. Evidence of low quality suggests better disease-specific QoL with AMBMT versus PR in people with stable COPD, and evidence of very low quality suggests no differences in dyspnoea between AMBMT and PR. Evidence of moderate quality shows that AMBMT added to PR does not result in improved disease-specific QoL, and evidence of very low quality suggests that AMBMT added to PR may lead to better generic QoL versus PR alone. Future studies with adequate descriptions of conventional exercise training (i.e. information on duration, intensity, and progression) delivered by trained professionals with a comprehensive understanding of respiratory physiology, exercise science, and the pathology of COPD are needed before definitive conclusions can be drawn regarding treatment outcomes with AMBMT versus PR or AMBMT added to PR versus PR alone for patients with COPD. | We included 10 studies involving 762 participants who were randomly assigned to receive AMBMT alone or in combination with PR or PR alone (mainly unstructured walking training). The quality of included studies was generally poor. Given the quality of available evidence, effects of AMBMT in comparison with PR or of AMBMT added to PR in comparison with PR alone remain inconclusive. One key reason for this is that PR programmes used as comparators had major design flaws, for example, the term 'PR' was uncritically used in the vast majority of studies, and PR was often considered equal to unstructured walking training. This, together with the poor quality of evidence, limits our confidence in the observed effects. Available evidence suggests that when AMBMT was compared to PR alone, larger improvements in disease-specific quality of life were observed with AMBMT, although AMBMT was not superior to PR with regard to dyspnoea (breathlessness). AMBMT added to PR resulted in large improvement in generic quality of life when compared with PR alone, although the addition of AMBMT to PR did not lead to further improvements in disease-specific quality of life. However, before definitive conclusions can be drawn, future research studies comparing AMBMT to PR are needed, and these should follow current PR guidelines for designing comparator interventions, preferably delivered by properly trained professionals with a comprehensive understanding of respiratory physiology, exercise science, and the pathology of COPD. |
We included 67 trials, involving 6300 participants. Fifty-one trials reported the primary outcome, a measure of activities of daily living. The estimated effects of physical rehabilitation at the end of the intervention were an improvement in Barthel Index (0 to 100) scores of six points (95% confidence interval (CI) 2 to 11, P = 0.008, seven studies), Functional Independence Measure (0 to 126) scores of five points (95% CI -2 to 12, P = 0.1, four studies), Rivermead Mobility Index (0 to 15) scores of 0.7 points (95% CI 0.04 to 1.3, P = 0.04, three studies), Timed Up and Go test of five seconds (95% CI -9 to 0, P = 0.05, seven studies), and walking speed of 0.03 m/s (95% CI -0.01 to 0.07, P = 0.1, nine studies). Synthesis of secondary outcomes suggested there is a beneficial effect on strength, flexibility, and balance, and possibly on mood, although the size of any such effect is unknown. There was insufficient evidence of the effect on other secondary outcomes. Based on 25 studies (3721 participants), rehabilitation does not increase risk of mortality in this population (risk ratio 0.95, 95% CI 0.80 to 1.13). However, it is possible bias has resulted in overestimation of the positive effects of physical rehabilitation. Physical rehabilitation for long-term care residents may be effective, reducing disability with few adverse events, but effects appear quite small and may not be applicable to all residents. There is insufficient evidence to reach conclusions about improvement sustainability, cost-effectiveness, or which interventions are most appropriate. Future large-scale trials are justified. | Physical rehabilitation (interventions based on exercising the body) may have a role, and this review examines the evidence available. This review included 67 trials, 36 of which were conducted in North America, 20 in Europe, and seven in Asia. In total, 6300 participants with an average age of 83 years were involved. Most interventions in some way addressed difficulties in activities of daily living. This review investigates the effects of physical rehabilitation on activities of daily living, strength, flexibility, balance, mood, cognition (memory and thinking), exercise tolerance, fear of falling, death, illness, and unwanted effects associated with the intervention, such as injuries. While variations between trials meant that we could not make specific recommendations, individual studies were often successful in demonstrating benefits to physical health from participating in different types of physical rehabilitation. |
Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl® cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm2 (95% CI 5.51 to 7.69; very low quality of evidence). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix; ranging between low and very low quality of evidence). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports. We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses. This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive. | In this Cochrane review we found six randomised controlled trials including 198 participants with 250 ulcers. Four of the randomised controlled trials were conducted in Jamaica and two in the USA. These trials included medications or dressings applied directly to the ulcer (topical medications) and medications given orally or intravenously (systemic medications). Given the very different modes of action of these two groups, we treated them separately throughout the review. The topical agents included Solcoseryl® cream, RGD peptide matrix dressing and topical antibiotics. Socoseryl aims to improve the use of oxygen by the skin tissue and so promote wound healing. Topical antibiotics are also used to prevent infection. The RGD peptide matrix is a gel that promotes cell growth. The systemic interventions included arginine butyrate, L-cartinine, and isoxsuprine. Aginine butyrate, given intravenously, is thought to accelerate wound healing, L-carnitine, given orally, is thought to improve tissue hypoxia, and isoxsuprine, given orally as isoxsuprine hydrochloride, is thought to widen blood vessels, so increasing blood flow to an affected wound. One medication, a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. However, this effect should be interpreted with caution given the high risk of bias due to the inadequacies associated with this trial report. The evidence for the use of interventions to treat people with sickle cell disease and chronic leg ulceration is not strong. All randomised clinical trials that we included in this review were associated with a high risk of bias. This systematic review has shown the need for well-designed, high-quality randomised trials to assess the benefits and harms of interventions to improve the healing of leg ulcers in people with sickle cell disease. |
One parallel trial conducted in Turkey was included. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The quality of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate quality evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate quality evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period. A small single trial contributed evidence of moderate quality that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed. | We found only one small trial for our review. It included 20 children with beta thalassaemia who were considerably shorter than they should be based on growth charts. Ten of the children were randomly selected to receive daily growth hormone treatment in addition to their usual (standard) treatment and the other 10 children just had their usual treatment. Investigators recorded the height of the children and did blood tests every three months. The trial was conducted over a one-year period. Height velocity is the rate at which a child grows taller and is calculated by measuring the difference in height over a period of time (usually measured as cm per year). In this review, the children who received growth hormone for one year had a higher height velocity (on average 2.28 cm per year more) compared to those who did not receive growth hormone. In other words, those given growth hormone grew modestly faster than those not on growth hormone. The height of a child may also be scored based on standard charts of the population (height standard deviation scores). Using this measurement, children treated with growth hormone had similar scores to those not on growth hormone at the end of one year. None of the 20 children suffered from any side effects. Although, while there was no clear difference between groups in the oral glucose tolerance test at one year, those children on growth hormone therapy had higher fasting blood glucose levels, but these were still within the normal range. The trial did not provide information beyond the one-year period, hence we do not know if the adult height of the children in the trial was affected by growth hormone therapy in any way. There were no trials in people with thalassaemia which examined the effects of growth hormone therapy over a longer period, at different dosages or in different age groups; neither were there any trials studying the effect of growth hormone therapy on adult height or general well-being (quality of life). Overall, we considered the quality of evidence for the outcomes described above (short-term growth and side effects) to be moderate, but we had a major concern that there was only a small number of participants. Based on moderate quality evidence from one small trial, the use of growth hormone may modestly improve some measures of growth. However, there was no information on final height or quality of life. More trials are needed before a clear conclusion can be drawn on the overall benefits and risks of using growth hormone in people with thalassaemia. |
We included 17 studies involving 8787 participants: nine in multidisciplinary mental health care, six in psychological therapy settings, and two in primary care. Pooling of outcome data to provide a summary estimate of effect across studies was possible only for those studies using the compound Outcome Questionnaire (OQ-45) or Outcome Rating System (ORS) PROMs, which were all conducted in multidisciplinary mental health care or psychological therapy settings, because both primary care studies identified used single symptom outcome measures, which were not directly comparable to the OQ-45 or ORS. Meta-analysis of 12 studies including 3696 participants using these PROMs found no evidence of a difference in outcome in terms of symptoms, between feedback and no-feedback groups (standardised mean difference (SMD) -0.07, 95% confidence interval (CI) -0.16 to 0.01; P value = 0.10). The evidence for this comparison was graded as low quality however, as all included studies were considered at high risk of bias, in most cases due to inadequate blinding of assessors and significant attrition at follow-up. Quality of life was reported in only two studies, social functioning in one, and costs in none. Information on adverse events (thoughts of self-harm or suicide) was collected in one study, but differences between arms were not reported. It was not possible to pool data on changes in drug treatment or referrals as only two studies reported these. Meta-analysis of seven studies including 2608 participants found no evidence of a difference in management of CMHDs between feedback and no-feedback groups, in terms of the number of treatment sessions received (mean difference (MD) -0.02 sessions, 95% CI -0.42 to 0.39; P value = 0.93). However, the evidence for this comparison was also graded as low quality. We found insufficient evidence to support the use of routine outcome monitoring using PROMs in the treatment of CMHDs, in terms of improving patient outcomes or in improving management. The findings are subject to considerable uncertainty however, due to the high risk of bias in the large majority of trials meeting the inclusion criteria, which means further research is very likely to have an important impact on the estimate of effect and is likely to change the estimate. More research of better quality is therefore required, particularly in primary care where most CMHDs are treated. Future research should address issues of blinding of assessors and attrition, and measure a range of relevant symptom outcomes, as well as possible harmful effects of monitoring, health-related quality of life, social functioning, and costs. Studies should include people treated with drugs as well as psychological therapies, and should follow them up for longer than six months. | Routine outcome monitoring of CMHDs using PROMs was not shown conclusively to be helpful in analyses combining study results, either in terms of improving patient symptom outcomes (across 12 studies), or in changing the duration of treatment for their conditions (across seven studies). It was not possible to analyse changes in drug treatment or referrals for further treatment as only two studies reported these. Similarly, health-related quality of life, social functioning, adverse events, and costs were reported in very few studies. More research of better quality is required, especially in primary care where most CMHDs are treated. Studies should include people treated with drugs as well as psychological therapies, and should follow them for longer than six months. As well as symptoms and length of treatment, studies should measure possible harms, quality of life, social functioning, and the costs of monitoring. |
Three studies (146 participants) met our selection criteria. Two studies compared multidisciplinary, fast-track palliative care versus multidisciplinary standard care while on a waiting-list control, and one study compared a multidisciplinary palliative approach versus multidisciplinary standard care at different time points (12, 16, and 24 weeks). Two were RCTs with parallel design (total 94 participants) and one was a cross-over design (52 participants). The three studies assessed palliative care as a home-based intervention. One of the three studies included participants with 'neurodegenerative diseases', with MS people being a subset of the randomised population. We assessed the risk of bias of included studies using Cochrane's 'Risk of Bias' tool. We found no evidence of differences between intervention and control groups in long-time follow-up (> six months post-intervention) for the following outcomes: mean change in health-related quality of life (SEIQoL - higher scores mean better quality of life; MD 4.80, 95% CI -12.32 to 21.92; participants = 62; studies = 1; very low-certainty evidence), serious adverse events (RR 0.97, 95% CI 0.44 to 2.12; participants = 76; studies = 1, 22 events, low-certainty evidence) and hospital admission (RR 0.78, 95% CI 0.24 to 2.52; participants = 76; studies = 1, 10 events, low-certainty evidence). The three included studies did not assess the following outcomes at long term follow-up (> six months post intervention): fatigue, anxiety, depression, disability, cognitive function, relapse-free survival, and sustained progression-free survival. We did not find any trial that compared different types of palliative care with each other. Based on the findings of the RCTs included in this review, we are uncertain whether palliative care interventions are beneficial for people with MS. There is low- or very low-certainty evidence regarding the difference between palliative care interventions versus usual care for long-term health-related quality of life, adverse events, and hospital admission in patients with MS. For intermediate-term follow-up, we are also uncertain about the effects of palliative care for the outcomes: health-related quality of life (measured by different assessments: SEIQoL or MSIS), disability, anxiety, and depression. | Three studies involving 146 participants were included in this review. All three studies compared palliative care delivered in home visits versus usual care for people with MS. Two studies included only participants with MS. The third study (Ne-PAL) included participants with MS and other neurodegenerative diseases. In all three studies, interventions focused on assessment and management of symptoms and end-of-life planning. We did not find studies that compared different types of palliative care with each other. We are uncertain about differences between palliative care versus usual care for the following outcomes assessed at long-term follow-up (> six months post-intervention): change in health-related quality of life, adverse events and hospital admission. The included studies did not assess fatigue, cognitive function, relapse-free survival or sustained progression-free survival. We are uncertain whether palliative care interventions are beneficial for people with MS. There is low- or very low-certainty evidence regarding the difference between palliative care interventions versus usual care for long-term health-related quality of life, adverse events and hospital admission. This evidence is up-to-date as of 31 October 2018. |
We identified a total of 9188 citations and included 15 RCTs conducted on 2242 participants in this review. All trials used the LMA Classic in American Society of Anesthesiologists (ASA) physical status I or II for patients undergoing elective general anaesthesia. Children were enrolled in 11 trials and adults in five trials. None of the trials were of high methodological quality. Eight of the 15 studies had adequate generation of random sequence, whereas only one trial had adequate concealment of random sequence. Three trials had blinded the outcome assessor. Thus, the majority of the studies appeared to have a high risk of bias in the study design. Using the GRADE approach, we found low quality evidence that the risk of laryngospasm was similar with early removal of the LMA (3.3%) versus late removal (2.7%): risk ratio (RR) 1.23, 95% confidence interval (CI) 0.74 to 2.03; 11 trials, 1615 participants. The quality of evidence was very low that the risk of coughing was less after early removal (13.9%) than late removal (19.4%): RR 0.52, 95% CI 0.29 to 0.94; 11 trials, 1430 participants. The quality of evidence for the risk of desaturation was also very low; there was no difference between early removal (7.9%) and late removal (10.1%): RR 0.68, 95% CI 0.4 to 1.16; 13 trials, 2037 participants. We found low quality evidence that the risk of airway obstruction was higher with early removal (15.6%) compared to late removal of the LMA (4.6%): RR 2.69, 95% CI 1.32 to 5.5; eight trials, 1313 participants. This systematic review suggests that current best evidence comparing early versus late removal of the LMA in participants undergoing general anaesthesia does not demonstrate superiority of either intervention. However, the quality of evidence available is either low or very low. There is a paucity of well designed RCTs and a need for large scale RCTs to demonstrate whether early removal or late removal of the LMA is better after general anaesthesia. | The evidence is current to August 2014. We found 15 randomized controlled trials on 2242 participants addressing this question. All the trials were performed in individuals who were not seriously ill under elective general anaesthesia. A LMA Classic was used for all studies. Children were enrolled in 11 studies and adults in five studies. None of the trials were of high methodological quality. The risks of complications such as laryngospasm (tight closure of the windpipe preventing effective breathing), and lowering of oxygen content in the blood (desaturation), were similar with early removal and late removal of the LMA. Coughing was less frequent after early removal of the LMA, with a risk of 13.9% as compared to the risk of 19.4% after late removal of the LMA. However, airway obstruction was more likely after early removal, with a risk of 15.6%, as compared to a risk of 4.6% after late removal of the LMA. No data were available on length of stay in the recovery room or hospital, or patient satisfaction. Thus, overall, this systematic review suggests that with the current available evidence, early and late removal of the LMA are comparable in persons undergoing general anaesthesia, and neither is superior in terms of safety. The quality of the evidence that is available is either low or very low for all the outcomes described. This was mainly due to poorly conducted studies, the small number of people that they recruited, and to a lesser extent, some variation in the study results. |
Five RCTs involving 309 people are included in this review. Overall, the results were inconclusive. There was no statistically significant superior effect of any locomotor training approach on walking function after SCI compared with any other kind of physical rehabilitation. The use of bodyweight supported treadmill training as locomotor training for people after SCI did not significantly increase walking velocity (0.03 m/sec with a 95% confidence interval (CI) -0.05 to 0.11; P = 0.52; I2 = 22%) nor did it increase walking capacity (-1.3 metres (95% CI -41 to 40); P = 0.95; I2 = 62%). However, in one study involving 74 people the group receiving robotic-assisted locomotor training had reduced walking capacity compared with people receiving any other intervention, a finding which needs further investigation. In all five studies there were no differences in adverse events or drop-outs between study groups. There is insufficient evidence from RCTs to conclude that any one locomotor training strategy improves walking function more than another for people with SCI. The effects especially of robotic-assisted locomotor training are not clear, therefore research in the form of large RCTs, particularly for robotic training, is needed. Specific questions about which type of locomotor training might be most effective in improving walking function for people with SCI need to be explored. | Five randomised controlled trials were identified involving 309 people with spinal cord injury. None of the locomotor interventions had a beneficial or harmful effect on the people taking part. In all five studies there were no differences in adverse events or drop-outs between study groups. There is not enough evidence to conclude which locomotor training strategy is most effective in improving walking ability in people with spinal cord injury, or that locomotor training benefits a person's ability to walk over other kinds of rehabilitation. |
One randomised clinical trial fulfilled the inclusion criteria of the review. Forty participants with multiple liver metastases of colorectal cancer and no evidence of extrahepatic disease were randomly assigned. Thirty of these participants (14 females and 16 males) were included in the analysis: 14 participants received microwave coagulation and 16 underwent conventional surgery (hepatectomy or liver resection). The diagnosis of colorectal cancer (Stage IB to IIIC; tumour (T)2 node (N)0 to T3N2) and liver metastases was confirmed by histological assessment. Mean participant age was 61 years. The tumours were resectable. The risk of bias in the trial was judged to be high. Participants were followed for three years. Mortality at the last follow-up was 64% (9/14) in the microwave group and 75% (12/16) in the conventional surgery group (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.53 to 1.39), that is, no significant difference was observed. In the microwave coagulation group, 71%, 57%, and 14% survived 1, 2, and 3 years, and in the conventional surgery group, the percentages were 69%, 56%, and 23%. The hazard ratio calculated using the Parmar method was 0.91 (0.39 to 2.15). Mean survival time was 27 months in the microwave group and 25 months in the conventional surgery group, and the mean disease-free interval was 11.3 months in the microwave group and 13.3 months in the hepatectomy group. Differences for both outcomes were not statistically significant. Reported frequency of adverse events was similar between the microwave coagulation and conventional surgery groups, except for the required blood transfusion, which was more common in the conventional surgery group. No intervention-related mortality was observed. After treatment, the carcinoembryonic antigen level decreased significantly in both groups. On the basis of one randomised clinical trial, which did not describe allocation concealment or blinding, and which excluded from analysis 25% of participants after random assignment, evidence is insufficient to show whether microwave coagulation brings any significant benefit in terms of survival or recurrence compared with conventional surgery for participants with liver metastases from colorectal cancer. The number of adverse events, except for the requirement for blood transfusion, which was more common in the liver resection group, was similar in both groups. At present, microwave therapy cannot be recommended outside randomised clinical trials. | One randomised clinical trial comparing microwave coagulation with conventional surgery (liver resection) is included in the review: 14 participants received microwave coagulation and 16 participants underwent conventional surgery. The trial was judged to have a high risk of systematic error (ie, overestimation of benefits and underestimation of harms). On the basis of one randomised trial, which did not describe allocation concealment or blinding, and which excluded from analysis 25% of participants after random assignment, evidence is insufficient to show whether microwave coagulation provides any significant benefit in terms of survival or recurrence compared with conventional surgery for participants with liver metastases from colorectal cancer. The number of adverse events, except for the requirement for blood transfusion, which was more common in the liver resection group, was similar in both groups. At present, microwave therapy cannot be recommended outside randomised clinical trials. |
We included 63 trials randomising a total of 85,550 participants (mean age 57.4 years). Only one trial was at low risk of bias. The remaining trials were at high risk of bias. The quality of the evidence according to GRADE ranged from very low to high. Fifty-six trials commenced beta-blockers during the acute phase of acute myocardial infarction and seven trials during the subacute phase. At our primary time point 'less than three months follow-up', meta-analysis showed that beta-blockers versus placebo or no intervention probably reduce the risk of a reinfarction during follow-up (risk ratio (RR) 0.82, 98% confidence interval (CI) 0.73 to 0.91; 67,562 participants; 18 trials; moderate-quality evidence) with an absolute risk reduction of 0.5% and a number needed to treat for an additional beneficial outcome (NNTB) of 196 participants. However, we found little or no effect of beta-blockers when assessing all-cause mortality (RR 0.94, 97.5% CI 0.90 to 1.00; 80,452 participants; 46 trials/47 comparisons; high-quality evidence) with an absolute risk reduction of 0.4% and cardiovascular mortality (RR 0.99, 95% CI 0.91 to 1.08; 45,852 participants; 1 trial; moderate-quality evidence) with an absolute risk reduction of 0.4%. Regarding angina, it is uncertain whether beta-blockers have a beneficial or harmful effect (RR 0.70, 98% CI 0.25 to 1.84; 98 participants; 3 trials; very low-quality evidence) with an absolute risk reduction of 7.1%. None of the trials specifically assessed nor reported serious adverse events according to ICH-GCP. Only two trials specifically assessed major adverse cardiovascular events, however, no major adverse cardiovascular events occurred in either trial. At maximum follow-up beyond three months, meta-analyses showed that beta-blockers versus placebo or no intervention probably reduce the risk of all-cause mortality (RR 0.93, 97.5% CI 0.86 to 0.99; 25,210 participants; 21 trials/22 comparisons; moderate-quality evidence) with an absolute risk reduction of 1.1% and a NNTB of 91 participants, and cardiovascular mortality (RR 0.90, 98% CI 0.83 to 0.98; 22,457 participants; 14 trials/15 comparisons; moderate-quality evidence) with an absolute risk reduction of 1.2% and a NNTB of 83 participants. However, it is uncertain whether beta-blockers have a beneficial or harmful effect when assessing major adverse cardiovascular events (RR 0.81, 97.5% CI 0.40 to 1.66; 475 participants; 4 trials; very low-quality evidence) with an absolute risk reduction of 1.7%; reinfarction (RR 0.89, 98% CI 0.75 to 1.08; 6825 participants; 14 trials; low-quality evidence) with an absolute risk reduction of 0.9%; and angina (RR 0.64, 98% CI 0.18 to 2.0; 844 participants; 2 trials; very low-quality evidence). None of the trials specifically assessed nor reported serious adverse events according to ICH-GCP. None of the trials assessed quality of life. We identified two ongoing randomised clinical trials investigating the effect of early administration of beta-blockers after percutaneous coronary intervention or thrombolysis to patients with an acute myocardial infarction and one ongoing trial investigating the effect of long-term beta-blocker therapy. Our present review indicates that beta-blockers for suspected or diagnosed acute myocardial infarction probably reduce the short-term risk of a reinfarction and the long-term risk of all-cause mortality and cardiovascular mortality. Nevertheless, it is most likely that beta-blockers have little or no effect on the short-term risk of all-cause mortality and cardiovascular mortality. Regarding all remaining outcomes (serious adverse events according to ICH-GCP, major adverse cardiovascular events (composite of cardiovascular mortality and non-fatal myocardial infarction during follow-up), the long-term risk of a reinfarction during follow-up, quality of life, and angina), further information is needed to confirm or reject the clinical effects of beta-blockers on these outcomes for people with or suspected of acute myocardial infarction. | We found 63 randomised clinical trials where people with or suspected of a heart attack were randomly allocated to receiving beta-blockers compared with placebo or no intervention. The 63 trials included 85,550 adults with a mean age of 57.4 years. Only one trial was at low risk of bias. The remaining trials were at high risk of bias. The quality of the evidence according to GRADE ranged from very low to high. Fifty-six trials commenced beta-blockers versus control during the acute phase of acute myocardial infarction and seven trials during the subacute phase. We found 33 trials that were fully or partly funded by the industry, 20 trials that did not report their funding source, and 10 trials that were funded by other sources than the industry. Our present review shows that people receiving beta-blockers compared with people receiving placebo or no intervention seem at lower risk of a new heart attack in the acute phase after a heart attack. People receiving beta-blockers also seem at lower risk of dying from any cause and from any cardiac cause at long-term follow-up after a heart attack. Nevertheless, people receiving beta-blockers do not seem to have a lower or a higher risk of dying from any cause or from any cardiac cause in the acute phase after a heart attack. The effects of beta-blockers on all remaining outcomes (serious adverse events according to International Conference on Harmonization - Good Clinical Practice, major adverse cardiovascular events (composite of dying from a cardiac cause and a new non-fatal heart attack), new heart attack at long-term follow-up, quality of life, and angina) are uncertain due to none or sparse data. |
We included seven trials of antifungal agents in children with prolonged fever and neutropenia (suspected fungal infection) and candidaemia or invasive candidiasis (proven fungal infection). Four trials compared a lipid preparation of amphotericin B with conventional amphotericin B (395 participants), one trial compared an echinocandin with a lipid preparation of amphotericin B (82 participants) in suspected infection; one trial compared an echinocandin with a lipid preparation of amphotericin B in children with candidaemia or invasive candidiasis (109 participants) and one trial compared different azole antifungals in children with candidaemia (43 participants). No difference in all-cause mortality and other primary endpoints (mortality related to fungal infection or complete resolution of fungal infections) were observed. No difference in breakthrough fungal infection was observed in children with prolonged fever and neutropenia. When lipid preparations and conventional amphotericin B were compared in children with prolonged fever and neutropenia, nephrotoxicity was less frequently observed with a lipid preparation (RR 0.43, 95% CI 0.21 to 0.90, P = 0.02) however substantial heterogeneity was observed (I2 = 59%, P = 0.06). Children receiving liposomal amphotericin B were less likely to develop infusion-related reactions compared with conventional amphotericin B (chills: RR 0.37, 95% CI 0.21 to 0.64, P = 0.0005). Children receiving a colloidal dispersion were more likely to develop such reactions than with liposomal amphotericin B (chills: RR 1.76, 95% CI 1.09 to 2.85, P = 0.02). The rate of other clinically significant adverse reactions attributed to the antifungal agent (total reactions; total reactions leading to treatment discontinuation, dose reduction or change in therapy; hypokalaemia and hepatotoxicity) were not significantly different. When echinocandins and lipid preparations were compared, the rate of clinically significant adverse reactions (total reactions; total reactions leading to treatment discontinuation, dose reduction or change in therapy) were not significantly different. Limited paediatric data are available comparing antifungal agents in children with proven, probable or suspected invasive fungal infection. No differences in mortality or treatment efficacy were observed when antifungal agents were compared. Children are less likely to develop nephrotoxicity with a lipid preparation of amphotericin B compared with conventional amphotericin B. Further comparative paediatric antifungal drug trials and epidemiological and pharmacological studies are required highlighting the differences between neonates, children and adults with invasive fungal infections. | Pooling the data from the few studies that were available suggest kidney damage was less likely with a lipid preparation of amphotericin B compared with conventional amphotericin B. It is reasonable to recommend a lipid preparation of amphotericin B, if cost permits. No significant differences have been observed in children when other antifungal agents have been compared. More studies in children evaluating available antifungal are required to further clarify any benefits with regard to the risk of dying, prospects of complete recovery and drug toxicities. |
We included 49 studies involving 4807 women: 13 studies evaluated pelvic endometriosis, 10 endometriomas and 15 DIE, and 33 studies addressed endometriosis at specific anatomical sites. Most studies were of poor methodological quality. The most studied modalities were transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI), with outcome measures commonly demonstrating diversity in diagnostic estimates; however, sources of heterogeneity could not be reliably determined. No imaging test met the criteria for a replacement or triage test for detecting pelvic endometriosis, albeit TVUS approached the criteria for a SpPin triage test. For endometrioma, TVUS (eight studies, 765 participants; sensitivity 0.93 (95% confidence interval (CI) 0.87, 0.99), specificity 0.96 (95% CI 0.92, 0.99)) qualified as a SpPin triage test and approached the criteria for a replacement and SnNout triage test, whereas MRI (three studies, 179 participants; sensitivity 0.95 (95% CI 0.90, 1.00), specificity 0.91 (95% CI 0.86, 0.97)) met the criteria for a replacement and SnNout triage test and approached the criteria for a SpPin test. For DIE, TVUS (nine studies, 12 data sets, 934 participants; sensitivity 0.79 (95% CI 0.69, 0.89) and specificity 0.94 (95% CI 0.88, 1.00)) approached the criteria for a SpPin triage test, and MRI (six studies, seven data sets, 266 participants; sensitivity 0.94 (95% CI 0.90, 0.97), specificity 0.77 (95% CI 0.44, 1.00)) approached the criteria for a replacement and SnNout triage test. Other imaging tests assessed in small individual studies could not be statistically evaluated. TVUS met the criteria for a SpPin triage test in mapping DIE to uterosacral ligaments, rectovaginal septum, vaginal wall, pouch of Douglas (POD) and rectosigmoid. MRI met the criteria for a SpPin triage test for POD and vaginal and rectosigmoid endometriosis. Transrectal ultrasonography (TRUS) might qualify as a SpPin triage test for rectosigmoid involvement but could not be adequately assessed for other anatomical sites because heterogeneous data were scant. Multi-detector computerised tomography enema (MDCT-e) displayed the highest diagnostic performance for rectosigmoid and other bowel endometriosis and met the criteria for both SpPin and SnNout triage tests, but studies were too few to provide meaningful results. Diagnostic accuracies were higher for TVUS with bowel preparation (TVUS-BP) and rectal water contrast (RWC-TVS) and for 3.0TMRI than for conventional methods, although the paucity of studies precluded statistical evaluation. None of the evaluated imaging modalities were able to detect overall pelvic endometriosis with enough accuracy that they would be suggested to replace surgery. Specifically for endometrioma, TVUS qualified as a SpPin triage test. MRI displayed sufficient accuracy to suggest utility as a replacement test, but the data were too scant to permit meaningful conclusions. TVUS could be used clinically to identify additional anatomical sites of DIE compared with MRI, thus facilitating preoperative planning. Rectosigmoid endometriosis was the only site that could be accurately mapped by using TVUS, TRUS, MRI or MDCT-e. Studies evaluating recent advances in imaging modalities such as TVUS-BP, RWC-TVS, 3.0TMRI and MDCT-e were observed to have high diagnostic accuracies but were too few to allow prudent evaluation of their diagnostic role. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Future well-designed diagnostic studies undertaken to compare imaging tests for diagnostic test accuracy and costs are recommended. | Evidence included in this review is current to April 2015. We included 49 studies involving 4807 participants. Thirteen studies evaluated pelvic endometriosis, 10 studies ovarian endometrioma, 15 studies deep endometriosis (endometriosis deeply situated in tissues in the pelvis) and 33 studies endometriosis at specific sites within the pelvic cavity. All studies included women of reproductive age who were undergoing diagnostic surgery because they had symptoms of endometriosis. None of the imaging methods was accurate enough to provide this information on overall pelvic endometriosis. Transvaginal ultrasound identified ovarian endometriosis with enough accuracy to help surgeons determine whether surgery was needed, and magnetic resonance imaging (MRI) was sufficiently accurate to replace surgery in diagnosing endometrioma but was evaluated in only a small number of studies. Other imaging tests were assessed in small individual studies and could not be evaluated in a meaningful way. Transvaginal ultrasound could be used to locate more anatomical sites of deep endometriosis when compared with MRI, helping surgeons better plan an operative procedure. Endometriosis in the lower bowel appears to be relatively accurately identified by both transvaginal and transrectal ultrasound, by MRI and by multi-detector computerised tomography enema. New types of ultrasound and MRI show a lot of promise in detecting endometriosis but studies are too few to clearly show their diagnostic value. Generally the studies were of low methodological quality, and most imaging techniques were assessed by only a small number of studies. Differences between studies involved how they were run, groups of women studied, ways imaging tests were performed and how surgery was undertaken. Additional high-quality research is needed to accurately evaluate the diagnostic potential of non-invasive imaging tests for endometriosis. |
Eight trials with a total of 348 participants were included. Comparing EN to TPN for acute pancreatitis, the relative risk (RR) for death was 0.50 (95% CI 0.28 to 0.91), for multiple organ failure (MOF) was 0.55 (95% CI 0.37 to 0.81), for systemic infection was 0.39 (95% CI 0.23 to 0.65), for operative interventions was 0.44 (95% CI 0.29 to 0.67), for local septic complications was 0.74 (95% CI 0.40 to 1.35), and for other local complications was 0.70 (95% CI 0.43 to 1.13). Mean length of hospital stay was reduced by 2.37 days in EN vs TPN groups (95% CI -7.18 to 2.44). Furthermore, a subgroup analysis for EN vs TPN in patients with severe acute pancreatitis showed a RR for death of 0.18 (95% CI 0.06 to 0.58) and a RR for MOF of 0.46 (95% CI 0.16 to 1.29). In patients with acute pancreatitis, enteral nutrition significantly reduced mortality, multiple organ failure, systemic infections, and the need for operative interventions compared to those who received TPN. In addition, there was a trend towards a reduction in length of hospital stay. These data suggest that EN should be considered the standard of care for patients with acute pancreatitis requiring nutritional support. | This review found that patients with acute pancreatitis receiving enteral nutrition have fewer episodes of death, systemic infections, multiple organ failure and operative interventions. This data suggests that EN should be considered the standard of care for patients with acute pancreatitis requiring nutritional support. |
We included 13 RCTs (701 people). Six of the RCTs included only children aged 1 to 18 years and seven involved only adults (from 18 to 65 years of age). The mean TBSA of the included participants was greater than 49%. Twelve studies compared rhGH with placebo and one study compared rhGH with oxandrolone. Two trials found that compared with placebo, burn wounds in adults treated with rhGH healed more quickly (by 9.07 days; 95% confidence interval (CI) 4.39 to 13.76, I² = 0%). The donor site healing time was significantly shorter in rhGH-treated adults compared with placebo-treated participants (by 3.15 days; 95% CI 1.54 to 4.75, I² = 0%). Two studies in children with the outcome of donor site healing time could be pooled and the donor site healing time was shorter in the rhGH-treated children (by 1.70 days; 95% CI 0.87 to 2.53, I² = 0%). No studies reporting the outcome of wound infection were found. The incidence of hyperglycaemia was higher in adults during rhGH treatment compared with placebo (risk ratio (RR) 2.43; 95% CI 1.54 to 3.85), but not in children. Pooling the studies of adults and children yielded a significantly higher incidence of hyperglycaemia in the rhGH-treated participants (RR 2.65; 95% CI 1.68 to 4.16). There is some evidence that using rhGH in people with large burns (more than 40% of the total body surface area) could result in more rapid healing of the burn wound and donor sites in adults and children, and in reduced length of hospital stay, without increased mortality or scarring, but with an increased risk of hyperglycaemia. This evidence is based on studies with small sample sizes and risk of bias and requires confirmation in higher quality, adequately powered trials. | We found 13 eligible randomised controlled trials (RCTs) involving 701 people for inclusion in this review. There is some evidence that recombinant growth hormone therapy in people with burns covering more than 40% of the total body surface area helps burn wounds and donor sites heal more rapidly and reduce the length of hospital stay, without increased mortality or increased scarring. We found it difficult to assess the quality of these studies due to poor reporting therefore we cannot be completely confident in their results. |
A total of 1092 participants randomly assigned to the low pressure group (509 participants) and the standard pressure group (583 participants) in 21 trials provided information for this review on one or more outcomes. Three additional trials comparing low pressure pneumoperitoneum with standard pressure pneumoperitoneum (including 179 participants) provided no information for this review. Most of the trials included low anaesthetic risk participants undergoing elective laparoscopic cholecystectomy. One trial including 140 participants was at low risk of bias. The remaining 20 trials were at high risk of bias. The overall quality of evidence was low or very low. No mortality was reported in either the low pressure group (0/199; 0%) or the standard pressure group (0/235; 0%) in eight trials that reported mortality. One participant experienced the outcome of serious adverse events (low pressure group 1/179, 0.6%; standard pressure group 0/215, 0%; seven trials; 394 participants; RR 3.00; 95% CI 0.14 to 65.90; very low quality evidence). Quality of life, return to normal activity, and return to work were not reported in any of the trials. The difference between groups in the conversion to open cholecystectomy was imprecise (low pressure group 2/269, adjusted proportion 0.8%; standard pressure group 2/287, 0.7%; 10 trials; 556 participants; RR 1.18; 95% CI 0.29 to 4.72; very low quality evidence) and was compatible with an increase, a decrease, or no difference in the proportion of conversion to open cholecystectomy due to low pressure pneumoperitoneum. No difference in the length of hospital stay was reported between the groups (five trials; 415 participants; MD -0.30 days; 95% CI -0.63 to 0.02; low quality evidence). Operating time was about two minutes longer in the low pressure group than in the standard pressure group (19 trials; 990 participants; MD 1.51 minutes; 95% CI 0.07 to 2.94; very low quality evidence). Laparoscopic cholecystectomy can be completed successfully using low pressure in approximately 90% of people undergoing laparoscopic cholecystectomy. However, no evidence is currently available to support the use of low pressure pneumoperitoneum in low anaesthetic risk patients undergoing elective laparoscopic cholecystectomy. The safety of low pressure pneumoperitoneum has to be established. Further well-designed trials are necessary, particularly in people with cardiopulmonary disorders who undergo laparoscopic cholecystectomy. | A total of 1092 patients were studied in 21 trials. Patients were assigned to a low pressure group (509 patients) or a standard pressure group (583 patients). The choice of treatment was determined by a method similar to the toss of a coin. Most of the trials included low surgical risk patients undergoing planned laparoscopic cholecystectomy. Laparoscopic cholecystectomy could be completed successfully using low pressure in approximately 90% of people undergoing this procedure. No deaths were reported in either low pressure or standard pressure groups in eight trials that reported deaths (total of 434 patients in both groups). Seven trials with 394 patients described complications related to surgery. One participant experienced the outcome of serious adverse events (low pressure group 1/179, 0.6%; standard pressure group 0/215, 0%). Quality of life, return to normal activity, and return to work were not reported in any of the trials. The difference in the percentage of people undergoing conversion to open operation (from key-hole operation) between the low pressure group (2/269; 0.8%) and the standard pressure group (2/287; 0.7%) was imprecise. This was reported in 10 studies. No difference was noted in the length of hospital stay between the groups. Operating time was about two minutes longer (very low quality evidence) in the low pressure group than in the standard pressure group. Currently no evidence is available to support the use of low pressure pneumoperitoneum in low surgical risk patients undergoing planned laparoscopic cholecystectomy. The safety of low pressure pneumoperitoneum has to be established. Only one trial including 140 participants was at low risk of bias (low chance of arriving at wrong conclusions because of study design). The remaining 20 trials were at high risk of bias (high chance of arriving at wrong conclusions because of trial design). The overall quality of evidence was very low. Further well-designed trials are necessary, particularly in high surgical risk patients undergoing laparoscopic cholecystectomy. |
Six trials met all our eligibility criteria and provided extractable data. Three trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Five trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (6 trials, 6497 participants, risk ratio (RR) of developing subsequent gastric cancer 0.66; 95% confidence interval (CI) 0.46 to 0.95; moderate-quality evidence). Only one trial reported effect of eradication of H. pylori on development of subsequent oesophageal cancer (2 (0.2%) among 817 participants assigned to eradication therapy, compared with 1 (0.1%) of 813 participants allocated to placebo; RR 1.99; 95% CI 0.18 to 21.91). The effect of H. pylori eradication on preventing death from gastric cancer compared with placebo or no treatment was uncertain due to wide confidence intervals (3 trials, 4475 participants, RR 0.67; 95% CI 0.40 to 1.11; moderate-quality evidence). There was no evidence of an effect on all-cause mortality (4 trials, 5253 participants, RR 1.09; 95% CI 0.86 to 1.38; moderate-quality evidence). Adverse events data were poorly reported. We found limited, moderate-quality evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations. | A literature search up to December 2013 found 6 trials (containing 6497 participants, 3 trials at low risk of bias). Five of the studies were based in Asia. We found that antibiotics for H. pylori have a small benefit in preventing gastric cancer (51 (1.6%) of 3294 participants given treatment developed gastric cancer subsequently, compared with 76 (2.4%) of 3203 given no treatment or a placebo), but it is unclear whether or not they decrease the number of deaths from the disease, increase or decrease the number of deaths due to any cause, or increase or decrease the number of cases of oesophageal cancer. Data about side effects of treatment were poorly reported. Three trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. One study was at high risk of bias because no placebo was used for the active eradication therapy regimen, and so this part of the trial was unblinded, and the other study was at high risk of bias due to inconsistencies in data reporting at the two points of follow-up. We were unable to resolve this discrepancy despite contacting the original authors. As a result, we downgraded the quality of evidence from high to moderate due to serious risk of bias. |
We included 26 trials, which randomised 4979 participants, in this review. Meta-analysis of 10 trials clearly demonstrated reduction of onset of VF defects in treated OHT (OR 0.62, 95% CI 0.47 to 0.81). No single drug showed a significant VF protection compared to placebo or untreated controls. We did identify some border line evidence for a positive influence of treatment on VF prognosis (OR 0.67, 95% CI 0.45 to 1.00) for the beta-blockers . The results of this review support the current practice of IOP lowering treatment of OHT. A visual field protective effect has been clearly demonstrated for medical IOP lowering treatment. Positive but weak evidence for a beneficial effect of the class of beta-blockers has been shown. Direct comparisons of prostaglandins or brimonidine to placebo are not available and the comparison of dorzolamide to placebo failed to demonstrate a protective effect. However, absence of data or failure to prove effectiveness should not be interpreted as proof of absence of any effect. The decision to treat a patient or not, as well as the decision regarding the drug with which to start treatment, should remain individualised, taking in to account the amount of damage, the level of IOP, age and other patient characteristics. | The results of this review support the current practice of topical medication to lower IOP and clearly demonstrate a visual field protective effect. The review authors identified a total of 26 controlled trials that randomised 4979 people with OHT or open angle glaucoma to receive topical medication or a placebo, another topical medication or no treatment for at least a year. Meta-analysis of 10 trials testing different topical medications against placebo or untreated controls showed reduced incidence of glaucomatous visual field defects with treatment for people with OHT. The odds ratio (OR) was 0.62 (range 0.5 to 0.8). The class of beta-blockers (including timolol) had positive but weak evidence for a beneficial effect in protecting against visual field defects (OR 0.7, range 0.5 to 1.0). No single drug showed significant visual field protection in OHT with the evidence available. Medications included beta-blockers, dorzolamide, brimonidine, pilocarpine and epinephrine. From the reports, the majority of trials were of low methodological quality. Local and systemic side effects leading to treatment being stopped were often poorly reported and did not appear to differ between treatment groups. Drop-outs due to side effects occurred with similar frequency in people treated with beta-blocker or placebo and appeared to be less with timolol compared to brimonidine, in three trials. |
We identified no new trials for the 2016 update. This review includes two trials, but we included only one trial, with 24 women, in the analyses. The overall risk of bias was unclear owing to lack of methodological detail. Using the GRADE method, we judged the quality of the evidence to be very low. We downgraded evidence for risk of bias and for imprecision (wide confidence intervals and evidence based on a single small trial). Comparison of NSAIDs (naproxen) versus placebo revealed no evidence of a positive effect on pain relief (odds ratio (OR) 3.27, 95% confidence interval (CI) 0.61 to 17.69; one trial, 24 women; very low-quality evidence) in women with endometriosis. Evidence indicating whether women taking NSAIDs (naproxen) were less likely to require additional analgesia (OR 0.12, 95% CI 0.01 to 1.29; one trial, 24 women; very low-quality evidence) or to experience side effects (OR 0.46, 95% CI 0.09 to 2.47; one trial, 24 women; very low-quality evidence) when compared with placebo was inconclusive. Studies provided no data on quality of life, effects on daily activities, absence from work or school, need for more invasive treatment or participant satisfaction with treatment. Owing to lack of high-quality evidence and lack of reporting of outcomes of interest for this review, we can make no judgement as to whether NSAIDs (naproxen) are effective in managing pain caused by endometriosis. There is no evidence that one NSAID is more effective than another. As shown in other Cochrane reviews, women taking NSAIDs must be aware that these drugs may cause unintended effects. | We searched for new evidence in October 2016 and identified no new randomised controlled trials. From previous updates, this review found limited evidence on the effectiveness of NSAIDs (specifically naproxen) for management of pain caused by endometriosis. This review is also limited in that it includes only one study with data suitable for analysis, and this study involved only 20 women. Available evidence is of very low quality, mainly owing to poor reporting of methods, lack of precision in findings for overall pain relief, unintended side effects of treatment and the need for extra pain relief. The included trial did not report on quality of life, effects on daily activities, absence from work or school or participant satisfaction with treatment. Available evidence does not allow us to conclude whether NSAIDs are effective for managing pain caused by endometriosis, or whether any individual NSAID is more effective than another. As has been shown in other Cochrane reviews, women who use NSAIDs must be aware that NSAIDs may cause adverse effects such as nausea, vomiting, headache and drowsiness. Unless we identify new evidence in the future, we will not update this review again. Evidence was of very low quality owing to risk of bias and imprecision (findings were based on a single small trial). |
The original review included eight studies on migraine. Overall, we now include 11 studies on five SSRIs and one SNRI with a total of 585 participants. Six studies were placebo-controlled, four compared a SSRI or SNRI to amitriptyline, and one was a head-to-head comparison (escitalopram versus venlafaxine). Most studies had methodological or reporting shortcomings (or both): all studies were at unclear risk of selection and reporting bias. Follow-up rarely extended beyond three months. The lack of adequate power of most of the studies is also a major concern. Few studies explored the effect of SSRIs or SNRIs on migraine frequency, the primary endpoint. Two studies with unclear reporting compared SSRIs and SNRIs to placebo, suggesting a lack of evidence for a difference. Two studies compared SSRIs or SNRIs versus amitriptyline and found no evidence for a difference in terms of migraine frequency (standardised mean difference (SMD) 0.04, 95% confidence interval (CI) -0.72 to 0.80; I2 = 72%), or other secondary outcomes such as migraine intensity and duration. SSRIs or SNRIs were generally more tolerable than tricyclics. However, the two groups did not differ in terms of the number of participants who withdrew due to adverse advents or for other reasons (one study, odds ratio (OR) 0.39, 95% CI 0.10 to 1.50 and OR 0.42, 95% CI 0.13 to 1.34). We did not find studies comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. antiepileptics and anti-hypertensives). Since the last version of this review, the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine as preventive drugs for migraine. There is no evidence to consider SSRIs or venlafaxine as more effective than placebo or amitriptyline in reducing migraine frequency, intensity, and duration over two to three months of treatment. No reliable information is available at longer-term follow-up. Our conclusion is that the use of SSRIs and SNRIs for migraine prophylaxis is not supported by evidence. | This is an update of a previous review that included studies on migraine and tension-type headache. This original review has been split in two separate reviews: this update addresses only studies on migraine, while a second focuses on tension-type headache. In November 2014, we identified three new studies. Eight studies were already included in the previous version of the review. Overall, we analysed a total of 585 participants. All the studies had a small number of participants and were conducted over a period of two to three months. Only a few were of high quality. The results suggest that SSRIs and SNRIs are no better than placebo (sugar pill) for reducing the number of migraine attacks. There were no differences in minor side effects between participants treated with SSRIs or SNRIs versus those treated with placebo. SSRIs and SNRIs seem not to offer advantages when compared to other active treatments, specifically the tricyclic antidepressant amitriptyline. The participants treated with SSRIs or SNRIs suffered fewer minor side effects than those who took amitriptyline, however the number of people who stopped taking one drug or the other due to side effects was approximately equal. These results are based on short-term trials (no more than three months), which are not properly sized and feature serious methodological deficiencies. We did not find studies comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. antiepileptics and anti-hypertensives). |
A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three studies versus escitalopram and two versus fluoxetine), four studies (overall 1978 participants) comparing duloxetine with a newer antidepressants (three with venlafaxine and one with desvenlafaxine, respectively) and one study (overall 453 participants) comparing duloxetine with an antipsychotic drug which is also used as an antidepressive agent, quetiapine. No studies were found comparing duloxetine with tricyclic antidepressants. The pooled confidence intervals were rather wide and there were no statistically significant differences in efficacy when comparing duloxetine with other antidepressants. However, when compared with escitalopram or venlafaxine, there was a higher rate of drop out due to any cause in the patients randomised to duloxetine (odds ratio (OR) 1.62; 95% confidence interval (CI) 1.01 to 2.62 and OR 1.56; 95% CI 1.14 to 2.15, respectively). There was also some weak evidence suggesting that patients taking duloxetine experienced more adverse events than paroxetine (OR 1.24; 95% CI 0.99 to 1.55). Duloxetine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. No differences in terms of efficacy were found, even though duloxetine was worse than some SSRIs (most of all, escitalopram) and newer antidepressants (like venlafaxine) in terms of acceptability and tolerability. Unfortunately, we only found evidence comparing duloxetine with a handful of other active antidepressive agents and only a few trials per comparison were found (in some cases we retrieved just one trial). This limited the power of the review to detect moderate, but clinically meaningful differences between the drugs. As many statistical tests have been used in the review, the findings from this review are better thought of as hypothesis forming rather than hypothesis testing and it would be very comforting to see the conclusions replicated in future trials. Most of included studies were sponsored by the drug industry manufacturing duloxetine. As for all other new investigational compounds, the potential for overestimation of treatment effect due to sponsorship bias should be borne in mind. In the present review no trials reported economic outcomes. Given that several SSRIs and the great majority of antidepressants are now available as generic formulation (only escitalopram, desvenlafaxine and duloxetine are still on patent), more comprehensive economic estimates of antidepressant treatment effect should be considered to better inform healthcare policy. | In the present review we assessed the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressants in the acute-phase treatment of major depression. Sixteen randomised controlled trials (5735 participants) were included. Duloxetine was not more effective than some other new antidepressant agents in the acute-phase treatment of major depression, and it was less well tolerated than escitalopram and venlafaxine as more patients allocated to duloxetine withdrew treatment before study end. However, due to the limited number of studies per comparison these results should be interpreted with caution. |
Twenty-seven studies (29 experimental groups) met the review entry criteria, randomising a total of 1925 participants. The studies identified assessed the effects of 21 different herbal preparations. Study quality varied considerably, and the sample sizes were often small. For primary outcomes (exacerbations, steroids use and lung function measurements): Two out of six studies reporting change in FEV1 were positive, with very few data available on the frequency of exacerbations. One study which did report these data was negative. Health-related quality of life was only measured in one trial. The evidence base for the effects of herbal treatments is hampered by the variety of treatments assessed, poor reporting quality of the studies and lack of available data. The data that are available from the studies provide only a small insight into the long-term efficacy and harm profiles of these treatments. The absence of common endpoint measurements limits the validity of our findings further. Positive findings in this review warrant additional well-designed trials in this area. | We reviewed evidence from 27 trials covering 21 different herbal treatments in both adults and children from both in-patient and out-patient settings. In general, the reporting of trials was poor. The outcomes measured by the trials varied considerably which made it difficult to compare the results of studies that did look at the same treatment. On the basis of the available evidence it is not possible to show whether any of these herbal treatments can improve asthma symptoms. Further trials of high quality are needed to assess the use of herbal treatments in asthma. |
We included 13 studies: one cluster randomised controlled trial (CRCT) and 12 ITS studies, involving 40 hospitals, 51 intensive care units (ICUs), 27 wards, and more than 3504 patients and 1406 healthcare professionals. Six of the included studies targeted adherence to guidelines to prevent central line-associated blood stream infections (CLABSIs); another six studies targeted adherence to guidelines to prevent ventilator-associated pneumonia (VAP), and one study focused on interventions to improve urinary catheter practices. We judged all included studies to be at moderate or high risk of bias. The largest median effect on rates of VAP was found at nine months follow-up with a decrease of 7.36 (-10.82 to 3.14) cases per 1000 ventilator days (five studies and 15 sites). The one included cluster randomised controlled trial (CRCT) observed, improved urinary catheter practices five weeks after the intervention (absolute difference 12.2 percentage points), however, the statistical significance of this is unknown given a unit of analysis error. It is worth noting that N = 6 interventions that did result in significantly decreased infection rates involved more than one active intervention, which in some cases, was repeatedly administered over time, and further, that one intervention involving specialised oral care personnel showed the largest step change (-22.9 cases per 1000 ventilator days (standard error (SE) 4.0), and also the largest slope change (-6.45 cases per 1000 ventilator days (SE 1.42, P = 0.002)) among the included studies. We attempted to combine the results for studies targeting the same indwelling medical device (central line catheters or mechanical ventilators) and reporting the same outcomes (CLABSI and VAP rate) in two separate meta-analyses, but due to very high statistical heterogeneity among included studies (I2 up to 97%), we did not retain these analyses. Six of the included studies reported post-intervention adherence scores ranging from 14% to 98%. The effect on rates of infection were mixed and the effect sizes were small, with the largest median effect for the change in level (interquartile range (IQR)) for the six CLABSI studies being observed at three months follow-up was a decrease of 0.6 (-2.74 to 0.28) cases per 1000 central line days (six studies and 36 sites). This change was not sustained over longer follow-up times. The low to very low quality of the evidence of studies included in this review provides insufficient evidence to determine with certainty which interventions are most effective in changing professional behaviour and in what contexts. However, interventions that may be worth further study are educational interventions involving more than one active element and that are repeatedly administered over time, and interventions employing specialised personnel, who are focused on an aspect of care that is supported by evidence e.g. dentists/dental auxiliaries performing oral care for VAP prevention. | We identified 13 studies: one cluster randomised controlled trial (CRCT) and 12 interrupted time series (ITS) studies, involving 40 hospitals, 51 intensive care units (ICUs), 27 wards and more than 1406 healthcare professionals and 3504 patients, which assessed the impact of different interventions to reduce the occurrence of device-related infections for inclusion in this review. We judged all studies to be at moderate to high risk of bias. The effect sizes were small with the largest median effect for studies addressing central line associated blood stream infections (CLABSIs) occurring immediately after the implementation of an intervention to improve adherence to guidelines, in the majority of studies this change was not sustained over longer follow-up times. The median effect for studies aiming to reduce ventilator-associated pneumonia (VAP) was somewhat greater and was sustained up to 12 months follow-up. The results of six studies that reported adherence/non-adherence with infection control recommendations showed very varying adherence scores ranging from 14% to 98%. The low to very low quality of the evidence of the studies included in this review provides insufficient evidence to determine with certainty which interventions are most effective in changing professional behaviour and in what contexts. However, interventions that may be worth further study are educational interventions consisting of more than one active element and that are repeatedly administered over time, and interventions employing dedicated personnel, who are focused on a certain aspect of care that is supported by evidence e.g. dentists/dental auxiliaries providing oral care. If healthcare organisations and policy makers wish to improve professional adherence to guidelines for the prevention of device-related infections, funding of well designed studies to generate high quality evidence is needed to guide policy. |
We included six randomized controlled trials (RCTs). Four studies had unclear risk of bias and two had high risk of bias. The results of these RCTs were not consistent; two demonstrated no differences between blinded and unblinded assessments, two found that blinded assessments had significantly lower quality scores, and another observed significantly higher quality scores for blinded assessments. The remaining study did not report the level of significance. We pooled five studies reporting sufficient information in a meta-analysis. We observed no statistically significant difference in risk of bias assessments between blinded or unblinded assessments (standardized mean difference -0.13, 95% confidence interval -0.42 to 0.16). The mean difference might be slightly inaccurate, as we did not adjust for clustering in our meta-analysis. We observed inconsistency of results visually and noted statistical heterogeneity. Our review highlights that discordance exists between studies examining blinded versus unblinded risk of bias assessments at the systematic review level. The best approach to risk of bias assessment remains unclear, however, given the increased time and resources required to conceal reports effectively, it may not be necessary for risk of bias assessments to be conducted under blinded conditions in a systematic review. | When researchers want to answer a question they can use an approach called a systematic review, which is intended to examine all of the studies that have been done in a particular area of interest. When examining and summarizing the literature, researchers are expected to determine which of the studies were well-conducted (i.e. high quality) and those that were not. What we do not know enough about is how researchers should conduct the assessments to determine which studies were of high quality. This is important because if the researcher is aware of certain study characteristics (e.g. what journal the study was published in) they may inadvertently assess the study a certain way. For example, if the author of the study is well-known to the assessor, they may be more likely to assume it is of 'high quality'. Our research examines whether blinding researchers to study characteristics makes a difference when the goal is to summarize the literature. We only found a few studies that reported data relevant to our question. The results from these studies were inconsistent, however, the results suggest that it may not make a difference if quality is appraised under blinded or unblinded conditions during a systematic review. |
With 8 studies added in this update, 17 met our inclusion criteria and had a total of 63,813 women. We focus here on 12 studies that provided high, moderate, or low quality evidence. Most did not show a higher pregnancy risk among overweight or obese women. Of five COC studies, two found BMI to be associated with pregnancy but in different directions. With an OC containing norethindrone acetate and ethinyl estradiol (EE), pregnancy risk was higher for overweight women, i.e. with BMI ≥ 25 versus those with BMI < 25 (reported relative risk 2.49, 95% CI 1.01 to 6.13). In contrast, a trial using an OC with levonorgestrel and EE reported a Pearl Index of 0 for obese women (BMI ≥ 30) versus 5.59 for nonobese women (BMI < 30). The same trial tested a transdermal patch containing levonorgestrel and EE. Within the patch group, obese women in the "treatment-compliant" subgroup had a higher reported Pearl Index than nonobese women (4.63 versus 2.15). Of five implant studies, two that examined the six-capsule levonorgestrel implant showed differences in pregnancy by weight. One study showed higher weight was associated with higher pregnancy rate in years 6 and 7 combined (reported P < 0.05). In the other, pregnancy rates differed in year 5 among the lower weight groups only (reported P < 0.01) and did not involve women weighing 70 kg or more. Analysis of data from other contraceptive methods indicated no association of pregnancy with overweight or obesity. These included depot medroxyprogesterone acetate (subcutaneous), levonorgestrel IUC, the two-rod levonorgestrel implant, and the etonogestrel implant. The evidence generally did not indicate an association between higher BMI or weight and effectiveness of hormonal contraceptives. However, we found few studies for most contraceptive methods. Studies using BMI, rather than weight alone, can provide information about whether body composition is related to contraceptive effectiveness. The contraceptive methods examined here are among the most effective when used according to the recommended regimen. We considered the overall quality of evidence to be low for the objectives of this review. More recent reports provided evidence of varying quality, while the quality was generally low for older studies. For many trials the quality would be higher for their original purpose rather than the non-randomized comparisons here. Investigators should consider adjusting for potential confounding related to BMI or contraceptive effectiveness. Newer studies included a greater proportion of overweight or obese women, which helps in examining effectiveness and side effects of hormonal contraceptives within those groups. | Until 4 August 2016, we did computer searches for studies of hormonal birth control among women who were overweight or obese. We looked for studies that compared overweight or obese women with women of normal weight or body mass index (BMI). The formula for BMI is weight (kg) / height (m)2. We included all study designs. For the original review, we wrote to investigators to find other studies we might have missed. With 8 studies added in this update, we had 17 with a total of 63,813 women. We focus here on 12 studies with high, moderate, or low quality results. Most did not show more pregnancies for overweight or obese women. Two of five studies using birth control pills found differences between BMI groups. In one, overweight women had a higher pregnancy risk. The other found a lower pregnancy rate for obese women versus nonobese women. The second study also tested a new skin patch. Obese women in the patch group had a higher pregnancy rate. Of five implant studies, two showed differences among weight groups. They studied the older six-capsule implant. One study showed a higher pregnancy rate in years 6 and 7 combined for women weighing 70 kg or more. The other reported pregnancy differences in year 5 among the lower weight groups only. Results for other methods of birth control did not show overweight or obesity related to pregnancy rate. Those methods included an injectable, hormonal IUC, and the two-rod and single-rod implants. These studies generally did not show an association of BMI or weight with the effect of hormonal methods. We found few studies for most methods. Studies using BMI rather than weight can show whether body fat is related to how well birth control prevents pregnancy. The methods studied here work very well when used according to directions. The overall study quality was low for this review, especially in the older reports. However, many studies would have higher quality for their original purpose than for the comparisons here. |
Seven randomised trials were included, four of which reported usable data on 472 children with asthma one to 18 years of age who were admitted to paediatric wards. No trials included patients admitted to the ICU. The anticholinergic used, ipratropium bromide 250 μg, was given every one to eight hours over a period from four hours to the entire length of the hospital stay. Two of four trials (50%) contributing data were deemed of high methodological quality. The addition of anticholinergics to β2-agonists showed no evidence of effect on the duration of hospital admission (mean difference (MD) -0.28 hours, 95% confidence interval (CI) -5.07 to 4.52, 3 studies, 327 participants, moderate quality evidence) and no serious or non-serious adverse events were reported in any included trials. As a result of the similarity of trials, we could not explore the influence of age, admission site, intensity of anticholinergic treatment and co-interventions on primary outcomes. No statistically significant group difference was noted in other secondary outcomes, including the need for supplemental asthma therapy, time to short-acting β2-agonists spaced at four hours or longer, asthma clinical scores, lung function and overall withdrawals for any reason. In children hospitalised for an acute asthma exacerbation, no evidence of benefit for length of hospital stay and other markers of response to therapy was noted when nebulised anticholinergics were added to short-acting β2-agonists. No adverse health effects were reported, yet the small number of trials combined with inadequate reporting prevent firm reassurance regarding the safety of anticholinergics. In the absence of trials conducted in ICUs, no conclusion can be drawn regarding children with impending respiratory failure. These findings support current national and international recommendations indicating that healthcare practitioners should refrain from using anticholinergics in children hospitalised for acute asthma. | In reviewing evidence available until November 2013, we found seven eligible studies of children hospitalised with acute asthma; four of these studies (472 children one to 18 years of age) contributed data to the review. Four studies compared the combination of anticholinergics (ipratropium bromide) and beta2-agonists versus the same dose of beta2-agonists alone. Included studies enrolled both girls and boys, with a gender ratio ranging from 59% to 73% males. No additional benefit was noted by adding anticholinergics to β2-agonists in terms of duration of hospital stay in patients compared to those who received beta2-agonists alone. Two of four trials (50%) contributing data were deemed of high methodological quality. No trial reported information on serious adverse events. No statistically significant group difference was noted in other markers of response to therapy, that is, the need for supplemental asthma therapy, time to short-acting beta2-agonists spaced at four hours or longer, asthma clinical scores, lung function and overall withdrawals for any reason. No apparent benefit is derived from adding anticholinergics to beta2-agonists in children hospitalised for an acute asthma exacerbation, that is, beyond initial treatment in the emergency department. No adverse health effects were reported, yet the small number of trials combined with inadequate reporting prevents firm reassurance regarding the safety of anticholinergics. In the absence of trials conducted in the intensive care unit (ICU), no conclusion can be drawn regarding children with very severe exacerbations who are admitted to the ICU. Our findings support the ongoing recommendations provided by national and international guidelines. This review is based on a small number of identified trials conducted in children with acute asthma. All trials contributing to the primary outcome are of high methodological quality, but they are few. As the addition of new trials may change the conclusion, the quality of evidence was downgraded from high to moderate. Additional and larger trials are needed. |
We identified six randomised comtrolled trials of auditory integration therapy and one of Tomatis therapy, involving a total of 182 individuals aged three to 39 years. Two were cross-over trials. Five trials had fewer than 20 participants. Allocation concealment was inadequate for all studies. Twenty different outcome measures were used and only two outcomes were used by three or more studies. Meta-analysis was not possible due to very high heterogeneity or the presentation of data in unusable forms. Three studies (Bettison 1996; Zollweg 1997; Mudford 2000) did not demonstrate any benefit of auditory integration therapy over control conditions. Three studies (Veale 1993; Rimland 1995; Edelson 1999) reported improvements at three months for the auditory integration therapy group based on the Aberrant Behaviour Checklist, but they used a total score rather than subgroup scores, which is of questionable validity, and Veale's results did not reach statistical significance. Rimland 1995 also reported improvements at three months in the auditory integration therapy group for the Aberrant Behaviour Checklist subgroup scores. The study addressing Tomatis therapy (Corbett 2008) described an improvement in language with no difference between treatment and control conditions and did not report on the behavioural outcomes that were used in the auditory integration therapy trials. There is no evidence that auditory integration therapy or other sound therapies are effective as treatments for autism spectrum disorders. As synthesis of existing data has been limited by the disparate outcome measures used between studies, there is not sufficient evidence to prove that this treatment is not effective. However, of the seven studies including 182 participants that have been reported to date, only two (with an author in common), involving a total of 35 participants, report statistically significant improvements in the auditory intergration therapy group and for only two outcome measures (Aberrant Behaviour Checklist and Fisher's Auditory Problems Checklist). As such, there is no evidence to support the use of auditory integration therapy at this time. | The purpose of this review was to assess the evidence for the effectiveness of auditory integration therapy and therapies like it that have been developed to improve abnormal sound sensitivity and autistic behaviours in such individuals. Seven relatively small studies met the inclusion criteria for the review. These often measured different outcomes and reported mixed results. Benefits for participants receiving auditory integration therapy were only reported in two studies, involving 35 participants, for two outcomes. A study of Tomatis therapy did not measure behavioural outcomes and did not find any difference in language development between intervention and control groups. As such, there is no evidence to support the use of auditory integration therapy or other sound therapies at this time. |
We identified 18 potential studies, of which two, currently reported only as abstracts, met the inclusion criteria for this review. Too little information was available for us to present full results or adequately assess risk of bias. The participants were children aged five to 15 years with DMD, ambulant and non-ambulant. The interventions were risedronate versus no treatment in one trial (13 participants) and whole-body vibration versus a placebo device in the second (21 participants). Both studies reported improved bone mineral density with the active treatments, with no improvement in the control groups, but the abstracts did not compare treatment and control conditions. All children tolerated whole-body vibration treatment. No study provided information on adverse events. Two studies are ongoing: one investigating whole-body vibration, the other investigating zoledronic acid. We know of no high-quality evidence from RCTs to guide use of treatments to prevent or treat corticosteroid-induced osteoporosis and reduce the risk of fragility fractures in children and adults with DMD; only limited results from two trials reported in abstracts were available. We await formal trial reports. Findings from two ongoing relevant studies and two trials, for which only abstracts are available, will be important in future updates of this review. | We searched the medical literature comprehensively, finding two completed trials. Only brief reports (abstracts) of these trials are available. The participants were children aged from five to 15 years with DMD who were able to walk and not able to walk. The treatments were risedronate versus no treatment in one trial (with 13 participants) and whole-body vibration versus a placebo (inactive) device in the other (with 21 participants). We found two completed studies that were potentially eligible for this review, for which full results have not yet been published, and two studies ongoing at the time of the search. These studies are looking at the effects of whole-body vibration (two studies), risedronate, and zoledronic acid. Both completed trials, presented as abstracts only, reported an improvement in bone mineral density in children who received active treatment and no improvement in children in the control (placebo or no treatment) groups. However, the reports did not report results for the comparison of treatment versus control groups, which means that it is not possible to draw conclusions about the effectiveness of either treatment. All children tolerated whole-body vibration treatment. Neither study provided information on adverse events. We know of no evidence from randomised clinical trials to guide use of treatments to prevent or treat osteoporosis and prevent fragility fractures in people with DMD taking corticosteroids. Searches are current to September 2016. |
We found six randomised, double-blind trials of at least two weeks' duration eligible for inclusion. These trials included 460 participants with neuropathic pain, with most participants having painful diabetic neuropathy. Four studies were of cross-over design and two were parallel trials. Only one trial was both parallel design and placebo-controlled. Mean age of participants ranged from 48 to 59 years. In three studies (Forssell 2004, Jia 2006 and Tasmuth 2002), only mean data were reported. Comparators included placebo, imipramine, and carbamazepine and duration of treatment ranged from two to eight weeks. The risk of bias was considerable overall in the review, especially due to the small size of most studies and due to attrition bias. Four of the six studies reported some positive benefit for venlafaxine. In the largest study by Rowbotham, 2004, 56% of participants receiving venlafaxine 150 to 225 mg achieved at least a 50% reduction in pain intensity versus 34% of participants in the placebo group and the number needed to treat for an additional beneficial outcome was 4.5. However, this study was subject to significant selection bias. Known adverse effects of venlafaxine, including somnolence, dizziness, and mild gastrointestinal problems, were reported in all studies but were not particularly problematic and, overall, adverse effects were equally prominent in placebo or other active comparator groups. We found little compelling evidence to support the use of venlafaxine in neuropathic pain. While there was some third-tier evidence of benefit, this arose from studies that had methodological limitations and considerable risk of bias. Placebo effects were notably strong in several studies. Given that effective drug treatments for neuropathic pain are in current use, there is no evidence to revise prescribing guidelines to promote the use of venlafaxine in neuropathic pain. Although venlafaxine was generally reasonably well tolerated, there was some evidence that it can precipitate fatigue, somnolence, nausea, and dizziness in a minority of people. | In detailed searches of the medical literature, we found six trials that were suitable for inclusion in our analysis, that together included 460 adults. All six trials were conducted in an approved statistical manner (randomised and double-blinded); however, all had limitations that could lead to an overestimation of efficacy in treating this type of pain. Four were of very small size and five were of short duration, both of which can bias the results of chronic pain trials. Although it was not possible to combine the results of all trials to make an overall conclusion, individually they did all show some, albeit moderate, benefit for venlafaxine in treating neuropathic pain. Usually this benefit was achieved at doses of 75 to 225 mg per day. Known side effects of venlafaxine, including sleepiness, dizziness, and mild gastrointestinal problems, were reported by some studies, but were not particularly problematic. Overall, there is currently an inadequate amount of information available to warrant any change in current prescribing practice and we cannot recommend venlafaxine as a first-line treatment for neuropathic pain. However, it is a reasonably well-tolerated drug and may be of some benefit in people who cannot tolerate other antidepressants or anticonvulsant drugs that are more widely prescribed to people with neuropathic pain. Larger clinical trials may provide more robust evidence for the effectiveness of venlafaxine in treating neuropathic pain. |
We included four trials, with a combined total of 1439 women in the review; each trial examined a different method of induction and we were unable to pool the results from trials. 1. Vaginal PGE2 (two studies including 1028 women). There were no differences between women managed as outpatients versus inpatients for most review outcomes. There was no evidence of a difference between the likelihood of women requiring instrumental delivery in either setting (risk ratio (RR) 1.29; 95% confidence interval (CI) 0.79 to 2.13). The overall length of hospital stay was similar in the two groups. 2. Controlled release PGE2 10 mg (one study including 300 women). There was no evidence of differences between groups for most review outcomes, including success of induction. During the induction period itself, women in the outpatient group were more likely to report high levels of satisfaction with their care (satisfaction rated seven or more on a nine-point scale, RR 1.42; 95% CI 1.11 to 1.81), but satisfaction scores measured postnatally were similar in the two groups. 3. Foley catheter (one study including 111 women). There was no evidence of differences between groups for caesarean section rates, total induction time and the numbers of babies admitted to neonatal intensive care. The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings. | Four randomised controlled trials with a combined total of 1439 women assessed the effects of induction of labour for women managed as outpatients versus inpatients. Out of a total of four studies, the induction agents differed in two studies, whereas the remaining two studies evaluated the same induction agent (vaginal PGE2). The limited information from these trials did not support more successful induction within 24 hours, shorter length of stay in hospital or differences in need for further induction or the mode of giving birth. The information available was limited and it is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings. |
In this update, we included three trials involving 1398 postoperative participants. Participants were submitted to general surgical procedures, minor and major, and the minimum mean age was 49 years. Pooled analysis showed a significant reduction in the risk of HIT with LMWH compared with UFH (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.07 to 0.73); low-quality evidence. The number needed to treat for an additional beneficial outcome (NNTB) was 59. The risk of HIT was consistently reduced comparing participants undergoing major surgical procedures exposed to LMWH or UFH (RR 0.22, 95% CI 0.06 to 0.75); low-quality evidence. The occurrence of HIT complicated by venous thromboembolism was significantly lower in participants receiving LMWH compared with UFH (RR 0.22, 95% CI 0.06 to 0.84); low-quality evidence. The NNTB was 75. Arterial thrombosis occurred in only one participant who received UFH. There were no amputations or deaths documented. Although limited evidence is available, it appears that HIT induced by both types of heparins is common in people undergoing major surgical procedures (incidence greater than 1% and less than 10%). This updated review demonstrated low-quality evidence of a lower incidence of HIT, and HIT complicated by venous thromboembolism, in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. Similarily, the risk of HIT in people undergoing major surgical procedures was lower when treated with LMWH compared to UFH (low-quality evidence). The quality of the evidence was downgraded due to concerns about the risk of bias in the included studies and imprecision of the study results. These findings may support current clinical use of LMWH over UFH as front-line heparin therapy. However, our conclusions are limited and there was an unexpected paucity of RCTs including HIT as an outcome. To address the scarcity of clinically-relevant information on HIT, HIT must be included as a core harmful outcome in future RCTs of heparin. | The evidence gathered in this review was considered of low quality. We downgraded the quality of the evidence because we had concerns about the risk of bias in the included studies and imprecision of the results. It was possible that patient prognosis or clinicians' preferences influenced the allocation of participants to receive one or another medication. This process should be implemented by chance to allow a fair comparison between the therapies. We were not confident that staff implementing the trials were not aware of which treatment participants were receiving, and it was possible that the incomplete reporting of data could have affected the estimates. The detection of HIT throughout the trials was also problematic, and we were not confident that it was performed adequately. The results may be correct, but they may be changed by future research. |
Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near-patient influenza testing were included. Of these 2356 children, 1255 had laboratory-confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory-confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir-resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory-confirmed influenza (risk difference (RD) -0.14, 95% confidence interval (CI) -0.24 to -0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD -0.08, 95% CI -0.12 to -0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar. Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups. | This update reviews the randomised controlled trial evidence of a class of drugs called the neuraminidase inhibitors in treating and preventing influenza in children. Neuraminidase inhibitors work against influenza by preventing viruses from being released from infected cells and subsequently infecting further cells. Oseltamivir (Tamiflu), an oral medication, and zanamivir (Relenza), an inhaled medication, are currently licensed, whilst laninamivir is undergoing Phase III clinical trials. Neuraminidase inhibitors are usually prescribed to patients presenting with flu-like symptoms during epidemic periods to reduce symptoms or prevent spread of the virus. We included six treatment trials involving 1906 children with clinically suspected influenza and 450 children with influenza diagnosed on rapid influenza testing. Of these 2356 children, 1255 had proven influenza infection confirmed on laboratory testing. We also included three trials of neuraminidase inhibitors for the prevention of influenza, which involved 863 children who had been exposed to influenza. This review found that treatment with neuraminidase inhibitors was only associated with modest clinical benefit in children with proven influenza. Treatment with oseltamivir or zanamivir shortened the duration of illness in healthy children by about one day. One trial demonstrated that the new neuraminidase inhibitor drug laninamivir reduces duration of illness by almost three days in children with oseltamivir-resistant influenza. The effect of neuraminidase inhibitors in preventing transmission of influenza was also modest; 13 children would need to be treated to prevent one additional case. Neuraminidase inhibitors are generally well tolerated but there will be one extra case of vomiting for every 17 children treated with oseltamivir. Other side effects such as diarrhoea and nausea were no more common in children treated with neuraminidase inhibitors compared to placebo. There is currently no high-quality evidence to support targeted treatment of 'at risk' children (with underlying chronic medical conditions) with neuraminidase inhibitors. |
Four studies (199 participants) met the inclusion criteria and were predominantly conducted in children with cystic fibrosis. Only one study had a combined cohort of adult and paediatric participants. The description of study methods was inadequate to assess the risk of bias, particularly with regard to blinding of assessors and selective reporting. One study was conducted in an inpatient setting with follow up in the outpatient setting; while the remaining three studies were conducted in individuals with stable respiratory disease in the outpatient setting. All included studies used exercise training to promote participation in physical activity, with the duration of the intervention period ranging from 18 days to three years. No improvement in physical activity participation was reported with any intervention period less than or equal to six months. Improvements in physical activity participation were only seen where follow up occurred beyond 12 months. There was no significant impact on quality of life from any of the intervention strategies. Although participation in physical activity is generally regarded as beneficial for people with cystic fibrosis, there is a lack of evidence regarding strategies to promote the uptake and the continued participation in physical activity for this population. This review provides very limited evidence that activity counselling and exercise advice, undertaken over at least six months, to engage in a home exercise programme may result in improved physical activity participation in people with cystic fibrosis. Further research is needed to determine the effect of strategies such as health coaching or telemedicine applications, in promoting the uptake and adherence to regular participation in physical activity. In addition, establishing the ideal duration of any interventions that promote physical activity, including exercise training programmes, will be important in addressing issues relating to participation in physical activity for people with cystic fibrosis. | This review aimed to evaluate the strategies that encourage people with cystic fibrosis to participate in daily physical activity. There were four included studies with a total of 199 participants which investigated the effect of exercise training on participation in physical activity. These were mostly conducted in children. The study methods and results were not clearly reported, so it was difficult to tell if the results were influenced by the way in which participants were assessed, or the nature of the outcomes reported. The training programmes ranged from 18 days to three years. In two studies the exercise training programmes were supervised and in two studies they were unsupervised and home-based. Due to differences in the study design and the outcomes measured, we could not combine data from different studies. None of the studies reported any improvement in participation in physical activity when the exercise training lasted less than six months. There was very limited evidence that using a home-exercise programme, for at least six months after receiving activity counselling and exercise advice, improved participation in physical activity in people with cystic fibrosis. No training program showed significant effects on quality of life. It is unknown whether strategies such as health coaching or Internet-based advice may help promote regular participation in physical activity in people with cystic fibrosis. |
Results of only a limited number of studies could be combined, in view of different types of interventions and variable quality of data. We found six trials of proprietary herbal mixtures and one of whole system Ayurvedic treatment. These studies enrolled 354 participants ( 172 on treatment, 158 on controls, 24 allocation unknown). The treatment duration ranged from 3 to 6 months. All these studies included adults with type 2 diabetes mellitus. With regard to our primary outcomes, significant reductions in glycosylated haemoglobin A1c (HbA1c), fasting blood sugar (FBS) or both were observed with Diabecon, Inolter and Cogent DB compared to placebo or no additional treatment, while no significant hypoglycaemic response was found with Pancreas tonic and Hyponidd treatment. The study of whole system Ayurvedic treatment did not provide data on HbA1c and FBS values. One study of Pancreas tonic treatment did not detect a significant change in health-related quality of life. The main adverse effects reported were drug hypersensitivity (one study, one patient in the treatment arm); hypoglycaemic episodes (one study, one participant in the treatment arm; none had severe hypoglycaemia) and gastrointestinal side effects in one study (1 of 20 in the intervention group and 0 of 20 participants in the control group). None of the included studies reported any deaths, renal, hematological or liver toxicity. With regard to our secondary outcomes, post prandial blood sugar (PPBS) was lower among participants treated with Diabecon, was unchanged with Hyponidd and was higher in patients treated with Cogent DB. Treatment with Pancreas tonic and Hyponidd did not affect lipid profile significantly, while patients treated with Inolter had significantly higher HDL- and lower LDL-cholesterol as well as lower triglycerides. Cogent DB treated participants also had lower total cholesterol and triglycerides. Studies of treatment with Diabecon reported increased fasting insulin levels; one study of treatment with Diabecon reported higher stimulated insulin levels and fasting C-peptide levels in the treatment group. There was no significant difference in fasting and stimulated C-peptide and insulin levels with Hyponidd, Cogent DB and Pancreas tonic treatment. The study of Inolter did not assess these outcomes. No study reported on or was designed to investigate diabetic complications, death from any cause and economic data. Although there were significant glucose-lowering effects with the use of some herbal mixtures, due to methodological deficiencies and small sample sizes we are unable to draw any definite conclusions regarding their efficacy. Though no significant adverse events were reported, there is insufficient evidence at present to recommend the use of these interventions in routine clinical practice and further studies are needed. | This review examines the efficacy and safety of the use of various Ayurvedic treatments for diabetes mellitus. We found seven trials which included 354 participants (172 on treatment, 158 on control, 24 could not be classified). All these studies included adults with type 2 diabetes mellitus. Six studies tested five different types of herbal mixtures (proprietary drugs) and only one tested 'whole system' Ayurvedic treatment. The duration of treatment ranged from three to six months. One study each of Diabecon, Inolter and Cogent DB (proprietary herbal mixtures) found significantly lower glycosylated haemoglobin A1c (HbA1C) levels at the end of the treatment period compared to controls. Two studies of Diabecon, and one study of Cogent DB (proprietary herbal mixtures) found significantly lower fasting blood sugar levels at the end of the study period in the treatment group. No deaths were observed in these trials and side effects did not differ significantly between intervention and control groups. One study of Pancreas tonic reported no significant change in health-related quality of life. No study reported on or was designed to investigate diabetic complications, death from any cause and costs. Despite positive results in some studies, and absence of serious side effects, firm conclusions cannot be drawn due to weak methods and small number of participants in the evaluated studies. Further research is needed to assess the efficacy of these treatments. Ayurvedic physicians generally use a mixture of various herbs or proprietary preparations along with diet, exercise and mode of living. The treatments are usually individualised taking into account the balance of three 'doshas'. It is possible that the interventions in the trials analysed have not replicated actual Ayurvedic practice but only assessed some components individually. |
108 trials were located using the specified search strategy in 2001. An additional three trials were located when the search strategy was repeated in 2004. Of the total number of trials located in both searches, only two trials, involving a total of 64 patients, were of sufficient quality to meet inclusion criteria. The available evidence suggests these substances were better than placebo at alleviating depression (Peto Odds Ratio 4.10; 95% confidence interval 1.28-13.15; RD 0.36; NNT 2.78). However, the evidence was of insufficient quality to be conclusive. A large number of studies appear to address the research questions, but few are of sufficient quality to be reliable. Available evidence does suggest these substances are better than placebo at alleviating depression. Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended. The possible association between these substances and the potentially fatal Eosinophilia-Myalgia Syndrome has not been elucidated. Because alternative antidepressants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present. | Until then, the reviewers propose that the use of antidepressants which have no known life threatening side effects remain more attractive. The review sets out the required methodology for effectively studying these substances in proper controlled studies. |
We included 15 studies (1722 participants) in the review. There are also four ongoing studies and four studies await classification. The 15 included studies evaluated four comparisons: removable retainers versus fixed retainers (three studies); different types of fixed retainers (four studies); different types of removable retainers (eight studies); and one study compared a combination of upper thermoplastic and lower bonded versus upper thermoplastic with lower adjunctive procedures versus positioner. Four studies had a low risk of bias, four studies had an unclear risk of bias and seven studies had a high risk of bias. Removable versus fixed retainers Thermoplastic removable retainers provided slightly poorer stability in the lower arch than multistrand fixed retainers: MD (Little's Irregularity Index, 0 mm is stable) 0.6 mm (95% CI 0.17 to 1.03). This was based on one trial with 84 participants that was at high risk of bias; it was low quality evidence. Results on retainer failure were inconsistent. There was evidence of less gingival bleeding with removable retainers: RR 0.53 (95% CI 0.31 to 0.88; one trial, 84 participants, high risk of bias, low quality evidence), but participants found fixed retainers more acceptable to wear, with a mean difference on a visual analogue scale (VAS; 0 to 100; 100 being very satisfied) of -12.84 (95% CI -7.09 to -18.60). Fixed versus fixed retainers The studies did not report stability, adverse effects or participant satisfaction. It was possible to pool the data on retention failure from three trials that compared polyethylene ribbon bonded retainer versus multistrand retainer in the lower arch with an RR of 1.10 (95% CI 0.77 to 1.57; moderate heterogeneity; three trials, 228 participants, low quality evidence). There was no evidence of a difference in failure rates. It was also possible to pool the data from two trials that compared the same types of upper fixed retainers, with a similar finding: RR 1.25 (95% CI 0.87 to 1.78; low heterogeneity; two trials, 174 participants, low quality evidence). Removable versus removable retainers One study at low risk of bias comparing upper and lower part-time thermoplastic versus full-time thermoplastic retainer showed no evidence of a difference in relapse (graded moderate quality evidence). Another study, comparing part-time and full-time wear of lower Hawley retainers, found no evidence of any difference in relapse (low quality evidence). Two studies at high risk of bias suggested that stability was better in the lower arch for thermoplastic retainers versus Hawley, and for thermoplastic full-time versus Begg (full-time) (both low quality evidence). In one study, participants wearing Hawley retainers reported more embarrassment more often than participants wearing thermoplastic retainers: RR 2.42 (95% CI 1.30 to 4.49; one trial, 348 participants, high risk of bias, low quality evidence). They also found Hawley retainers harder to wear. There was conflicting evidence about survival rates of Hawley and thermoplastic retainers. Other retainer comparisons Another study with a low risk of bias looked at three different approaches to retention for people with crowding, but normal jaw relationships. The study found that there was no evidence of a difference in relapse between the combination of an upper thermoplastic and lower canine to canine bonded retainer and the combination of an upper thermoplastic retainer and lower interproximal stripping, without a lower retainer. Both these approaches are better than using a positioner as a retainer. We did not find any evidence that wearing thermoplastic retainers full-time provides greater stability than wearing them part-time, but this was assessed in only a small number of participants. Overall, there is insufficient high quality evidence to make recommendations on retention procedures for stabilising tooth position after treatment with orthodontic braces. Further high quality RCTs are needed. | We searched scientific databases to find all the new evidence up to 26 January 2016. This review updates a previous one published in 2006. We included 15 studies that compared different types of fixed and removable retainers and different durations of wear. There were 1722 participants including adults and children. Nine studies took place in a hospital or university setting, five studies in specialist practice and one in a National Health Service Clinic. The studies evaluated four comparisons: removable retainers versus fixed retainers (three studies); different types of fixed retainers (four studies); different types of removable retainers (eight studies); and one study compared a combination of removable and fixed retainers, use of an adjunctive procedure and a positioner. We also found four ongoing studies and four studies await classification. Most of the evidence was of low quality. One small but well conducted study that compared full-time and part-time wear of thermoplastic retainers did not find evidence of a difference in stability (moderate quality evidence). There is not enough high quality evidence to recommend any one approach to retention over another. Further high-quality studies are needed. |
We included four RCTs involving 758 participants. We did not pool data because of heterogeneity in study designs, outcomes and time points. The studies provided sparse information about effects longer than a few hours, as three of four included studies were short trials of only four to six hours. Participants treated with acetaminophen had significant improvements in nasal obstruction in two of the four studies. One study showed that acetaminophen was superior to placebo in decreasing rhinorrhoea severity, but was not superior for treating sneezing and coughing. Acetaminophen did not improve sore throat or malaise in two of the four studies. Results were inconsistent for some symptoms. Two studies showed that headache and achiness improved more in the acetaminophen group than in the placebo group, while one study showed no difference between the acetaminophen and placebo group. None of the included studies reported the duration of common cold symptoms. Minor side effects (including gastrointestinal adverse events, dizziness, dry mouth, somnolence and increased sweating) in the acetaminophen group were reported in two of the four studies. One of them used a combination of pseudoephedrine and acetaminophen. Acetaminophen may help relieve nasal obstruction and rhinorrhoea but does not appear to improve some other cold symptoms (including sore throat, malaise, sneezing and cough). However, two of the four included studies in this review were small and allocation concealment was unclear in all four studies. The data in this review do not provide sufficient evidence to inform practice regarding the use of acetaminophen for the common cold in adults. Further large-scale, well-designed trials are needed to determine whether this intervention is beneficial in the treatment of adults with the common cold. | We identified four trials that included 758 participants. We excluded studies in which the participants had complications. Two of the four included studies in this review were small and the quality of the evidence was low to moderate. We do not know if acetaminophen is effective for reducing common cold symptoms or its adverse effects. We cannot either 'recommend' or 'not recommend' its use in common practice because we do not have enough well-designed trials to reach a conclusion. There is a need for more high-quality studies to determine the effectiveness of acetaminophen in relieving common cold symptoms. |
Thirty-one published RCTs of all forms of surgical treatment for degenerative lumbar spondylosis were identified. The trials varied in quality: only the more recent trials used appropriate methods of randomization, blinding and independent assessment of outcome. Most of the earlier published results were of technical surgical outcomes with some crude ratings of clinical outcome. More of the recent trials also reported patient-centered outcomes of pain or disability, but there is still very little information on occupational outcomes. There was a particular lack of long term outcomes beyond two to three years. Seven heterogeneous trials on spondylolisthesis, spinal stenosis and nerve compression permitted limited conclusions. Two new trials on the effectiveness of fusion showed conflicting results. One showed that fusion gave better clinical outcomes than conventional physiotherapy, while the other showed that fusion was no better than a modern exercise and rehabilitation programme. Eight trials showed that instrumented fusion produced a higher fusion rate (though that needs to be qualified by the difficulty of assessing fusion in the presence of metal-work), but any improvement in clinical outcomes is probably marginal, while there is other evidence that it may be associated with higher complication rates. Three trials with conflicting results did not permit any conclusions about the relative effectiveness of anterior, posterior or circumferential fusion. Preliminary results of two small trials of intra-discal electrotherapy showed conflicting results. Preliminary data from three trials of disc arthroplasty did not permit any firm conclusions. Limited evidence is now available to support some aspects of surgical practice. Surgeons should be encouraged to perform further RCTs in this field. | This review considers the available evidence on the procedures of spinal decompression (widening the spinal canal or laminectomy), nerve root decompression (of one or more individual nerves) and fusion of adjacent vertebrae. There is moderate evidence that instrumentation can increase the fusion rate, but any improvement in clinical outcomes is probably marginal. The effectiveness of intra-discal electrotherapy (IDET) remains unproven. Only preliminary results are available on disc replacement and it is not possible to draw any conclusions on this subject. |
We did not identify any new trials from the updated search so the results remain unchanged as follows. We included four trials involving 852 women. Three trials (involving 500 women) evaluating the effects of IAP versus no treatment were included. The use of IAP did not significantly reduce the incidence of all cause mortality, mortality from GBS infection or from infections caused by bacteria other than GBS. The incidence of early GBS infection was reduced with IAP compared to no treatment (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.04 to 0.74, three trials, 488 infants; risk difference -0.04, 95% CI -0.07 to -0.01; number needed to treat to benefit 25, 95% CI 14 to 100, I² 0%). The incidence of LOD or sepsis from organisms other than GBS and puerperal infection was not significantly different between groups. One trial (involving 352 women) compared intrapartum ampicillin versus penicillin and reported no significant difference in neonatal or maternal outcomes. We found a high risk of bias for one or more key domains in the study methodology and execution. Intrapartum antibiotic prophylaxis appeared to reduce EOGBSD, but this result may well be due to bias as we found a high risk of bias for one or more key domains in the study methodology and execution. There is lack of evidence from well designed and conducted trials to recommend IAP to reduce neonatal EOGBSD. Ideally the effectiveness of IAP to reduce neonatal GBS infections should be studied in adequately sized double-blind controlled trials. The opportunity to conduct such trials has likely been lost, as practice guidelines (albeit without good evidence) have been introduced in many jurisdictions. | This review finds that giving antibiotics is not supported by conclusive evidence. The review identified four trials involving 852 GBS positive women. Three trials, which were more than 20 years old, compared ampicillin or penicillin to no treatment and found no clear differences in newborn deaths although the occurrence of early GBS infection in the newborn was reduced with antibiotics. The antibiotics ampicillin and penicillin were no different from each other in one trial with 352 GBS positive women. All cases of perinatal GBS infections are unlikely to be prevented even if an effective vaccine is developed. |
One hundred and eighteen studies with 138 treatment groups and 17,364 participants were included in this review. Fifty-seven of these studies were included in the original version of this review while 61 were added, including 27 on interventions that were not considered in the original version. Interventions included amiodarone, beta-blockers, sotalol, magnesium, atrial pacing and posterior pericardiotomy. Each of the studied interventions significantly reduced the rate of post-operative atrial fibrillation after cardiac surgery compared with a control. Beta-blockers (odds ratio (OR) 0.33; 95% confidence interval) CI 0.26 to 0.43; I2 = 55%) and sotalol (OR 0.34; 95% CI 0.26 to 0.43; I2 = 3%) appear to have similar efficacy while magnesium's efficacy (OR 0.55; 95% CI 0.41 to 0.73; I2 = 51%) may be slightly less. Amiodarone (OR 0.43; 95% CI 0.34 to 0.54; I2 = 63%), atrial pacing (OR 0.47; 95% CI 0.36 to 0.61; I2 = 50%) and posterior pericardiotomy (OR 0.35; 95% CI 0.18 to 0.67; I2 = 66%) were all found to be effective. Prophylactic intervention decreased the hospital length of stay by approximately two-thirds of a day and decreased the cost of hospital treatment by roughly $1250 US. Intervention was also found to reduce the odds of post-operative stroke, though this reduction did not reach statistical significance (OR 0.69; 95% CI 0.47 to 1.01; I2 = 0%). No significant effect on all-cause or cardiovascular mortality was demonstrated. Prophylaxis to prevent atrial fibrillation after cardiac surgery with any of the studied pharmacological or non-pharmacological interventions may be favored because of its reduction in the rate of atrial fibrillation, decrease in the length of stay and cost of hospital treatment and a possible decrease in the rate of stroke. However, this review is limited by the quality of the available data and heterogeneity between the included studies. Selection of appropriate interventions may depend on the individual patient situation and should take into consideration adverse effects and the cost associated with each approach. | Atrial fibrillation after heart surgery is a common complication that has been associated with poor outcomes. We reviewed the literature to better understand the role of preventative interventions for this condition. By combining the results of 118 studies with 17,364 participants, we are able to gain a better understanding of the evidence behind each of these interventions. All of the interventions studied were effective in reducing the occurrence of atrial fibrillation, length of hospital stay, cost of hospital treatment and may be effective in reducing the risk of stroke. The interventions did not have an effect on death after heart surgery. It was not possible to analyze the adverse events associated with the medications studied in this review, but these should be considered by clinicians when choosing an appropriate intervention for their patients. Furthermore, differences in the design between the studies combined in this review may complicate interpretation of these results. |
We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant. In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence). The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted. | We included five trials with a total of 122 participants. In these trials the length of treatment ranged from two to eight weeks. Four of the trials compared inhaling before to inhaling after the airways had been cleared and found no overall difference in clinical outcomes. However, in children with well-preserved lung function, inhaling of dornase alfa after airway clearance techniques was better for small airways function. However, this did not affect quality of life or other outcomes. In the remaining trial, morning versus evening inhalation had no impact on lung function or symptoms. Therefore, for many people with cystic fibrosis, the timing of dornase alfa inhalation (before or after airway clearance or the time of day) can be based on practical reasons or individual preference. Apart from one trial published only in abstract form, the quality of the evidence ranged from low to very low. This was due to issues relating to group allocation, blinding, incomplete reporting of outcome data and the the limited age range of participants. |
Sixty-six trials met our inclusion criteria for one or more of the comparisons in the review. Thirteen trials compared a group programme with a self-help programme; there was an increase in cessation with the use of a group programme (N = 4395, risk ratio (RR) 1.88, 95% confidence interval (CI) 1.52 to 2.33, I2 = 0%). We judged the GRADE quality of evidence to be moderate, downgraded due to there being few studies at low risk of bias. Fourteen trials compared a group programme with brief support from a health care provider. There was a small increase in cessation (N = 7286, RR 1.22, 95% CI 1.03 to 1.43, I2 = 59%). We judged the GRADE quality of evidence to be low, downgraded due to inconsistency in addition to risk of bias. There was also low quality evidence of benefit of a group programme compared to no-intervention controls, (9 trials, N = 1098, RR 2.60, 95% CI 1.80 to 3.76 I2 = 55%). We did not detect evidence that group therapy was more effective than a similar intensity of individual counselling (6 trials, N = 980, RR 0.99, 95% CI 0.76 to 1.28, I2 = 9%). Programmes which included components for increasing cognitive and behavioural skills were not shown to be more effective than same-length or shorter programmes without these components. Group therapy is better for helping people stop smoking than self-help, and other less intensive interventions. There is not enough evidence to evaluate whether groups are more effective, or cost-effective, than intensive individual counselling. There is not enough evidence to support the use of particular psychological components in a programme beyond the support and skills training normally included. | We identified 66 trials comparing group-based programmes to other types of support, or comparing different types of group programme. The most recent search was in May 2016. In 13 trials (4395 participants) people in the control conditions were provided with a self-help programme. There was a benefit for the group-based approach, with the chance of quitting increased by 50% to 130%. This means that if five in 100 people were able to quit for at least six months using self-help materials, eight to 12 in 100 might be successful if offered group support. We judged the quality of this evidence as moderate, because studies did not report methods in enough detail to exclude possible bias. There was also evidence of a benefit of group support compared to advice and brief support from a healthcare professional (14 trials, 7286 participants), although the difference was smaller and more variable. We rated this as low-quality evidence, because of the variability as well as possible risk of bias. There was also low-quality evidence of a benefit in studies that did not provide the control group with any help to quit (9 trials, 1098 participants). Six trials (980 participants) compared group format with individual face-to-face counselling; there was no sign that one approach was more helpful than the other. The remaining studies compared different types of group programmes; typically they did not show differences, so it is not possible to show which components of group-based programmes are most helpful. |
We identified nine eligible trials that randomised 4940 participants, who had received surgical resection or curative radiotherapy, to either an immunotherapy group or a control group. Included immunological interventions were active immunotherapy (i.e. Bacillus Calmette-Guérin (BCG)), adoptive cell transfer (i.e. transfer factor (TF), tumour-infiltrating lymphocytes (TIL), dendritic cell-cytokine induced killer (DC-CIK), and antigen-specific cancer vaccines (melanoma-associated antigen 3 (MAGE-A3) and L-BLP25). Except for one small trial, which provided insufficient information for risk assessment, we assessed five studies at high risk of bias for at least one of the seven biases studied; we considered the risk of bias in the other three trials to be low. We included data from seven of the nine trials in the meta-analyses (4695 participants). We pooled data from 3693 participants from the three high quality RCTs to evaluate overall survival (OS) and progression-free survival (PFS). We found a small, but not statistically significant, improvement in OS (HR 0.94, 95% CI 0.83 to 1.06; P = 0.35), and PFS (HR 0.93, 95% CI 0.81 to 1.07; P = 0.19; high-quality evidence). The addition of immunotherapy resulted in a small, but not statistically significant, increased risk of having any adverse event (RR 1.15, 95% CI 0.97 to 1.37; P = 0.11, three trials, 3955 evaluated participants, moderate-quality evidence), or severe adverse events (RR 1.10, 95% CI 0.88 to 1.39; four trials, 4362 evaluated participants; low-quality evidence). We analysed data from six studies for one-, two-, and three-year survival rates (4265 participants), and from six studies for five-year survival rates (4234 participants). We observed no clear between-group differences (low-quality evidence for one- and two-year survival rates, and moderate-quality evidence for three- and five-year survival rate). No trial reported the overall response rates; only one trial provided health-related quality of life results. The current literature does not provide evidence that suggests a survival benefit from adding immunotherapy (excluding checkpoint inhibitors) to conventional curative surgery or radiotherapy, for patients with localised NSCLC (stages I to III). The addition of vaccine-based immunotherapy might increase the risk of adverse events. Several ongoing trials with immune checkpoints inhibitors (PD-1/PD-L1) might bring new insights for role of immunotherapy for patients with stages I to III NSCLC. | We searched four computerised databases and five trial registers to 20 January 2017. We looked for all trials that randomly allocated participants to one treatment or another (randomised controlled trials (RCTs)), and included adults (aged 18 years or older) with early non-small cell lung cancer (stages I to III), confirmed by laboratory testing of a sample of the tumour. We found nine RCTs, which included nearly 5000 participants who had received surgery or curative radiotherapy, and were randomly allocated to receive either immunotherapy or no further treatment. We found that giving immunotherapy, mainly vaccine-based (aiming to activate the host immune system to induce human immune response to tumour-specific antigens), after surgery or radiotherapy did not, on average, make people live longer. We did not find any results that could tell us whether the addition of immunotherapy improved the quality of life, but it seemed that those who were given vaccine-based immunotherapy may have experienced, on average, more side effects. At the moment, there is no evidence to support or refute giving immunotherapy (mainly vaccine-based) to people with localized NSCLC (stages I to III). RCTs are in progress that are testing new, more promising immunotherapy drugs (e.g. checkpoint inhibitors). The evidence we found about overall survival and progression-free survival was high quality. When we looked for evidence about how many patients lived to one, two, three, or five years, it was only moderate or low quality, because the RCTs were not very well done, and their results did not agree with each other. |
Eight studies were included, which represented 233 males with all severities of haemophilia A and B, ranging in age from eight years to 49 years. Study duration ranged from four to 12 weeks. Exercise interventions varied greatly and included resistance exercises, isometric exercises, bicycle ergometry, treadmill walking and hydrotherapy; therefore, comparison between studies was difficult. None of the studies measured or reported adverse effects from the interventions. None of the studies reported outcomes regarding bleed frequency, quality of life or aerobic activity. Overall risk of bias across all studies was assessed as unclear. Very few studies provided sufficient information for comparison. None of the studies reported data that favoured the control group. One study reported that six weeks of resistance training improved joint health status (Colorado score) compared to controls. The addition of pulsed electromagnetic fields also improved ankle scores compared to exercises alone, but this was not seen in the elbows or knees. Two studies reported statistically significant improvements in pain intensity after exercise interventions compared to controls. Hydrotherapy exercises produced significant decreases in pain compared to controls and land-based exercise groups. Two studies found improvement in joint motion in the exercise group compared to controls. One study compared land- and water-based exercises; there was no difference in the range of motion between the two groups; however, the water-based exercise group did show improvement over the control group. One study, comparing joint traction and proprioceptive neuromuscular facilitation for the elbow to a control group, showed no differences in biceps girth or strength after 12 weeks of intervention. Some studies reported comparisons between interventions. In one study, treadmill training significantly improved balance in children compared to bicycle ergometry. Another study added partial weight bearing exercises to quadriceps exercises and showed improved walking tolerance. Four studies evaluated quadriceps or hamstring strength (or both). The addition of bicycle ergometry and exercises with weights was more effective than static exercises and treadmill walking for strengthening knee flexors and extensors. Partial weight-bearing exercises through range were more effective than static and short arc exercises for improving knee extensor strength. The addition of treadmill walking to ultrasound, stretching and strengthening exercises showed increased peak torque of knee flexors and extensors and decrease in knee effusion. The results should be interpreted with caution due to the quality of evidence (GRADE) as outlined in the summary of findings tables, which demonstrates that all but one of the outcomes assessed were rated as low or very low due to the small sample sizes and potential bias. These results must be considered with caution. There is a lack of confidence in the results due to the small number of included studies and the inability to pool the results due to the heterogeneity of outcome measures. Most exercise interventions produced improvement in one or more of the measured outcomes including pain, range of motion, strength and walking tolerance. Hydrotherapy may be more effective than land exercises for pain relief in adults. Functional exercises such as treadmill walking and partial weight bearing exercises seem to be more effective than static or short arc exercises for improving muscle strength. These findings are consistent with the many non-controlled intervention reports in the haemophilia literature. No adverse effects were reported as a result of any of the interventions. However, some groups used prophylactic factor prior to exercise and other groups studied only subjects with moderate haemophilia. Therefore, the safety of these techniques for persons with severe haemophilia remains unclear. | We included eight studies with 233 male participants with haemophilia A or B (of any severity), aged eight to 49 years. Length of study ranged from four to 12 weeks. Several types of exercise programs were studied, including stretching, strengthening with weights, exercise in water, treadmill walking, and exercise bicycle. Some studies compared participants who did one type of exercise with those who did another type of exercise; other studies compared an exercise group with a control group that did no exercise. There were no data relating to our primary outcomes which indicated whether bleed frequency changed after an exercise program. There were no adverse effects measured or reported. Quality of life was not measured. Regarding our secondary outcomes, improvements were seen in balance, joint health, and pain. Walking distance was the only functional status measured. In an unplanned additional analysis, improvements were seen in the range of motion, biceps perimeter; strength, and knee circumference. These small studies showed more improvements in pain, muscle strength and joint range of motion in exercise groups than in control groups. Studies that included functional activity, such as walking on a treadmill, showed more improvement than exercise alone. Exercise in water seems to be more effective than land exercise in relieving joint pain in adults. Four studies included only males with moderate haemophilia. Three studies included all severities of haemophilia and in one, participants used clotting factor prior to participating. Two studies included males with both haemophilia A and B; three studies did not specify type. Only one study limited their participants to those with severe haemophilia, and these also had osteoporosis. It is not clear whether the same results would be achieved if only males with severe haemophilia A were studied. The results should be interpreted with caution due to the quality of the evidence; we judged that all but one of the outcomes assessed were low or very low quality, due to small sample sizes and potential bias. |
Two studies involving a total of 467 participants, aged over 18 years, were eligible for inclusion. Both studies assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal epilepsy. We assessed one study as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results showed that participants taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76, 95% CI 1.14 to 2.72; 2 studies, 467 participants; moderate-quality evidence), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16, 95% CI 1.28 to 3.67; 2 studies, 467 participants; moderate-quality evidence). For the tolerability outcomes, results indicated that the proportion of participants who experienced adverse events in the losigamone group was higher than in the placebo group (RR 1.34, 95% CI 1.00 to 1.80; 2 studies, 467 participants; moderate-quality evidence). Dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82, 99% CI 1.69 to 8.64; 2 studies; 467 participants; moderate-quality evidence). Neither study reported the proportion of participants achieving seizure freedom. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events. The results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy. However, the included studies were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled studies with a longer-term duration are needed. We did not find any new studies since the last version of this review. We judged the overall quality of the evidence for the outcomes assessed as moderate. | The evidence is current to August 2019. We found two studies assessing add-on losigamone for focal epilepsy, which recruited a total of 467 participants aged over 18 years. Both studies assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal epilepsy. The results of this review showed that participants taking losigamone as an add-on treatment were more likely to reduce their seizure frequency by 50% or more in the short term; however losigamone was associated with more treatment withdrawal side effects than placebo. The most frequent adverse event caused by losigamone was dizziness. We assessed one study as being of good methodological quality while the other was of uncertain quality. We judged the overall quality of the evidence for the outcomes assessed as moderate. |
We included 16 trials with 3048 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was mean difference (MD) -1.43 mmHg (95% confidence interval (CI) -2.15 to -0.72) and -0.98 mmHg (95%CI -1.46 to -0.50) respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years (7 trials with 399 participants) was -2.11 mmHg (95%CI -3.58 to -0.64) / -2.61 mmHg (95% CI -3.74, -1.49). The effect on systolic and diastolic blood pressure for those 35 years or more (9 trials with 2649 participants) was -0.96 mmHg (95%CI -1.83 to -0.09) / -0.59 mmHg (95%CI -1.13 to -0.06). The effect on systolic and diastolic blood pressure for women (6 trials with 1823 participants) was -1.45 mmHg (95% CI -2.78 to -0.12) / -0.92 mmHg (95% CI -1.71 to -0.14). The effect on systolic and diastolic blood pressure for men (5 trials with 617 participants) was -2.07 (95%CI -3.56 to -0.59] / -1.91 (95%CI -2.80 to -1.02).The quality of evidence for each of these outcomes was high. The effect is consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was 0.08 mmHg (95% CI -2.16 to 2.32) with doses less than 1000 mg, -1.14 mmHg (95% CI -2.01 to -0.27) with 1000 - 1500 mg, and -2.79 mmHg (95% CI -4.71 to -0.86) with more than 1500 mg. The effect on diastolic blood pressure was -0.54 mmHg (95% CI -2.23 to 1.15), -0.71 mmHg (95% CI -1.37 to -0.06) and -1.43 mmHg (95% CI -2.22 to -0.64) respectively. The quality of evidence for each of these outcomes was high. None of the studies reported adverse events. An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. These results should be interpreted with caution, since the proposed biological mechanism explaining the relationship between calcium and blood pressure has not been fully confirmed. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake. | We selected studies that assessed the effect of dietary calcium interventions such as supplementation or food fortification on blood pressure in normotensive people of all ages. The last search date was October 2014. This review analysed information from 16 trials (3048 participants). We found that an increase in calcium intake slightly reduces both systolic and diastolic blood pressure 1.43 mmHg lower and 0.98 mmHg lower respectively. This effect was higher with doses of calcium above 1000 mg/day. Systolic blood pressure was reduced by 1.14 mmHg with doses of calcium 1000 to 1500 mg/day and by 2.79 mmHg with doses of calcium equal to or over 1500 mg/day. We noted a reduction in blood pressure in both men and women and at ages from 11 to 82 years old, but the reduction was greater among younger people. Systolic blood pressure was reduced by 2.11 mmHg among those less than 35 years and by 0.96 mmHg among those 35 years or older. None of the studies reported adverse events. We need further research to determine the ideal dosage of supplementation and whether it is more effective and safer as part of the diet or as a supplement. We found high quality of evidence for systolic and diastolic blood pressure in both men and women. The quality of evidence was also high for participants 35 years or older and moderate for younger people. The quality of evidence was high for doses of calcium of 1000 to 1500 mg/day and was moderate for lower or higher doses. Five of the 16 trials were industry funded. |
We included twelve trials (577 participants). Ten trials (531 participants) enrolled people with a diabetic foot ulcer: pooled data of five trials with 205 participants showed an increase in the rate of ulcer healing (risk ratio (RR) 2.35, 95% confidence interval (CI) 1.19 to 4.62; P = 0.01) with HBOT at six weeks but this benefit was not evident at longer-term follow-up at one year. There was no statistically significant difference in major amputation rate (pooled data of five trials with 312 participants, RR 0.36, 95% CI 0.11 to 1.18). One trial (16 participants) considered venous ulcers and reported data at six weeks (wound size reduction) and 18 weeks (wound size reduction and number of ulcers healed) and suggested a significant benefit of HBOT in terms of reduction in ulcer area only at six weeks (mean difference (MD) 33.00%, 95% CI 18.97 to 47.03, P < 0.00001). We identified one trial (30 participants) which enrolled patients with non-healing diabetic ulcers as well as venous ulcers ("mixed ulcers types") and patients were treated for 30 days. For this "mixed ulcers" there was a significant benefit of HBOT in terms of reduction in ulcer area at the end of treatment (30 days) (MD 61.88%, 95% CI 41.91 to 81.85, P < 0.00001). We did not identify any trials that considered arterial and pressure ulcers. In people with foot ulcers due to diabetes, HBOT significantly improved the ulcers healed in the short term but not the long term and the trials had various flaws in design and/or reporting that means we are not confident in the results. More trials are needed to properly evaluate HBOT in people with chronic wounds; these trials must be adequately powered and designed to minimise all kinds of bias. | We included twelve randomised trials (577 participants) in this updated review. Most of the included trials studied foot ulcers in people with diabetes (10 trials). For diabetes-related foot ulcers, we found that HBOT seemed to improve the chance of healing in the short term (up to six weeks), but not with longer term follow-up. HBOT may reduce the number of major amputations in people with diabetes who have chronic foot ulcers. For chronic wounds caused by disease to the veins of the leg, we found that HBOT may reduce the size of wounds. For chronic wounds caused by lack of blood supply through the arteries or chronic pressure ulcers, we found no evidence to confirm or refute any effects of HBOT. We could not assess safety as none of the trials included in our review reported whether there were any major adverse events. This plain language summary is up-to-date as of 23/1/15 |
We included 33 trials with 5710 participants total; 29 were published from 2010 to 2015. Studies examined lidocaine, misoprostol, NSAIDs, and other interventions. Here we synthesize results from trials with sufficient outcome data and moderate- or high-quality evidence. For lidocaine, meta-analysis showed topical 2% gel had no effect on pain at tenaculum placement (two trials) or on pain during IUC insertion (three trials). Other formulations were effective compared with placebo in individual trials. Mean score for IUC-insertion pain was lower with lidocaine and prilocaine cream (MD -1.96, 95% CI -3.00 to -0.92). Among nulliparous women, topical 4% formulation showed lower scores for IUC-insertion pain assessed within 10 minutes (MD -15.90, 95% CI -22.77 to -9.03) and at 30 minutes later (MD -11.10, 95% CI -19.05 to -3.15). Among parous women, IUC-insertion pain was lower with 10% spray (median 1.00 versus 3.00). Compared with no intervention, pain at tenaculum placement was lower with 1% paracervical block (median 12 versus 28). For misoprostol, meta-analysis showed a higher mean score for IUC insertion compared with placebo (SMD 0.27, 95% CI 0.07 to 0.46; four studies). In meta-analysis, cramping was more likely with misoprostol (OR 2.64, 95% CI 1.46 to 4.76; four studies). A trial with nulliparous women found a higher score for IUC-insertion pain with misoprostol (median 46 versus 34). Pain before leaving the clinic was higher for misoprostol in two trials with nulliparous women (MD 7.60, 95% CI 6.48 to 8.72; medians 35.5 versus 20.5). In one trial with nulliparous women, moderate or severe pain at IUC insertion was less likely with misoprostol (OR 0.30, 95% CI 0.16 to 0.55). In the same trial, the misoprostol group was more likely to rate the experience favorably. Within two trials of misoprostol plus diclofenac, shivering, headache, or abdominal pain were more likely with misoprostol. Participants had no vaginal delivery. One trial showed the misoprostol group less likely to choose or recommend the treatment. Among multiparous women, mean score for IUC-insertion pain was lower for tramadol 50 mg versus naproxen 550 mg (MD -0.63, 95% CI -0.94 to -0.32) and for naproxen versus placebo (MD -1.94, 95% CI -2.35 to -1.53). The naproxen group was less likely than the placebo group to report the insertion experience as unpleasant and not want the medication in the future. An older trial showed repeated doses of naproxen 300 mg led to lower pain scores at one hour (MD -1.04, 95% CI -1.67 to -0.41) and two hours (MD -0.98, 95% CI -1.64 to -0.32) after insertion. Most women were nulliparous and also had lidocaine paracervical block. Nearly all trials used modern IUC. Most effectiveness evidence was of moderate quality, having come from single trials. Lidocaine 2% gel, misoprostol, and most NSAIDs did not help reduce pain. Some lidocaine formulations, tramadol, and naproxen had some effect on reducing IUC insertion-related pain in specific groups. The ineffective interventions do not need further research. | We reviewed randomized trials of reducing pain during IUC insertion through 22 June 2015. We found 33 studies with a total of 5710 women. Most were recent trials. Methods tested were nonsteroidal anti-inflammatory drugs (NSAIDs), lidocaine, misoprostol, and other treatments. Lidocaine 2% gel had no effect on pain during IUC insertion (three trials) or pain with tenaculum (type of forceps) placement (two trials). Other types of lidocaine showed some effect. Pain score for IUC insertion was lower with a lidocaine and prilocaine cream and with 10% lidocaine spray. With 4% lidocaine gel, pain scores were lower shortly after IUC insertion. With 1% lidocaine injection, pain score at tenaculum placement was lower compared with no intervention. With four misoprostol trials, the pain score with IUC insertion was higher for misoprostol versus placebo ('dummy' treatment). Two other trials showed higher pain scores with misoprostol versus placebo either at IUC insertion or after. However, another study showed the misoprostol group had less serious IUC-insertion pain. Also, the misoprostol group rated the insertion more favorably. In analysis of four trials, cramping was more likely with misoprostol versus placebo. Within two other trials, the misoprostol group was more likely to have shivering, headache, or abdominal pain. In one study, the misoprostol group was less likely to choose the treatment again or recommend it. Pain score during IUC insertion was lower for the opioid tramadol versus naproxen. In the same trial, pain was lower for naproxen versus placebo. The naproxen group was less likely than the placebo group to rate the experience as unpleasant and not want the treatment in the future. In another trial, women with several naproxen doses had lower pain scores after IUC insertion than the placebo group. Overall, the effectiveness results were of moderate quality, having come from single studies. Trials of lidocaine, tramadol and naproxen showed some effect on reducing pain from IUC insertion. |
Seventeen studies were included in the review, involving 3097 participants. Based on all 17 studies, SSRIs as a group were more effective than placebo in reducing the symptoms of OCD between 6 and 13 weeks post-treatment, measured using the Yale-Brown Obsessive Compulsive Scale (YBOCS) (WMD -3.21, 95% CI -3.84 to -2.57). The WMD for individual SSRI drugs were similar and not statistically different. Based on 13 studies (2697 participants), SSRIs were more effective than placebo in achieving clinical response at post-treatment (RR 1.84, 95% CI 1.56 to 2.17). The pooled RR was shown to be similar between individual SSRI drugs. Although reported adverse effects data were more limited, with few exceptions, the overall and individual adverse effects for the different SSRIs were always worse than for placebo and, in the majority of cases, the difference was statistically significant. Nausea, headache and insomnia were always reported amongst the most common adverse effects in trials of each of the drugs. SSRIs are more effective than placebo for OCD, at least in the short-term, although there are differences between the adverse effects of individual SSRI drugs. The longer term efficacy and tolerability of different SSRI drugs for OCD has yet to be established. | Individual randomised controlled trials have demonstrated that antidepressants are effective for OCD. This review summarises all the available evidence for one class of antidepressant drugs, the selective serotonin re-uptake inhibitors (SSRIs) (including citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) compared to placebo in the treatment of OCD in adults. The review included 17 studies (3097 participants), and showed that SSRIs were effective in reducing the symptoms of OCD. Based on 13 studies (2697 participants), the review showed that people receiving SSRIs were nearly twice as likely as those receiving placebo to achieve clinical response (defined as a 25% or more reduction in symptoms). Indirect comparisons of effectiveness suggested that although individual SSRI drugs were similar in their effectiveness, they differed in terms of their adverse effects. The most common adverse effect reported by participants was nausea. Further studies involving head to head comparisons between different SSRI drugs are required to obtain more reliable information on differences between SSRIs, both in terms of effectiveness and adverse effects. |
We included five RCTs involving 576 people. The trials were largely at low risk of bias, but we considered the quality of the evidence from these trials as moderate to low, largely due to imprecision from small sample sizes. Two out of the five trials reported on improvement in nerve function at one year. These two trials compared prednisolone with placebo. One trial, with 84 participants, treated mild sensory impairment of less than six months' duration, and the other, with 95 participants, treated nerve function impairment of 6 to 24 months' duration. There was no significant difference in nerve function improvement after 12 months between people treated with prednisolone and those treated with placebo. Adverse events were not reported significantly more often with corticosteroids than with placebo. The other three trials did not report on the primary outcome measure. One (334 participants) compared three corticosteroid regimens for severe type 1 reactions. No serious side effects of steroids were reported in any participant during the follow-up period. Another trial (21 participants) compared low-dose prednisone with high-dose prednisone for ulnar neuropathy. Two participants on the higher dose of prednisone reported adverse effects. The last (42 participants) compared intravenous methylprednisolone and oral prednisolone with intravenous normal saline and oral prednisolone. The trial found no significant differences between the groups in the occurrence of adverse events. Corticosteroids are used for treating acute nerve damage in leprosy, but moderate-quality evidence from two RCTs treating either longstanding or mild nerve function impairment did not show corticosteroids to have a superior effect to placebo on nerve function improvement. A third trial showed significant benefit from a five-month steroid regimen over a three-month regimen in terms of response to treatment (need for additional corticosteroids). Further RCTs are needed to establish optimal corticosteroid regimens and to examine the efficacy and safety of adjuvant or new therapies for treating nerve damage in leprosy. Future trials should address non-clinical aspects, such as costs and impact on quality of life, which are highly relevant indicators for both policymakers and participants. | We conducted a wide search for reports of clinical trials of treatments for nerve damage in leprosy. We found five clinical trials that met our criteria, involving 576 people with leprosy. Two of the included trials compared prednisolone with placebo. One of these trials, with 84 participants, recruited people who had mild abnormality of feeling of less than six months' duration and the other, with 95 participants, assessed treatment effects in people with abnormal nerve function of 6 to 24 months' duration. A third trial, with 334 participants, compared three 12-month corticosteroid regimens for severe type 1 reactions. Type 1 reactions are episodes in which nerves become inflamed. The fourth trial (21 participants) compared a low dose of prednisone with a high dose of prednisone for people with damage to the ulnar nerve (a nerve in the arm). The fifth trial (42 participants) compared intravenous methylprednisolone and oral prednisolone with intravenous normal saline and oral prednisolone in people with a type 1 leprosy reaction or abnormal nerve function of no more than six months' duration. There was no important difference in improvement in nerve function between people treated with prednisolone or with placebo after one year, according to two trials. More people on a three-month course of prednisolone failed to respond to treatment and required extra corticosteroids compared to people on either a high-dose or a low-dose regimen of five months' duration. The trials comparing corticosteroids with placebo and a trial comparing intravenous methylprednisolone and oral prednisolone with intravenous normal saline and oral prednisolone found no differences in the occurrence of adverse events between groups. We considered the quality of the evidence to be moderate to low. Although trials were well conducted and designed, they were largely small and did not always use proven measures to capture the effects of corticosteroids. The evidence in this review is up to date to June 2015. |
We included one RCT, involving 48 women who had a miscarriage between eight to 24 weeks of gestation. Of the 19 women in the treatment group, 14 had therapeutic dilatation & curettage (D&C) and five had spontaneous miscarriage; of the 29 women in the control group, 25 had therapeutic D&C and four had spontaneous miscarriage. The treatment group received 300 µg anti-D Ig intramuscular injection and were compared with a control group who received 1 cc homogenous gamma globulin placebo. This review's primary outcomes (development of a positive Kleihauer Betke test (a test that detects fetal cells in the maternal blood; and development of RhD alloimmunisation in a subsequent pregnancy) were not reported in the included study. Similarly, none of the review's secondary outcomes were reported in the included study: the need for increased surveillance for suspected fetal blood sampling and fetal transfusions in subsequent pregnancies, neonatal morbidity such as neonatal anaemia, jaundice, bilirubin encephalopathy, erythroblastosis, prematurity, hypoglycaemia (low blood sugar) in subsequent pregnancies, maternal adverse events of anti-D administration including anaphylactic reaction and blood-borne infections. The included study did report subsequent Rh-positive pregnancies in three women in the treatment group and six women in the control group. However, due to the small sample size, the study failed to show any difference in maternal sensitisation or development of Rh alloimmunisation in the subsequent pregnancies. There are insufficient data available to evaluate the practice of anti-D administration in an unsensitised Rh-negative mother after spontaneous miscarriage. Thus, until high-quality evidence becomes available, the practice of anti-D Immunoglobulin prophylaxis after spontaneous miscarriage for preventing Rh alloimmunisation cannot be generalised and should be based on the standard practice guidelines of each country. | Other Cochrane reviews provide clear evidence that giving anti-D immunoglobulin (anti-D) within 72 hours of the birth to a Rh-negative mother of a Rh-positive baby and during the third trimester reduces Rh antibody formation in future pregnancies. The chances of developing Rh antibodies may also be reduced if anti-D is given to Rh-negative women following a spontaneous miscarriage or a dilatation & curettage (D&C) for incomplete miscarriage after 12 weeks. However, our review only identified one poor quality randomised controlled trial (involving 48 women) that considered anti-D administration after therapeutic D&C or spontaneous miscarriage for preventing Rh alloimmunisation (development of antibodies in response to antigens from a non-self protein). The included study did not report any data on the review's primary or secondary outcomes. More high-quality research is needed in this field. |
Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I2 = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I2=29%), moderate quality evidence). SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question. Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I2 = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related. The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses. SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent. | The review included 31 randomised controlled trials which compared SSRIs with placebo in a total of 4372 women who were clinically diagnosed with PMS. SSRIs were found to be effective for reducing the overall symptoms of PMS and also for reducing specific types of symptoms (psychological, physical and functional symptoms, and irritability). SSRIs were usually taken for about two weeks before the start of the menstrual period (the luteal phase) or every day (continuously). Both regimens appeared to be equally effective, although more research is needed to confirm this. Adverse effects were more common in the women taking SSRIs than in those taking placebo. The most commonly occurring side effects were nausea and decreased energy. The review authors calculated that nausea is likely to occur as a drug side effect in approximately one out of seven women with PMS taking a moderate dose of SSRIs, and lack of energy is likely to occur as a drug side effect in approximately one out of every nine women. The overall quality of the evidence was rated as low to moderate, the main weakness being poor reporting of methods in the included studies. At least 21 of the studies received funding from pharmaceutical companies. |
No eligible published trials were identified. We identified a completed randomised controlled trial that was designed to evaluate the effects of a diet and exercise intervention compared with standard care in women with a history of GDM, however to date, it has only published results on women who were pregnant at randomisation (and not women in the interconception period). We also identified an ongoing trial, in obese women with a history of GDM planning a subsequent pregnancy, which is assessing the effects of an intensive lifestyle intervention, supported with liraglutide treatment, compared with usual care. We also identified a trial that was designed to evaluate the effects of a weight loss and exercise intervention compared with lifestyle education also in obese women with a history of GDM planning a subsequent pregnancy, however it has not yet been published. These trials will be re-considered for inclusion in the next review update. The role of interconception care for women with a history of GDM remains unclear. Randomised controlled trials are required evaluating different forms and protocols of interconception care for these women on perinatal and long-term maternal and infant health outcomes, acceptability of such interventions and cost-effectiveness. | We searched for trials which looked at the health outcomes for women and babies after specific interconception care, and compared the outcomes for standard care (with no interconception care of this type). Our search identified one trial which has yet to issue a full set of results, plus two further trials; one of these is still underway and the other has yet to be published. Because there are no studies currently available, there is not enough evidence at present to say if interconception care for women with a history of GDM can help to improve the health of mothers and their infants. More high-quality studies are needed, which assess both short- and long-term health outcomes for women and their babies, as well as evaluating the impact on the health services. |
In the 2014 update of the review, 15 trials have been included, with a total of 453 participants across seven comparison groups. The included trials had either a low or unclear risk of bias for most of the parameters used for risk assessment. Only short-term outcomes could be assessed due to the short duration of follow up in the included trials. None of the primary outcomes, (incidence of ischaemic heart disease, number of deaths and age at death) were evaluated in any of the included trials. No significant differences were noted for the majority of secondary outcomes for any of the planned comparisons. However, a significant difference was found for the following comparisons and outcomes: for the comparison between plant sterols and cholesterol-lowering diet (in favour of plant sterols), total cholesterol levels, mean difference 0.30 mmol/l (95% confidence interval 0.12 to 0.48); decreased serum LDL cholesterol, mean difference -0.60 mmol/l (95% CI -0.89 to -0.31). Fasting serum HDL cholesterol levels were elevated, mean difference -0.04 mmol/l (95% CI -0.11 to 0.03) and serum triglyceride concentration was reduced, mean difference -0.03 mmol/l (95% CI -0.15 to -0.09), although these changes were not statistically significant. Similarly, guar gum when given as an add on therapy to bezafibrate reduced total cholesterol and LDL levels as compared to bezafibrate alone. No conclusions can be made about the effectiveness of a cholesterol-lowering diet, or any of the other dietary interventions suggested for familial hypercholesterolaemia, for the primary outcomes: evidence and incidence of ischaemic heart disease, number of deaths and age at death,due to the lack of data on these. Large, parallel, randomised controlled trials are needed to investigate the effectiveness of a cholesterol-lowering diet and the addition of omega-3 fatty acids, plant sterols or stanols, soya protein, dietary fibers to a cholesterol-lowering diet. | This review aimed to compare cholesterol-lowering dietary interventions either in combination with each other or alone. These interventions included adding omega-3 fatty acids or plant sterols or plant stanols or soya proteins to diet. Fifteen trials were included in this updated review. The included trials had either a low or unclear risk of bias for most of the domains used for risk assessment. All the trials were short term and the majority were cross-over in design. For most of the comparisons there was no significant difference in the various intervention strategies when compared to cholesterol-lowering diet. However, for total cholesterol levels, serum low density lipoprotein (LDL) concentrations, a significant benefit was obtained with plant sterols. However, before drawing any conclusions, methodological problems with pooling results from cross-over trials should be considered. There is a need for long-term trials with parallel group design to assess the potential benefits and harms of a cholesterol-lowering diet. |
Seventeen studies (1586 children) were included. All studies enrolled children at increased risk of AOM. In seven studies the children were prone to otitis media. The majority were high-quality studies and most (16 studies) reported data for our primary outcomes. One reported AOM with perforation or CSOM. Long-term antibiotics reduced any episode of AOM (14 studies, 1461 children, risk ratio (RR) 0.65, 95% CI 0.53 to 0.79; random-effects model) and number of episodes of AOM (13 studies, 1327 children, incidence rate ratio (IRR) 0.51, 95% CI 0.39 to 0.66; random-effects model). Approximately five children would need to be treated long-term to prevent one child experiencing AOM whilst on treatment. Antibiotics prevented 1.5 episodes of AOM for every 12 months of treatment per child. We explored statistical heterogeneity. Long-term antibiotics were not associated with a significant increase in adverse events (12 studies, 817 children, RR 1.99, 95% CI 0.25 to 15.89; random-effects model). For children at risk, antibiotics given once or twice daily will reduce the probability of AOM while the child is on treatment. In similar populations, antibiotics will reduce the number of episodes of AOM per year from around three to around 1.5. We believe that larger absolute benefits are likely in high-risk children. These conclusions were not affected by sensitivity analyses. | This review included 17 studies (1586 children). Long-term antibiotics (equal to or more than six weeks) almost halved the risk of further infections. There was not enough information to know if antibiotics reduced acute otitis media with perforation or chronic suppurative otitis media (chronic perforation), or improved long-term outcomes. Antibiotics did not appear to be a frequent cause of significant side effects (for example, allergic reactions or diarrhea). Parents must balance these potential side effects plus the cost and inconvenience associated with antibiotics against the likely benefits of treatment. Antibiotic resistance from the long-term use of these drugs is also an issue which should be considered, particularly for children with recurring infections. |
Twelve studies (4755 participants) compared intranasal sumatriptan with placebo or an active comparator. Most of the data were for the 10 mg and 20 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 10 mg versus placebo the NNTs were 7.3, 7.4, and 5.5 for pain-free at two hours, and headache relief at one and two hours, respectively. For sumatriptan 20 mg versus placebo the NNTs were 4.7, 4.9, and 3.5, respectively, for the same outcomes. The 20 mg dose was significantly better than the 10 mg dose for each of these three primary efficacy outcomes. Relief of headache-associated symptoms, including nausea, photophobia, and phonophobia, was greater with sumatriptan than with placebo, and use of rescue medication was lower with sumatriptan than placebo. For the most part, adverse events were transient and mild and were more common with sumatriptan than placebo. Direct comparison of sumatriptan with active treatments was limited to two studies, one comparing sumatriptan 20 mg and dihydroergotamine (DHE) 1 mg, and one comparing sumatriptan 20 mg with rizatriptan 10 mg. Intranasal sumatriptan is effective as an abortive treatment for acute migraine attacks, relieving pain, nausea, photophobia, phonophobia, and functional disability, but is associated with increased adverse events compared with placebo. | This review found that a single intranasal dose was effective in relieving migraine headache pain and associated symptoms of nausea, sensitivity to light, and sensitivity to sound. Pain was reduced from moderate or severe to no pain by two hours in approximately 2 in 10 people (24%) taking sumatriptan 10 mg, compared with about 1 in 10 (10%) taking placebo. Pain was reduced from moderate or severe to no worse than mild pain by two hours in 5 in 10 people (50%) taking sumatriptan 10 mg, compared with approximately 3 in 10 (32%) taking placebo. In addition to relieving headache pain, sumatriptan also relieved symptoms of nausea and sensitivity to light and sound by two hours in about half of those who took it, compared with about one-third of those who took placebo. The 20 mg dose had greater efficacy, but may be associated with more adverse events, most of which were of short duration and mild or moderate in severity. |
Nine trials comparing either agalsidase alfa or beta in 351 participants fulfilled the selection criteria. Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores measured by the Brief Pain Inventory severity, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval -3.79 to -0.41; at up to five months, mean difference -1.90 (95% confidence interval -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% confidence interval -3.66 to -0.34). There was a significant difference in the Brief Pain Inventory pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% confidence interval -3.92 to -0.28) but not at other time points. Death was not an outcome in either of the trials. One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% confidence interval -2.09 to -1.31); heart, mean difference -0.90 (95% confidence interval -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% confidence interval -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain. Only two trials compared agalsidase alfa to agalsidase beta. One of them showed no significant difference between the groups regarding adverse events, risk ratio 0.36 (95% confidence interval 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; (95% confidence interval 0.03 to 2.57). Two trials compared different dosing schedules of agalsidase alfa. One of them involved three different doses (0.2 mg/kg every two weeks; 0.1 mg/kg weekly and; 0.2 mg/kg weekly), the other trial evaluated two further doses to the dosage schedules: 0.4 mg/kg every week and every other week. Both trials failed to show significant differences with various dosing schedules on globotriaosylceramide levels. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. One trial comparing agalsidase alfa to agalsidase beta showed no significant difference for any adverse events such as dyspnoea and hypertension. The methodological quality of the included trials was generally unclear for the random sequence generation and allocation concealment. Trials comparing enzyme replacement therapy to placebo show significant improvement with enzyme replacement therapy in regard to microvascular endothelial deposits of globotriaosylceramide and in pain-related quality of life. There is, however, no evidence identifying if the alfa or beta form is superior or the optimal dose or frequency of enzyme replacement therapy. With regards to safety, adverse events (i.e., rigors, fever) were more significant in the agalsidase beta as compared to placebo. The long-term influence of enzyme replacement therapy on risk of morbidity and mortality related to Anderson-Fabry disease remains to be established. This review highlights the need for continued research into the use of enzyme replacement therapy for Anderson-Fabry disease. | Nine studies enrolled 351 participants. The studies used different formulations of the enzyme, Agalsidase alfa or beta, and compared them to placebo (a 'dummy' treatment) or to each other. Comparison was also made in regard to different dosing schedules. Two studies comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma. The combined effects were not significant between the treatment and placebo groups. The study that reported pain and pain-related quality of life showed an improvement for participants receiving treatment over the six-month observation period. Death was not an outcome in either study. One of the three studies comparing agalsidase beta to placebo reported on globotriaosylceramide and showed improvement in kidney, heart and composite results. There was no significant difference for death and no studies reported on pain. Only two studies compared agalsidase alfa to agalsidase beta. One of them showed no significant difference for any adverse events such as dyspnoea, hypertension and gastrointestinal symptoms - these are not adverse events as gastrointestinal problems are actually a symptom, as may be hypertension in the context of renal disease. Two studies compared different dosing schedules of agalsidase alfa. No differences were found among the schedules for self-assessed health state or for pain scores. In summary, studies comparing enzyme replacement therapy to placebo show significant results in regard to microvascular endothelial deposits of globotriaosylceramide and in pain-related quality of life. There is, however, no evidence identifying if the alfa or beta form is superior, though included trials were small in sample size. With regards to safety, adverse events (i.e., rigors, fever) were more significant with agalsidase beta as compared to placebo. From the information available in most of the study reports, we were not able to clearly judge whether all volunteers had equal chances of being in either of the treatment groups and whether they would have known in advance or during the study which treatment they were receiving. |
Twenty studies with 1969 women were included in this review. These studies compared GnRHa, danazol and progestogens versus placebo or no treatment; GnRHa versus danazol, progestogens, GnRH antagonists or dilatation & curettage; and danazol versus progestogens. Four studies performed more than one comparison. When compared with no treatment, GnRHa used before hysteroscopic resection were associated with a higher rate of postoperative amenorrhoea at 12 months (RR 1.6, 95% CI 1.2 to 2.0, 7 RCTs, 605 women, moderate heterogeneity; I2 = 40%) and at 24 months (RR 1.62, 95% CI 1.04 to 2.52, 2 RCTs, 357 women, no heterogeneity; I2 = 0%), a slightly shorter duration of surgery (-3.5 minutes, 95% CI -4.7 to -2.3, 5 RCTs, 156 women, substantial heterogeneity; I2 = 72%) and greater ease of surgery (RR 0.32, 95% CI 0.22 to 0.46, 2 RCTs, 415 women, low heterogeneity; I2 = 4%). Postoperative dysmenorrhoea was reduced (RR 0.59, 95% CI 0.40 to 0.87, 2 RCTs, 133 women, no heterogeneity; I2 = 0%). The use of GnRHa had no effect on intraoperative complication rates (RR 1.47, 95% CI 0.35 to 6.06, 5 RCTs, 592 women, no heterogeneity; I2 = 0%), and participant satisfaction with this surgery was high irrespective of the use of pre-operative endometrial thinning agents (RR 0.99, 95% CI 0.93 to 1.05, 6 RCTs, 599 women, low heterogeneity; I2 = 11%). GnRHa produced more consistent endometrial atrophy than was produced by danazol (RR 1.84, 95% CI 1.23 to 2.75, 2 RCTs, 142 women, no heterogeneity; I2 = 0%). For other intraoperative and postoperative outcomes, any differences were minimal, and no benefits of GnRHa pretreatment were noted in studies in which women underwent second-generation ablation techniques. Both GnRHa and danazol produced side effects in a significant proportion of women, although few studies reported these in detail. Few randomised data were available to allow assessment of the effectiveness of progestogens as endometrial thinning agents. When reported, the long-term effects of endometrial thinning agents on benefits such as postoperative amenorrhoea were reduced with time. The main study weaknesses were that most participants received no follow-up beyond 24 months and that the studies used a small sample size. Heterogeneity for outcomes reported ranged from none to substantial. More than half the trials had no blinding of participants or outcome assessment. Most of the trials were determined to have uncertain selection and reporting bias, as they did not report allocation concealment and evidence of selective reporting was noted. The quality of reporting of adverse events was generally poor, but, when described in the studies, they included menopausal symptoms such as hot flushes, vaginal dryness, hirsutism, decreased libido and voice changes, as well as other side effects such as headache and weight gain. Low-quality evidence suggests that endometrial thinning with GnRHa and danazol before hysteroscopic surgery improves operating conditions and short-term postoperative outcomes. GnRHa produced slightly more consistent endometrial thinning than was produced by danazol, although both achieved satisfactory results. The effect of these agents on longer-term postoperative outcomes was reduced with time. No benefits of GnRHa pretreatment were apparent with second-generation ablation techniques. Also, side effects were more common when these agents were used. | The evidence is current to April 2013. The review included 20 randomised controlled trials with a total of 1969 premenopausal women with heavy menstrual bleeding for whom non-surgical treatment had not worked. Studies compared GnRH analogues, danazol and progestogens versus placebo or no treatment; GnRH analogues versus danazol, progestogens, GnRH antagonists or dilatation & curettage; and danazol versus progestogens. Four studies performed more than one comparison. Three studies used the newer second-generation surgical techniques for endometrial destruction. GnRH analogues and danazol used before hysteroscopic surgery improve both operating conditions for the surgeon and short-term bleeding symptoms for women (up to 24 months after surgery). GnRH analogues thin the lining of the womb better and more consistently than danazol, although both agents produce satisfactory results. Adverse effects were more common in women taking GnRH analogues or danazol compared with no treatment, and this was especially true with danazol. Adverse effects included menopausal symptoms such as hot flushes, vaginal dryness, hirsutism, decreased libido and voice changes, as well as other side effects such as headache and weight gain. The use of medications to thin the lining of the womb before surgery does not appear to improve heavy menstrual bleeding in the long term (i.e. longer than 24 months). However, only a few small studies followed up with women for longer than 24 months. Also, medications given to thin the womb lining do not provide additional benefit when used with the newer second-generation endometrial destruction techniques, which are being performed increasingly in hospitals. Overall, the quality of the evidence was very low because of risk of bias in the included studies and differences between the studies. The quality of reporting of adverse events was generally poor. |
We included four studies, all of which enrolled adults with frequent episodic TTH. They all specified using the IHS diagnostic criteria and reported mean baseline pain of at least moderate intensity. While 1253 people with TTH participated in these studies, the numbers available for any analysis were lower than this because outcomes were inconsistently reported and because many participants received active comparators. None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged one study to be at high risk of bias due to small size. Useful information was available only for ketoprofen 25 mg. For the IHS preferred outcome of being pain-free at two hours the NNT for ketoprofen 25 mg compared with placebo was 9.0 (95% confidence interval (CI) 4.8 to 72) in two studies (272 participants; low quality evidence). The NNT was 3.7 (95% CI 2.6 to 6.3) for pain-free or mild pain at two hours in two studies (272 participants; moderate quality evidence). Fewer people needed rescue medication with ketoprofen 25 mg than with placebo, with a number needed to treat to prevent one event (NNTp) of 6.2 (95% CI 4.3 to 11) in three studies (605 participants; moderate quality evidence). The number of participants reporting any adverse event was higher with ketoprofen 25 mg than placebo (NNH 15, (95% CI 8.7 to 45)) in three studies (651 participants with 66 events; low quality evidence). Most events were of mild to moderate intensity. Ketoprofen 25 mg was not different from paracetamol 1000 mg in two studies with 276 participants for any efficacy outcomes (low to moderate quality evidence); the RR for pain-free at two hours was 1.3 (95% CI 0.9 to 2.0). The number of participants reporting any adverse event was higher with ketoprofen 25 mg than with paracetamol (NNH 17, 95% CI 8.9 to 130)) in two studies (582 participants, 68 events; low quality evidence). Studies reported no serious adverse events. We judged the quality of the evidence comparing ketoprofen 25 mg with placebo or paracetamol 1000 mg as moderate to very low. Where evidence was downgraded it was because of the small number of studies and events. Ketoprofen 25 mg provided a small benefit compared with placebo in terms of being pain-free at two hours or having mild or no pain at two hours for people with frequent episodic TTH who have an acute headache of moderate or severe intensity. Its use was associated with more people experiencing adverse events. Ketoprofen 25 mg was not superior to paracetamol 1000 mg for any efficacy outcome. | In May 2016, we searched the medical literature and found four studies involving 1253 participants looking at ketoprofen for frequent episodic tension-type headache. Only a fraction of the participants were involved in comparisons between ketoprofen 25 mg and placebo (a dummy tablet). Results were usually reported two hours after taking the medicine or placebo. The International Headache Society recommends the outcome of being pain-free two hours after taking a medicine, but other outcomes are also suggested. Few studies reported these recommended outcomes, so there was limited information to analyse for some outcomes. The outcome of being pain-free at two hours was reported by 27 in 100 people taking ketoprofen 25 mg, and in 16 out of 100 people taking placebo, meaning that only 11 in 100 people benefited because of ketoprofen 25 mg (low quality evidence). The outcome of being pain-free or having only mild pain at two hours was reported by 66 in 100 people taking ketoprofen 25 mg, and in 38 out of 100 people taking placebo (moderate quality evidence), meaning that 28 in 100 people benefited because of ketoprofen 25 mg. About 14 in 100 people taking ketoprofen 25 mg reported having a side effect, which was slightly more than with placebo (7 in 100 people) (low quality evidence). Most side effects were mild or moderate in intensity. No side effects were serious. Ketoprofen 25 mg was not different from paracetamol 1000 mg for any measure of headache relief (moderate and low quality evidence), but was associated with more side events (low quality evidence). The quality of the evidence for being pain-free at two hours was low quality, and for having mild pain at two hours was moderate quality. Moderate quality evidence means that we are reasonably confident about the results. Low quality evidence means that we are not very certain about the results and they could change with more information. |
We identified seven RCTs. These trials differ in inclusion criteria, comparison with alternative treatment and outcomes. In a trial comparing IVIg with placebo, including 51 participants with myasthenia gravis worsening, the mean difference (MD) in quantitative myasthenia gravis score (QMGS) (MD 95% CI) after 14 days was: -1.60 (95% CI - 3.23 to 0.03) this result being borderline statistically significant in favour of IVIg. In an unblinded study of 87 participants with exacerbation comparing IVIg and plasma exchange there was no difference in myasthenic muscle score (MMS) after 15 days (MD -1.00; 95% CI -7.72 to 5.72). In a study of 84 participants with worsening myasthenia gravis there was no difference in change in QMGS 14 days after IVIg or plasma exchange (MD -1.50; 95% CI -3.43 to 0.43). In a study of 12 participants with moderate or severe myasthenia gravis, which was at high risk of bias from skewed allocation, the mean fall in QMGS both for IVIg and plasma exchange after four weeks was significant (P < 0.05). A study with 15 participants with mild or moderate myasthenia gravis found no difference in change in QMGS 42 days after IVIg or placebo (MD 1.60; 95% CI -1.92 to 5.12). A study included 33 participants with moderate exacerbations of myasthenia gravis and showed no difference in change in QMGS 14 days after IVIg or methylprednisolone (MD -0.42; 95% CI -1.20 to 0.36). All these three smaller studies were underpowered. The last trial, including 168 people with exacerbations, showed no evidence of superiority of IVIg 2 g/kg over IVIg 1 g/kg on the change of MMS after 15 days (MD 3.84; 95% CI -0.98 to 8.66). Adverse events due to IVIg were moderate (fever, nausea, headache), self-limiting and subjectively less severe than with plasma exchange (although, given the available data, no statistical comparison was possible). Other than where specific limitations are mentioned the trials were generally at low risk of bias. In exacerbation of myasthenia gravis, one RCT of IVIg versus placebo showed some evidence of the efficacy of IVIg and two did not show a significant difference between IVIg and plasma exchange. Another showed no significant difference in efficacy between 1 g/kg and 2 g/kg of IVIg. A further, but underpowered, trial showed no significant difference between IVIg and oral methylprednisolone. In chronic myasthenia gravis, there is insufficient evidence from RCTs to determine whether IVIg is efficacious. | Five of the RCTs evaluated the efficacy of IVIg for the treatment of exacerbations or worsening (the former being usually more severe than the latter). One RCT of IVIg versus placebo, which included 51 participants, showed some evidence of the efficacy of IVIg for treating myasthenia gravis with worsening weakness. Two trials, the first of which included the first 87 and the second 84 participants, showed no significant difference between IVIg and plasma exchange. In the first of these trials there was a high risk of bias because the assigned treatments were not hidden. A trial including 33 participants showed no difference in efficacy between IVIg and a corticosteroid (methylprednisolone) but did not recruit enough participants to detect an effect, so there is insufficient evidence to favour IVIg over corticosteroids in moderate exacerbations. Another trial, which included 168 participants, showed no evidence of superiority of IVIg 2 g/kg over IVIg 1 g/kg on the change of myasthenic muscle score (MMS) after 15 days (MD 3.84; 95% CI -0.98 to 8.66). Two RCTs evaluated the efficacy of IVIg for the treatment of moderate or severe myasthenia gravis. One compared, in 12 participants, IVIg and plasma exchange. The second, with 15 participants included, compared IVIg and a placebo. Both are underpowered and the first at some risk of bias, so no conclusion could be drawn from these two trials. There is no evidence from RCTs nor from other trials to determine whether IVIg improves function or reduces the need for steroids. |
Twelve studies with 13 comparisons were included. Four studies compared dietitian with doctor, seven with self-help resources, and only one study was found for dietitian versus nurse and dietitian versus counsellor comparisons. Participants receiving advice from dietitians experienced a greater reduction in blood cholesterol than those receiving advice only from doctors (-0.25 mmol/L (95% CI -0.37, -0.12 mmol/L)). There was no statistically significant difference in change in blood cholesterol between dietitians and self-help resources (-0.10 mmol/L (95% CI -0.22, 0.03 mmol/L)). No statistically significant differences were detected for secondary outcome measures between any of the comparisons with the exception of dietitian versus nurse for HDLc, where the dietitian group showed a greater reduction (-0.06 mmol/L (95% CI -0.11, -0.01)) and dietitian versus counsellor for body weight, where the dietitian group showed a greater reduction (-5.80 kg (95% CI -8.91, -2.69 kg)). Dietitians were better than doctors at lowering blood cholesterol in the short to medium term, but there was no evidence that they were better than self-help resources. There was no evidence that dietitians provided better outcomes than nurses. The results should be interpreted with caution as the studies were not of good quality and the analysis was based on a limited number of trials. | This review looked at the effectiveness of dietary advice given by dietitians to lower blood cholesterol, compared with the effectiveness of dietary advice given by other types of health professional or using self-help resources. The review found that advice by dietitians to lower blood cholesterol was more effective than that of doctors (in the short to medium term), but possibly not more effective than using self-help resources. There was no evidence to suggest that dietary advice given by dietitians was more effective than that given by nurses. |
We identified only one RCT (N = 200; mean follow up 68 months). This trial compared LDR-BT and RP. The risk of bias was deemed high. Primary outcomes (overall survival, cause-specific mortality, or metastatic-free survival) were not reported. Biochemical recurrence-free survival at 5 years follow up was not significantly different between LDR-BT (78/85 (91.8%)) and RP (81/89 (91.0%)); P = 0.875; relative risk 0.92 (95% CI: 0.35 to 2.42). For severe adverse events reported at 6 months follow up, results favored LDR-BT for urinary incontinence (LDR-BT 0/85 (0.0%) versus RP 16/89 (18.0%); P < 0.001; relative risk 0) and favored RP for urinary irritation (LDR-BT 68/85 (80.0%) versus RP 4/89 (4.5%); P < 0.001; relative risk 17.80, 95% CI 6.79 to 46.66). The occurrence of urinary stricture did not significantly differ between the treatment groups (LDR-BT 2/85 (2.4%) versus RP 6/89 (6.7%); P = 0.221; relative risk 0.35, 95% CI: 0.07 to 1.68). Long-term information was not available. We did not identify significant differences of mean scores between treatment groups for patient-reported outcomes function and bother as well as generic health-related quality of life. Low-dose rate brachytherapy did not reduce biochemical recurrence-free survival versus radical prostatectomy at 5 years. For short-term severe adverse events, low-dose rate brachytherapy was significantly more favorable for urinary incontinence, but radical prostatectomy was significantly more favorable for urinary irritation. Evidence is based on one RCT with high risk of bias. | We reviewed the published research on this treatment to investigate how effective and safe it is. Unfortunately, we identified only one randomized controlled trial comparing LDR-BT versus RP. The results were considerably prone to bias. Important survival outcomes were not reported. Due to lack of research studies, it has not been proven whether patients treated with this procedure live longer than patients treated with treatment alternatives. In this single study, after the intervention, a rise in prostate-specific antigen (PSA) was similarly likely to occur after LDR-BT and RP, but this finding does not resolve the question of whether cancer was truly present again in both groups. Urinary incontinence was less frequent after LDR-BT and urinary irritation was less frequent after RP at a short-term follow up at 6 months. No results were reported at 12 and 60 months. Significant differences after long-term follow up were not identified for patient-reported outcomes. At present, the question whether LDR-BT is a favorable treatment compared to other treatment alternatives in patients with localized prostate cancer remains unanswered. |
The review currently includes nine randomised controlled trials (RCTs) with 3361 participants. The overall rate of premature study discontinuation was very high (59.1%). Data for the comparisons of ziprasidone with amisulpride, clozapine, olanzapine, quetiapine and risperidone were available. Ziprasidone was a less acceptable treatment than olanzapine (leaving the studies early for any reason: 5 RCTs, n=1937, RR 1.26 CI 1.18 to 1.35, NNH 7 CI 5 to 10) and risperidone (3 RCTs, n=1029, RR 1.11 CI 1.02 to 1.20, NNH 14 CI 8 to 50), but not than the other second generation antipsychotic drugs. Ziprasidone was less efficacious than amisulpride (leaving the study early due to inefficacy: 1 RCT, n=123, RR 4.72 CI 1.06 to 20.98, NNH 8 CI 5 to 50) olanzapine (PANSS total score: 4 RCTs, n=1291, MD 8.32 CI 5.64 to 10.99) and risperidone (PANSS total score: 3 RCTs, n=1016, MD 3.91 CI 0.27 to 7.55). Based on limited data there were no significant differences in tolerability between ziprasidone and amisulpride or clozapine. Ziprasidone produced less weight gain than olanzapine (5 RCTs, n=1659, MD -3.82 CI -4.69 to -2.96), quetiapine (2 RCTs, n=754, RR 0.45 CI 0.28 to 0.74) or risperidone (3 RCTs, n=1063, RR 0.49 CI 0.33 to 0.74). It was associated with less cholesterol increase than olanzapine, quetiapine and risperidone. Conversely ziprasidone produced slightly more extrapyramidal side-effects than olanzapine (4 RCTs, n=1732, RR 1.43 CI 1.03 to 1.99, NNH not estimable) and more prolactin increase than quetiapine (2 RCTs, n=754, MD 4.77 CI 1.37 to 8.16), but less movement disorders (2 RCTs, n=822, RR 0.70 CI 0.51 to 0.97, NNT not estimable) and less prolactin increase (2 RCTs, n=767, MD -21.97 CI -27.34 to -16.60) than risperidone. Note: the 254 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed. Ziprasidone may be a slightly less efficacious antipsychotic drug than amisulpride, olanzapine and risperidone. Its main advantage is the low propensity to induce weight gain and associated adverse effects. However, the high overall rate of participants leaving the studies early limits the validity of any findings. | This review wanted to find out if there was evidence to support that there is any difference between ziprasidone and the other atypical medications. Because of the large number of people that dropped out of the studies it is difficult to draw any firm conclusions, however, people taking ziprasidone did not do as well regarding their symptoms, as those taking olanzapine and risperidone and perhaps amisulpride, but they were less likely to gain weight. |
We included four studies involving a total of 773 randomised participants aged between 14 months and 16 years. All four studies involved children with asthma, with the case-planning undertaken by a trained nurse educator. However, the discharge planning/education differed among the studies. We could include data from only two studies (361 children) in the meta-analysis. Two further studies enrolled children in both inpatient and outpatient settings, and one of these studies also included children with acute wheezing illness (no previous asthma diagnosis); the data specific to this review could not be obtained. For the primary outcome of exacerbations requiring hospitalisation, those in the intervention group were significantly less likely to be rehospitalised (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.16 to 0.50) compared to controls. This equates to 189 (95% CI 124 to 236) fewer admissions per 1000 children. No adverse events were reported in any study. In the context of substantial statistical heterogeneity between the two studies, there were no statistically significant effects on emergency department (OR 0.37, 95% CI 0.04 to 3.05) or general practitioner (OR 0.87, 95% CI 0.22 to 3.44) presentations. There were no data on cost-effectiveness, length of stay of subsequent hospitalisations, or adherence to medications. One study reported quality of life, with no significant differences observed between the intervention and control groups. We considered three of the studies to have an unclear risk of bias, primarily due to inadequate description of the blinding of participants and investigators. The fourth study was assessed as at high risk of bias as a single unblinded investigator was used. Using the GRADE system, we assessed the quality of the evidence as moderate for the outcome of hospitalisation and low for the outcomes of emergency department visits and general practitioner consultations. Current evidence suggests that individual caseworker-assigned discharge plans, as compared to non-caseworker-assigned plans, may be beneficial in preventing hospital readmissions for acute exacerbations in children with asthma. There was no clear indication that the intervention reduces emergency department and general practitioner attendances for asthma, and there is an absence of data for children with other chronic respiratory conditions. Given the potential benefit and cost savings to the healthcare sector and families if hospitalisations and outpatient attendances can be reduced, there is a need for further randomised controlled trials encompassing different chronic respiratory illnesses, ethnicity, socio-economic settings, and cost-effectiveness, as well as defining the essential components of a complex intervention. | We included all randomised controlled trials (a type of study in which participants are assigned to a treatment group using a random method) that assessed whether those who received individualised caseworker discharge planned management (the intervention group) had better outcomes compared to those who received usual care (the control group). We considered the number of hospital readmissions, emergency department visits, and/or unscheduled general practitioner visits following discharge. The evidence is current to 15 November 2017. We found four studies that included 773 children aged 14 months to 16 years. All the studies involved children with asthma. The programme used for the discharge plan differed among the studies, but all were delivered by a trained asthma educator (lay health worker or nurse specifically trained on educating patients with asthma). The studies followed the children for 2 to 14 months after discharge. We could only include data from two studies in a combined analysis (i.e. the meta-analysis), as the other two studies also enrolled children who were not hospitalised, and we could not obtain data specific to the children who were hospitalised and one of those studies included children with acute wheezing illness( no previous asthma diagnosis); the data specific to this review could not be obtained. In this review involving children hospitalised with asthma flare-ups, trained asthma educator-led and structured discharge plans that included follow-up support (compared to the control group) reduced the number of hospital readmissions for acute asthma. No clear benefit was seen on future emergency department or general practitioner visits for acute asthma. Data on cost-effectiveness, length of stay of future hospitalisations, and adherence to discharge medications were not available. One study reported quality of life and found no differences between the intervention and control group. There were no studies relating to other long-term breathing diseases. Individual caseworker-assigned discharge planned management, as compared to non-caseworker-assigned management, may prevent readmissions to hospital for asthma flare-ups in children. However, the current evidence is limited to only two studies in children with asthma. Further studies are needed in a broad range of long-term breathing diseases in childhood. We considered the quality of the evidence to be moderate for the outcome of hospital readmissions and low for the outcomes of future emergency department visits and general practitioner consultations for asthma flare-ups. |
Twenty-two out of 29 included studies (1793 women) contributed data to this review. The included studies did not report some our primary outcomes: maternal death, incidence of maternal postoperative wound infection, maternal postoperative other infection such as endometritis and urinary tract infection, neonatal death. Compared to women who had GA, women who had either epidural anaesthesia or spinal anaesthesia were found to have a significantly lower difference between pre and postoperative haematocrit. For epidural, the mean difference (MD) was 1.70% and 95% confidence interval (CI) 0.47 to 2.93 (one trial, 231 women) and for spinal anaesthesia, the MD was 3.10% and 95% CI 1.73 to 4.47 (one trial, 209 women). Compared with GA, women having either an epidural anaesthesia or spinal anaesthesia had a lower estimated maternal blood loss (epidural versus GA: standardised mean difference (SMD) -0.32 mL; 95% CI -0.56 to -0.07; two trials, 256 women; spinal versus GA anaesthesia: SMD -0.59 mL; 95% CI -0.83 to 0.35; two trials, 279 women). There was evidence of a significant difference in terms of satisfaction with anaesthetic technique - compared with the epidural or spinal group, more women in the GA group stated they would use the same technique again if they needed CS for a subsequent pregnancy (epidural versus GA: risk ratio (RR) 0.80; 95% CI 0.65 to 0.98; one trial, 223 women; spinal versus GA anaesthesia: RR 0.80; 95% CI 0.65 to 0.99; one trial, 221 women). No significant difference was seen in terms of neonatal Apgar scores of six or less and of four or less at five minutes and the need for neonatal resuscitation with oxygen. There is no evidence from this review to show that RA is superior to GA in terms of major maternal or neonatal outcomes. Further research to evaluate neonatal morbidity and maternal outcomes, such as satisfaction with technique, will be useful. | This review of trials sought to assess these benefits and harms. Twenty-two out of 29 included studies (1793 women) contributed data to this review. There were some differences that favoured regional anaesthesia, for example, less blood loss. The evidence on the differences in pain relief was difficult to evaluate. There were not enough participants to assess the very rare outcome of mortality for the mother, which may be an important aspect. None of the trials addressed important outcomes for women such as recovery times, effects on breastfeeding, effects on the mother-child relationship and length of time before mother feels well enough to care for her baby. As there is insufficient evidence on benefits and adverse effects, women are most likely to choose anaesthesia for caesarean section, depending on whether they wish to be awake or asleep for the birth. |
We included three studies involving 102 preterm or low birth weight infants in the review. The studies compared dilute (double-volume, half-strength) formula with full-strength (20 kcal/oz (˜ 68 to 70 kcal/100 mL)) formula. We assessed all three studies as having unclear risk of bias due to the likely absence of blinding of study personnel and the potential for selection bias in the largest trial. Data for the primary outcome of necrotising enterocolitis were not reported in any of the studies. We could combine two of the studies (88 infants) in the meta-analysis. The evidence suggests that dilute formula with double-volume (half-strength) may lead to fewer episodes of gastric residuals per day (one study; mean difference (MD) −1.20, 95% confidence interval (CI) −2.20 to −0.20; low-certainty evidence), fewer episodes of gastric residuals per baby until attaining 100 kcal/kg (one study; MD −0.80, 95% CI −1.32 to −0.28; low-certainty evidence), fewer episodes of vomiting per day (one study; MD −0.04, 95% CI −0.07 to −0.01; low-certainty evidence) and fewer occurrences of abdominal distension greater than 2 cm (two studies; MD −0.16, 95% CI −0.19 to −0.13; low-certainty evidence). For the secondary outcomes, data suggest that infants in the dilute formula with double-volume (half-strength) group may have attained an adequate energy intake earlier than infants in the full-strength group (two studies; MD −2.26, 95% CI −2.85 to −1.67; low-certainty evidence). There was no evidence of a difference between groups for weight gain one week after commencement of intragastric feeds (one study; MD 0.05 kg, 95% CI −0.06 to 0.15; low-certainty evidence). Data were not reported for length of hospital stay. There is low-certainty evidence from three small, old trials that use of dilute formula in preterm or low birth weight formula-fed infants may lead to an important reduction in the time taken for preterm infants to attain an adequate energy intake. However, our confidence in this result is limited due to uncertainty over risk of bias and sparsity of available data. Dilute formula may reduce incidence of feeding intolerance, but the clinical significance of the reduction is uncertain. The impact on serious gastrointestinal problems, including necrotising enterocolitis, was not reported in any of the trials. Further randomised trials are needed to confirm these results. | The evidence for this review is current as of 1 October 2018. We included three trials that compared dilute formula milk (half-strength, double-volume) with full-strength formula milk. The trials involved 102 preterm or low birth weight infants; two were conducted in the USA and one in India. The trials were small (14, 38 and 50 infants, respectively) and conducted between 25 and 30 years ago. The quality of two trials was judged to be poor due to insufficient information being provided in the trial publications, but judged to be moderate in the third trial (of 38 infants). None of the trials assessed necrotising enterocolitis as an outcome. Infants receiving dilute formula (half-strength, double-volume) experienced fewer episodes of feeding intolerance and achieved full energy intake earlier than infants receiving full-strength formula (20 kcal/oz (˜ 68 to 70 kcal/100 mL)). Feeding intolerance Two measures of feeding intolerance (abdominal distension and episodes of gastric residuals) were reported across the trials. Two trials (88 infants) provided data for abdominal distension and gastric residuals. Infants fed dilute formula experienced 19% (CI 16% to 23%) fewer episodes of abdominal distension (> 2 cm), equivalent to 0.67 episodes per infant in the half-strength group compared to 0.83 episodes in the full-strength group. It was not possible to combine data on gastric residuals but both trials reported fewer episodes of gastric residuals in the dilute formula group. The third trial (14 infants) only reported that there was no difference between the groups with respect to these two outcomes. Time to establish full enteral feeding In two trials (88 infants) infants receiving dilute formula experienced a 22% (CI 16% to 28%) reduction in the number of days required to reach an adequate energy intake (420 joules/kilogram), equivalent to 8 days in the half-strength group compared to 10.3 days in the full-strength group. In exclusively formula-fed preterm or low birth weight infants, low-certainty evidence shows that diluted formula may lead to an important reduction in the time taken to attain adequate enteral fluid and energy requirements, without increasing indicators of feeding intolerance. The clinical importance of the reduction in episodes of feeding intolerance is unclear. These findings are based on three small, old trials that may be of less relevance to current practice. A lack of data on other important outcomes, such as the incidence of necrotising enterocolitis and weight gain, limits the usefulness of the studies. |
We included seven RCTs (350 women analysed). The evidence was of very low to low quality: the main limitations being a low number of included women and surgery-related adverse events, substantial loss to follow-up and a large variety in outcome measures and timing of measurements. No studies reported ovarian cancer incidence after hysterectomy with opportunistic salpingectomy compared to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For surgery-related adverse events, there were insufficient data to assess whether there was any difference in both intraoperative (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.11 to 3.94; 5 studies, 286 participants; very low-quality evidence) and short-term postoperative (OR 0.13, 95% CI 0.01 to 2.14; 3 studies, 152 participants; very low-quality evidence) complication rates between hysterectomy with opportunistic salpingectomy and hysterectomy without opportunistic salpingectomy because the number of surgery-related adverse events was very low. For postoperative hormonal status, the results were compatible with no difference, or with a reduction in anti-Müllerian hormone (AMH) that would not be clinically relevant (mean difference (MD) -0.94, 95% CI -1.89 to 0.01; I2 = 0%; 5 studies, 283 participants; low-quality evidence). A reduction in AMH would be unfavourable, but due to wide CIs, the postoperative change in AMH can still vary from a substantial decrease to even a slight increase. There were no eligible studies reporting on one of our primary outcomes - the incidence of ovarian cancer specifically after hysterectomy with or without opportunistic salpingectomy. In our meta-analyses we found insufficient data to assess whether there was any difference in surgical adverse events, with a very low number of events in women undergoing hysterectomy with and without opportunistic salpingectomy. For postoperative hormonal status we found no evidence of a difference between the groups. The maximum difference in time to menopause, calculated from the lower limit of the 95% CI and the natural average AMH decline, would be approximately 20 months, which we consider to be not clinically relevant. However, the results should be interpreted with caution and even more so in very young women for whom a difference in postoperative hormonal status is potentially more clinically relevant. Therefore, there is a need for research on the long-term effects of opportunistic salpingectomy during hysterectomy, particularly in younger women, as results are currently limited to six months postoperatively. This limit is especially important as AMH, the most frequently used marker for ovarian reserve, recovers over the course of several months following an initial sharp decline after surgery. In light of the available evidence, addition of opportunistic salpingectomy should be discussed with each woman undergoing a hysterectomy for benign indication, with provision of a clear overview of benefits and risks. | We found seven randomised controlled trials comparing hysterectomy with salpingectomy to hysterectomy without salpingectomy. They included a total of 350 women undergoing a hysterectomy for benign conditions of the female reproductive tract. The evidence is current to January 2019. We found no studies that reported ovarian cancer incidence after hysterectomy with salpingectomy to hysterectomy without salpingectomy. The number of complications that occur after hysterectomy is generally very low. This means that only a few complications occurred in the trials included in this review and we were unable to make a good comparison of complication rates. We found no evidence for any difference in onset of menopause after hysterectomy with salpingectomy. Our results suggest that the AMH concentrations after hysterectomy with salpingectomy would be between 1.89 pmol/L lower and 0.01 pmol/L higher than after hysterectomy without salpingectomy. The minimum difference in AMH concentration (0.01 pmol/L) represents no difference in the onset of menopause. The maximum difference in AMH concentration (1.89 pmol/L) shows that menopause could occur up to 20 months earlier after hysterectomy with salpingectomy compared to hysterectomy without salpingectomy. This result is calculated from the average decline of AMH per year. The evidence was of very low to low quality. The main limitations in the evidence were a low number of complications, meaning no comparison could be made, and differences in outcome measures of the included studies. Also, the total numbers of included studies and included women were low. |
We did not identifiy any new trials for inclusion or exclusion in this 2014 update. One study involving 110 participants (55 participants in each group) met our inclusion criteria. The corticosteroid (prednisolone) showed a benefit in shortening the median time to resolution of headaches (five days in the treatment group versus 13 days in the control group, P value < 0.0001). Corticosteroids were also associated with smaller numbers of participants who still had headaches after a two-week course of treatment (9.1% versus 45.5%, P value < 0.0001). The number of patients who needed repeat lumbar puncture was also smaller in the treatment group (12.7% versus 40%, P value = 0.002). There was a reduction in the median time of analgesic use in participants receiving corticosteroids (10.5 versus 25.0, P value = 0.038). There were no reported adverse effects from prednisolone in the treatment group. Corticosteroids significantly help relieve headache in patients with eosinophilic meningitis, who have a pain score of four or more on a visual analogue scale. However, there is only one RCT supporting this benefit and this trial did not clearly mention allocation concealment and stratification. Therefore, we agreed to grade our included study as a moderate quality trial. Future well-designed RCTs are necessary. | We conducted a systematic review and meta-analysis of randomised controlled trials of corticosteroids for treating eosinophilic meningitis. The evidence is current to December 2014. We found only one randomised controlled trial that matched our criteria. This trial included 129 patients (63 in the treatment group, prednisolone 60 mg/day, divided into three doses for two weeks and 66 in the control group, placebo). However,19 patients were lost to follow-up. The included study showed that the median time to resolution of headaches was lower in the group treated with prednisolone (10.5 days versus 25 days) and the number of patients who still had headaches after 14 days was lower in the prednisolone group compared to the control (9.1% versus 45.5%). There were statistically significant differences, which favoured the treatment group, in other outcomes including the frequency of acetaminophen (paracetamol) use (median of number of times used) amongst those who still had headaches after 14 days of prednisolone treatment and the mean time until complete disappearance of headache. The number of patients who needed repeat lumbar puncture was also smaller in the treatment group. There were no reported adverse effects from prednisolone in the treatment group. Corticosteroids significantly help relieve headache in patients with eosinophilic meningitis, who have a pain score of four or more on a visual analogue scale. Given the lack of allocation concealment and blinding (especially in a trial with subjective outcomes), and the attrition (loss of participants), we graded our evidence as moderate quality. |
Twenty-one RCTs enrolling a total of 1424 participants were eligible for this review. All were RCTs, but methods used for random allocation were not always clear. Allocation concealment, blinding of the intervention, and blinding of outcome assessments most often were satisfactory. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days) but no reduction in mortality at 36 weeks, at discharge, or at latest reported age. Benefits of delayed steroid treatment included reductions in failure to extubate by 3, 7, or 28 days; bronchopulmonary dysplasia both at 28 days of life and at 36 weeks' postmenstrual age; need for late rescue treatment with dexamethasone; discharge on home oxygen; and death or bronchopulmonary dysplasia both at 28 days of life and at 36 weeks' postmenstrual age. Data revealed a trend towards increased risk of infection and gastrointestinal bleeding but no increase in risk of necrotising enterocolitis. Short-term adverse affects included hyperglycaemia, glycosuria, and hypertension. Investigators reported an increase in severe retinopathy of prematurity but no significant increase in blindness. Trial results showed a trend towards reduction in severe intraventricular haemorrhage, but only five studies enrolling 247 infants reported this outcome. Trends towards an increase in cerebral palsy or abnormal neurological examination findings were partly offset by a trend in the opposite direction involving death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability and the combined rate of death or major neurosensory disability were not significantly different between steroid and control groups. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure, or growth, although there were fewer participants with a clinically important reduction in forced expired volume in one second (FEV1) on respiratory function testing in the dexamethasone group. GRADE findings were high for all major outcomes considered, but review authors degraded the quality of evidence by one level because we found evidence of publication bias (bronchopulmonary dysplasia at 36 weeks). Benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. This review of postnatal systemic corticosteroid treatment for bronchopulmonary dysplasia initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of studies determining long-term outcomes is limited in some cases (some studies assessed surviving children only before school age, when some important neurological outcomes cannot be determined with certainty), and no studies were sufficiently powered to detect increased rates of important adverse long-term neurosensory outcomes. Evidence showing both benefits and harms of treatment and limitations of available evidence suggests that it may be prudent to reserve the use of late corticosteroids for infants who cannot be weaned from mechanical ventilation, and to minimise both dose and duration for any course of treatment. | We reviewed all clinical trials in preterm babies that gave corticosteroids after the first week after birth and provided data on rates of bronchopulmonary dysplasia later in the newborn period. This review of trials indicates that giving corticosteroids to infants at least seven days after birth produces short-term benefits in reducing the need for assisted ventilation and the rate of bronchopulmonary dysplasia, perhaps also reducing death during the first 28 days of life. However, high doses in particular are associated with short-term side effects such as bleeding from the stomach or bowel, higher blood pressure, and difficulty tolerating glucose. In contrast with early use of corticosteroids (in the first week of life), we found little evidence of long-term complications and uncertainty regarding long-term problems. It seems wise to limit late use of corticosteroids to babies who cannot be weaned from assisted ventilation, and to minimise the dose and duration of any course of treatment. Overall the quality of evidence supporting our conclusions was high. |
The studies: we included four cross-over studies, with a total of 113 children aged 5 to 13 years, most of whom (83%) were boys. We included two studies with five-year-old children since we were unable to obtain the disaggregated data for those aged six years and above, and all other participants were in our target age range. All participants resided in the USA. The duration of treatment in the cross-over phase was one week for each dose of methylphenidate. Studies used a range of outcome scales, rated by parents, teachers or both; clinicians; or programme staff. We report parent-rated outcomes separately. Risk of bias: we considered three trials to be at high risk of bias due to selective reporting and all trials to be at unclear risk of bias for blinding of participants and assessors, due to the potential for recognising the side effects of methylphenidate. We judged all trials to be at low or unclear risk of bias for other items. Primary outcomes: the meta-analysis suggested that high-dose methylphenidate (0.43 mg/kg/dose to 0.60 mg/kg/dose) had a significant and clinically relevant benefit on hyperactivity, as rated by teachers (SMD −0.78, 95% confidence interval (CI) −1.13 to −0.43; 4 studies, 73 participants; P < 0.001; low-quality evidence) and parents (mean difference (MD) −6.61 points, 95% CI −12.19 to −1.03, rated on the hyperactivity subscale of the Aberrant Behviour Checklist, range 0 to 48; 2 studies, 71 participants; P = 0.02; low-quality evidence). Meta-analysis also showed a significant but not clinically relevant benefit on teacher-rated inattention (MD −2.72 points, 95% CI −5.37 to −0.06, rated on the inattention subscale of the Swanson, Nolan and Pelham, Fourth Version questionnaire, range 0 to 27; 2 studies, 51 participants; P = 0.04; low-quality evidence). There were inadequate data to conduct a meta-analysis on the symptom of impulsivity. There was no evidence that methylphenidate worsens the core symptoms of ASD or benefits social interaction (SMD −0.51, 95% CI −1.07 to 0.05; 3 studies, 63 participants; P = 0.07; very low-quality evidence), stereotypical behaviours (SMD −0.34, 95% CI −0.84 to 0.17; 3 studies, 69 participants; P = 0.19; low-quality evidence), or overall ASD (SMD −0.53, 95% CI −1.26 to 0.19; 2 studies, 36 participants; P = 0.15; low-quality evidence), as rated by teachers. There were inadequate data to conduct a meta-analysis on the symptom of impaired communication. Secondary outcomes: no data were available for the secondary outcomes of caregiver well-being; need for institutionalisation, special schooling options or therapy to achieve learning outcomes; or overall quality of life. No trials reported serious adverse events. The only adverse effect that was significantly more likely with treatment was reduced appetite as rated by parents (risk ratio 8.28, 95% CI 2.57 to 26.73; 2 studies, 74 participants; P < 0.001; very low-quality evidence). Subgroup analysis by dose did not identify any significant differences in effect on our primary outcomes between low-, medium- or high-dose ranges. We found that short-term use of methylphenidate might improve symptoms of hyperactivity and possibly inattention in children with ASD who are tolerant of the medication, although the low quality of evidence means that we cannot be certain of the true magnitude of any effect. There was no evidence that methylphenidate has a negative impact on the core symptoms of ASD, or that it improves social interaction, stereotypical behaviours, or overall ASD. The evidence for adverse events is of very low quality because trials were short and excluded children intolerant of methylphenidate in the test-dose phase. Future RCTs should consider extending the duration of treatment and follow-up. The minimum clinically important difference also needs to be confirmed in children with ASD using outcome scales validated for this population. | We looked for studies that compared children receiving methylphenidate at any dose to placebo (a dummy pill which looks like methylphenidate but has no known effects). We were most interested in investigating the effect of the drug on symptoms of ADHD (inattention, impulsivity and hyperactivity) and ASD (impairments in social interaction and communication, and repetitive, restricted or stereotypical behaviours), but we also looked for information on side effects, caregiver well-being, the need for special schooling or institutionalisation, and children's overall quality of life. What are the main results of the review? We found four studies involving 113 children aged 5 to 13 years and comparing methylphenidate versus placebo. We included two studies with five-year-old children because we were unable to separate the data for those aged six years and above, and all other participants were in our target age range. In all of these studies, children took different doses of methylphenidate (low, medium or high) for one week and placebo for another week, and their caregivers (including parents, teachers and clinicians) rated their symptoms at the end of each week. Children who could not tolerate methylphenidate in the test-dose week (where a dose of medication is given to test the safety and tolerability of the drug) did not participate in the study. All of the studies took place in the USA. We found that methylphenidate may improve hyperactivity, as assessed by parents and teachers, in the short term. Teachers also tended to report an improvement in children taking methylphenidate in relation to inattention, social interaction, repetitive behaviours, and overall ASD symptoms. However, the studies only lasted for about four weeks, so we do not know if there are any benefits or risks in the long term. There was not enough evidence to say whether methylphenidate has any effect on impulsivity or communication. Teachers and clinicians tended to report more improvement than parents. We cannot be confident about these findings, mainly because parents and teachers may have recognised which treatment the children were on. The size of the improvement was not very large, except in the case of hyperactivity, where it was probably large enough to really notice the difference. Most of the improvements, except for the improvements in hyperactivity and inattention, could have happened by chance even if methylphenidate is not really effective. We cannot say anything about the likelihood of any harmful effects from methylphenidate, partly because children who had harmful effects prior to the studies, or in the test-dose phase, are less likely to have participated in the studies. How up-to-date is this review? The evidence is current to November 2016. |
Four studies with a total of 277 participants were included. These studies assessed the efficacy of FMT for treatment of UC in adults; no eligible trials were found for the treatment of CD. Most participants had mild to moderate UC. Two studies were conducted in Australia, one study was conducted in Canada, and another in the Netherlands. Three of the included studies administered FMT via the rectal route and one study administered FMT via the nasoduodenal route. Three studies were rated as low risk of bias. One study (abstract publication) was rated as unclear risk of bias. Combined results from four studies (277 participants) suggest that FMT increases rates of clinical remission by two-fold in patients with UC compared to controls. At 8 weeks, 37% (52/140) of FMT participants achieved remission compared to 18% (24/137) of control participants (RR 2.03, 95 % CI, 1.07 to 3.86; I² = 50%; low certainty evidence). One study reported data on relapse at 12 weeks among participants who achieved remission. None of the FMT participants (0/7) relapsed at 12 weeks compared to 20% of control participants (RR 0.28, 95% CI 0.02 to 4.98, 17 participants, very low certainty evidence). It is unclear whether there is a difference in serious adverse event rates between the intervention and control groups. Seven per cent (10/140) of FMT participants had a serious adverse event compared to 5% (7/137) of control participants (RR 1.40, 95% CI 0.55 to 3.58; 4 studies; I² = 0%; low certainty evidence). Serious adverse events included worsening of UC necessitating intravenous steroids or surgery; infection such as Clostridium difficile and cytomegalovirus, small bowel perforation and pneumonia. Adverse events were reported by two studies and the pooled data did not show any difference between the study groups. Seventy-eight per cent (50/64) of FMT participants had an adverse event compared to 75% (49/65) of control participants (RR 1.03, 95% CI 0.81 to 1.31; I² = 31%; moderate certainty evidence). Common adverse events included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Four studies reported on clinical response at 8 weeks. Forty-nine per cent (68/140) of FMT participants had a clinical response compared to 28% (38/137) of control participants (RR 1.70, 95% CI 0.98 to 2.95, I² = 50%, low certainty evidence). Endoscopic remission at 8 weeks was reported by three studies and the combined results favored FMT over the control group. Thirty per cent (35/117) of FMT participants achieved endoscopic remission compared to 10% (11/112) of control participants (RR 2.96, 95 % CI 1.60 to 5.48, I² = 0%; low certainty evidence). Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time. Additional high-quality studies are needed to further define the optimal parameters of FMT in terms of route, frequency, volume, preparation, type of donor and the type and disease severity. No studies assessed efficacy of FMT for induction of remission in CD or in pediatric participants. In addition, no studies assessed long-term maintenance of remission in UC or CD. Future studies are needed to address the therapeutic benefit of FMT in CD and the long-term FMT-mediated maintenance of remission in UC or CD. | We found four studies (277 participants) that assessed the effectiveness of stool transplantation for the treatment of adults with active UC. We did not find any randomized studies that assessed stool transplantation in participants with CD or in children. In addition, we did not find any studies that assessed maintenance of remission in participants with inactive IBD. Two of the identified studies were conducted in Australia, one in Canada, and one in the Netherlands. The dose, route, frequency, volume, type of donor, and severity of disease of recipients varied among the studies. Combined results from four studies including 277 participants indicated that stool transplantation increased rates of resolution of symptoms (also termed clinical remission) of UC patients by two-fold compared to controls. At 8 weeks after transplantation, 37% (52/140) of participants in the stool transplant group were in remission compared to 18% (24/137) of participants in the control group. Combined data from the same four studies showed similar rates of serious side effects. Seven per cent (10/140) of the stool transplantation group had a serious side effect compared to 5% (7/137) of the control group. Serious side effects included worsening of ulcerative colitis that required intravenous steroids or surgery; infections such as Clostridium difficile and cytomegalovirus, small bowel perforation, and pneumonia. The incidence of side effects were similar in both stool transplant and control groups and included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Data from three included studies showed that stool transplantation helped improve UC when the assessment of disease resolution was made by the appearance of the intestinal lining when visualized with an endoscope. We rated the overall quality of the evidence using the GRADE approach, which takes into account the type of studies, methodological flaws within studies, the consistency in reporting of results across studies, method of measurement of effect of intervention and statistical confidence in the summary estimates. Based on these criteria, we judged the overall quality of the evidence for most of the outcomes to be low based on a small number of events and participants and inconsistency of results. Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious side effects. Thus, no firm conclusions can be drawn regarding the benefits and harms of stool transplantation in people with active UC. We did not find any studies that addressed treatment of CD with stool transplantation or studies that assessed stool transplantation in children with IBD. In addition, we did not find any studies that assessed long-term maintenance of remission in participants with inactive IBD. More studies are needed to enhance the knowledge about use of stool transplantation for treatment of IBD. |
Five studies were identified which enrolled a total of 1302 infants. In two studies allocation was randomised and the caregivers were blinded to intervention group. In the other three studies, allocation was quasi-randomised and the caregivers were not blinded. Pooled analysis of the four trials reporting effect on death showed a significant reduction in the rate of death in the group resuscitated with room air [typical RR 0.71 (0.54, 0.94), typical RD -0.05 (-0.08, -0.01), NNT 20 (12, 100)]. There were no significant differences between the groups with respect to rates of grade 2 or 3 hypoxic ischaemic encephalopathy. One of the four trials reported a statistically significant difference in median 5 minute Apgar scores, favouring the group allocated to room air. However, the absolute difference between the medians was small and there were no significant differences in the median 10 minute Apgar scores in the three trials reporting this outcome. One trial followed up a selected subgroup of survivors to 18-24 months. There were no significant differences in rates of adverse neurodevelopmental outcomes including cerebral palsy and failure to achieve various milestones; however, the proportion of eligible patients seen was less than 70%. Analyses that were planned for this review, but not able to be carried out because of lack of published data, included a sub-analysis stratified by gestational age and assessments of the effect on bronchopulmonary dysplasia and retinopathy of prematurity. There is insufficient evidence at present on which to recommend a policy of using room air over 100% oxygen, or vice versa, for newborn resuscitation. A reduction in mortality has been seen in infants resuscitated with room air, and no evidence of harm has been demonstrated. However, the small number of identified studies and their methodologic limitations dictate caution in interpreting and applying these results. We note the use of back-up 100% oxygen in more than a quarter of infants randomised to room air. Therefore, on the basis of currently available evidence, if one chooses room air as the initial gas for resuscitation, supplementary oxygen should continue to be made available. | The authors of this Cochrane review questioned whether resuscitation with room air resulted in fewer deaths or disabilities than 100% oxygen. After searching the literature, they found five studies. There were a total of 1302 infants in these studies; 24% of them were premature. In the studies, fewer babies died when resuscitated with room air than with 100% oxygen. Many of the babies resuscitated with room air also got some oxygen as a supplement, making it difficult to compare the two groups. There were also other problems with the way the studies were carried out. The authors of the Cochrane review concluded that there is not enough evidence to recommend room air over 100% oxygen, or vice versa. |
We included three RCTs that randomly assigned a total of 1089 participants recruited from 43 ICUs in Australia, Canada, Saudi Arabia, Spain and the USA. Risk of bias of the included studies was low. Only data for mortality and barotrauma could be combined in the meta-analysis. We downgraded the quality of evidence for the three mortality outcomes on the basis of serious imprecision around the effect estimates. For mortality in hospital, the RR with PCV compared with VCV was 0.83 (95% CI 0.67 to 1.02; three trials, 1089 participants; moderate-quality evidence), and for mortality in the ICU, the RR with PCV compared with VCV was 0.84 (95% CI 0.71 to 0.99; two trials, 1062 participants; moderate-quality evidence). One study provided no evidence of clear benefit with the ventilatory mode for mortality at 28 days (RR 0.88, 95% CI 0.73 to 1.06; 983 participants; moderate-quality evidence). The difference in effect on barotrauma between PCV and VCV was uncertain as the result of imprecision and different co-interventions used in the studies (RR 1.24, 95% CI 0.87 to 1.77; two trials, 1062 participants; low-quality evidence). Data from one trial with 983 participants for the mean duration of ventilation, and from another trial with 78 participants for the mean number of extrapulmonary organ failures that developed with PCV or VCV, were skewed. None of the trials reported on infection during ventilation or quality of life after discharge. Currently available data from RCTs are insufficient to confirm or refute whether pressure-controlled or volume-controlled ventilation offers any advantage for people with acute respiratory failure due to acute lung injury or acute respiratory distress syndrome. More studies including a larger number of people given PCV and VCV may provide reliable evidence on which more firm conclusions can be based. | The three randomized trials compared PCV versus VCV in a total of 1089 adults with ALI/ARDS from 43 ICUs in five high-income countries. None of the trials were industry-funded. The evidence is current to October 2014. We could not be sure whether the proportions of patients who died in hospital were very different between those treated with PCV and with VCV. For every 1000 persons treated with VCV, 636 deaths were reported. On the basis of our results, we could expect to see between 210 fewer deaths and 13 more deaths with PCV. We found that effects on mortality in the ICU and on mortality at 28 days were similarly uncertain. Our results include the possibility that VCV or PCV could be better for reducing the duration of ventilation or the development of traumatic lung damage caused by ventilation (barotrauma). None of the studies provided reliable information regarding to what extent failure of other organs would be impacted by the type of ventilation, nor did they provide information on differences in infection risk or quality of life following discharge from intensive care. The overall evidence for mortality was of moderate quality. For outcomes such as duration of ventilation, barotrauma and organ failure, evidence was limited by the small numbers studied, the different methods used in the studies or differences in reporting of results, which made interpretation difficult. Available evidence is insufficient to confirm whether PCV offers any advantage over VCV in improving outcomes for people with acute lung injury on ventilator machines. More studies including a larger number of people given PCV and VCV may provide reliable evidence on which more firm conclusions can be based. |
Eleven trials were identified of which seven were excluded and four with 312 participants were included. No trial reported live birth outcomes. One trial compared gonadotropin-releasing hormone (GnRH) agonist with GnRH antagonist. There was no evidence of a difference for clinical pregnancy rate (CPR), however the number of mature oocytes retrieved (NMOR) was greater with GnRH agonists (MD -1.60, 95% CI -2.44 to -0.76) and the ovarian response was increased (estradiol (E2) levels on day of human chorionic gonadotropin (hCG) injection) (MD -456.30, 95% CI -896.06 to -16.54). Surgery (aspiration or cystectomy) versus expectant management (EM) showed no evidence of a benefit for clinical pregnancy with either technique. Aspiration was associated with greater NMOR (MD 0.50, 95% CI 0.02 to 0.98) and increased ovarian response (E2 levels on day of hCG injection) (MD 685.3, 95% CI 464.50 to 906.10) compared to EM.Cystectomy was associated with a decreased ovarian response to controlled ovarian hyperstimulation (COH) (MD -510.00, 95% CI -676.62 to -343.38); no evidence of an effect on the NMOR compared to EM. Aspiration versus cystectomy showed no evidence of a difference in CPR or the NMOR. There was no evidence of an effect on reproductive outcomes in any of the four included trials. Further RCTs of management of endometrioma in women undergoing ART are required. | This review aimed to determine which treatment approach was better for women with subfertility and endometriomata who were undergoing assisted reproductive technology (ART). Four trials were identified. A gonadotropin-releasing hormone (GnRH) agonist showed a positive treatment effect on the ovarian response to controlled ovarian hyperstimulation (COH) and the number of mature oocytes retrieved compared to GnRH antagonist. The evidence for surgery was limited but aspiration was associated with a greater ovarian response than expectant management (a wait and see approach). Further randomised controlled trials of interventions for the management of endometrioma in women undergoing ART are required. |
We identified eight trials that met the inclusion criteria. One trial including 17 surgical trainees did not contribute to the meta-analysis. We included seven trials (249 surgical trainees belonging to various postgraduate years ranging from year one to four) in which the participants were randomised to supplementary box model training (122 trainees) versus standard training (127 trainees). Only one trial (50 trainees) was at low risk of bias. The box trainers used in all the seven trials were video trainers. Six trials were conducted in USA and one trial in Canada. The surgeries in which the final assessments were made included laparoscopic total extraperitoneal hernia repairs, laparoscopic cholecystectomy, laparoscopic tubal ligation, laparoscopic partial salpingectomy, and laparoscopic bilateral mid-segment salpingectomy. The final assessments were made on a single operative procedure. There were no deaths in three trials (0/82 (0%) supplementary box model training versus 0/86 (0%) standard training; RR not estimable; very low quality evidence). The other trials did not report mortality. The estimated effect on serious adverse events was compatible with benefit and harm (three trials; 168 patients; 0/82 (0%) supplementary box model training versus 1/86 (1.1%) standard training; RR 0.36; 95% CI 0.02 to 8.43; very low quality evidence). None of the trials reported patient quality of life. The operating time was significantly shorter in the supplementary box model training group versus the standard training group (1 trial; 50 patients; MD -6.50 minutes; 95% CI -10.85 to -2.15). The proportion of patients who were discharged as day-surgery was significantly higher in the supplementary box model training group versus the standard training group (1 trial; 50 patients; 24/24 (100%) supplementary box model training versus 15/26 (57.7%) standard training; RR 1.71; 95% CI 1.23 to 2.37). None of the trials reported trainee satisfaction. The operating performance was significantly better in the supplementary box model training group versus the standard training group (seven trials; 249 trainees; SMD 0.84; 95% CI 0.57 to 1.10). None of the trials compared box model training versus animal model training or versus different methods of box model training. There is insufficient evidence to determine whether laparoscopic box model training reduces mortality or morbidity. There is very low quality evidence that it improves technical skills compared with standard surgical training in trainees with limited previous laparoscopic experience. It may also decrease operating time and increase the proportion of patients who were discharged as day-surgery in the first total extraperitoneal hernia repair after box model training. However, the duration of the benefit of box model training is unknown. Further well-designed trials of low risk of bias and random errors are necessary. Such trials should assess the long-term impact of box model training on clinical outcomes and compare box training with other forms of training. | We identified and included seven trials in which 249 surgical trainees with limited previous laparoscopic experience received either box model training in addition to their standard apprenticeship training (122 trainees) versus standard apprenticeship training alone (127 trainees). The choice of whether the trainees received supplementary box model training was made in a random method similar to the toss of a coin. Six trials were conducted in USA and one trial in Canada. After supplementary box model training or standard training, the performance of the trainees was evaluated on their first operation after supplementary box model training and during the first operation in humans after an equivalent time after standard training. Different trials assessed the performance in different operations and all these operations were minor to moderate operations. Three trials including 168 trainees reported the complications that the patients developed during or immediately after the operation. There were no deaths in either group in 168 operations performed by 168 trainees and we could not tell whether laparoscopic box model training led to major complications (one major complication in one patient operated by a trainee who underwent standard training out of 86 operations performed by trainees who underwent standard training as compared with no major complications in 82 operations performed by trainees who underwent box model training). None of the trials reported patient quality of life. One trial reported a small reduction in operating time of just over six minutes in the supplementary box model training group. The remaining trials did not report operating time. In one trial, the proportion of patients who were discharged as day-surgery was significantly higher in the supplementary box model training group (24/24 (100%)) compared with the standard training group (15/26 (57.7%)). The remaining trials did not report the proportion of people who stayed overnight. None of the trials reported trainee satisfaction. The operating performance as assessed by surgical experts was significantly better in the supplementary box model training group compared with the standard training group. None of the trials compared box model training compared with animal model training or compared with different methods of box model training. Laparoscopic box model training appears to improve technical skills compared with standard surgical training in trainees with limited previous laparoscopic experience. It may also decrease operating time and decrease the proportion of patients who require overnight stay in the first hernia repair operation that the trainee performed after box model training. However, the duration of the benefit of box model training (ie, whether such benefit continues in subsequent operations) is unknown. Only one trial including 50 trainees was at low risk of bias (no risk of arriving at wrong conclusions because of favouritism by the researchers). 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. Such trials should assess the long-term impact of box model training on clinical outcomes. |
We identified 26 studies (8835 participants). Risk of bias was high in 17, unclear in 6and low in three studies. There was high risk of attrition bias in six studies. Only two studies measured AKI. The use of NSAIDs had uncertain effects on the incidence of AKI compared to placebo (7066 participants: RR 1.79, 95% CI 0.40 to 7.96; I2 = 59%; very low certainty evidence). One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group. Moreover, both of these studies were examining NSAIDs for indications other than analgesia and therefore utilised relatively low doses. Compared to placebo, NSAIDs may slightly increase serum SCr (15 studies, 794 participants: MD 3.23 μmol/L, 95% CI -0.80 to 7.26; I2 = 63%; low certainty evidence). Studies displayed moderate to high heterogeneity and had multiple exclusion criteria including age and so were not representative of patients undergoing surgery. Three of these studies excluded patients if their creatinine rose post-operatively. NSAIDs may make little or no difference to post-operative urine output compared to placebo (6 studies, 149 participants: SMD -0.02, 95% CI -0.31 to 0.27). No reliable conclusions could be drawn from these studies due to the differing units of measurements and measurement time points. It is uncertain whether NSAIDs leads to the need for RRT because the certainty of this evidence is very low (2 studies, 7056 participants: RR 1.57, 95% CI 0.49 to 5.07; I2 = 26%); there were few events and the results were inconsistent. It is uncertain whether NSAIDs lead to more deaths (2 studies, 312 participants: RR 1.44, 95% CI 0.19 to 11.12; I2 = 38%) or increased the length of hospital stay (3 studies, 410 participants: MD 0.12 days, 95% CI -0.48 to 0.72; I2 = 24%). Overall NSAIDs had uncertain effects on the risk of post-operative AKI, may slightly increase post-operative SCr, and it is uncertain whether NSAIDs lead to the need for RRT, death or increases the length of hospital stay. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further larger studies using the Kidney Disease Improving Global Outcomes definition for AKI including patients with co-morbidities are required to confirm these findings. . | We identified 26 studies studying 8835 participants. Risk of bias was high in 17, unclear in six studies and low in three studies. The use NSAIDs had uncertain effects on the incidence of AKI compared to placebo. Quality of evidence was very low due to inconsistencies between the two studies. One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group and both of these studies examined much lower doses of NSAIDs than would usually be used for pain relief. NSAIDs may slightly increase serum creatinine (a marker of kidney function which rises in kidney failure) compared with placebo. Quality of evidence was low. These studies only included fit, healthy patients. No reliable conclusions could be drawn from the studies examining urine output due to the different methods of measuring this. It is uncertain whether the use of NSAIDs leads to an increased need for renal replacement therapy (dialysis), more deaths, or increased length of hospital stay. NSAIDs have uncertain effects on the rates of AKI when used in patients with normal kidney function following surgery. It is uncertain whether NSAIDs increase the need for dialysis. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further studies including patients with other health problems are required. |
Three RCTs (involving 386 women) were included in the review. Peri-implantation low molecular weight heparin (LMWH) during IVF/ICSI was given at or after egg collection or at embryo transfer in these studies. The characteristics of the participants differed across studies. One included women having their first IVF cycle, with no blood clotting disorder; another included women with at least one blood clotting disorder and the third included women who had undergone at least two previous unsuccessful ART cycles. Our findings differed according to choice of statistical model. When we used a fixed effect analysis, the evidence suggested that peri-implantation heparin was associated with an improvement in live birth rate compared with placebo or no heparin (odds ratio (OR) 1.77, 95% confidence interval (CI) 1.07 to 2.90, three studies, 386 women, I2 = 51%, very low quality evidence) and also an improvement in the clinical pregnancy rate (OR 1.61, 95% CI 1.03 to 2.53, three studies, 386 women, I2 = 29%, low quality evidence). However when a random effects model was used there was no longer a difference between the groups for either live birth (OR 1.85, 95% CI 0.80 to 4.24) or clinical pregnancy (OR 1.66, 95% CI 0.94 to 2.90). Moreover there was high heterogeneity (I2 = 51%) for the analysis of live birth. Adverse events were poorly reported in all the included studies. Events such as bleeding, and thrombocytopenia were reported in women receiving heparin and affected 5-7% of women in the heparin group in one study. However no studies reported data suitable for analysis and so no firm conclusions could be drawn regarding adverse effects. The main limitations in the evidence were inconsistency, imprecision and inadequate reporting of adverse events. It is unclear whether peri-implantation heparin in assisted reproduction treatment (ART) cycles improves live birth and clinical pregnancy rates in subfertile women, as the evidence was sensitive to choice of statistical model and no benefit was apparent when a random effects model was used. Side effects have been reported with use of heparin and no firm conclusions can be drawn regarding its safety. Our results do not justify the use of heparin in this context, except in well-conducted research trials. These findings need to be further investigated with well-designed, adequately powered, double-blind, randomised, placebo-controlled, multicentre trials. Further investigations could also focus on the effects of the local (uterine) and non-systemic application of heparin during ART. | Three studies with 386 participants were included in the review. All participants were subfertile women undergoing assisted reproduction. Their characteristics differed across studies. One study included women having their first IVF cycle, with no blood clotting disorder. Another study included women with at least one blood clotting disorder. The third study included women with at least two previous unsuccessful assisted reproduction treatment cycles. In all cases a daily injection of low molecular weight heparin was given to women from the time of egg collection or embryo transfer during assisted reproduction. Control groups received placebo or no treatment. There were no issues with source of funding in any of the studies. The evidence is current to May 2013. Key Results It is unclear whether peri-implantation heparin in assisted reproduction treatment (ART) cycles improves live birth and clinical pregnancy rates in subfertile women. Although there was some suggestion of benefit, this disappeared when an alternative method of analysis was used. Heparin had side effects such as bruising and bleeding, but no conclusions could be drawn regarding its safety because none of the studies reported comparative data on adverse effects. The evidence does not justify the use of heparin except in well-designed clinical research trials. Such trials are a priority. Quality of Evidence The evidence was of low or very low quality, mainly due to imprecision, inconsistency and inadequate reporting of advere events. Further well-designed randomised controlled trials with larger sample sizes are needed to clarify the possible role of heparin in assisted reproduction. |
Thirty-two trials (9605 patients) were included. For symptomatic failure rates, no difference between three-day and 5-10 day antibiotic regimen was seen short-term (RR 1.06, 95% CI 0.88 to 1.28) and long-term follow-up (RR 1.09, 95% CI 0.94 to 1.27). Comparison of the bacteriological failure rates showed that three-day therapy was less effective than 5-10 day therapy for the short-term follow-up, however this difference was observed only in the subgroup of trials that used the same antibiotic in the two treatment arms (RR 1.37, 95% CI 1.07 to 1.74, P = 0.01). This difference was more significant at long-term follow-up (RR 1.43, 95% CI 1.19 to 1.73, P = 0.0002). Adverse effects were significantly more common in the 5-10 day treatment group (RR 0.83, 95% CI 0.74 to 0.93, P = 0.0010). Results were consistent for subgroup and sensitivity analyses. Three days of antibiotic therapy is similar to 5-10 days in achieving symptomatic cure during uncomplicated UTI treatment, while the longer treatment is more effective in obtaining bacteriological cure. In spite of the higher rate of adverse effects, treatment for 5-10 days could be considered for treatment of women in whom eradication of bacteriuria is important. | In this review we included all studies that compared three-day therapy with longer treatment (five days or more). Three days of treatment were adequate to achieve symptomatic relief for most patients, but it appears that longer therapy is better in terms of bacteria elimination from the urine, no matter what antibiotic is used. Longer therapy for UTI is related to higher rate of adverse reactions to the antibiotics used. Pending further research, it could be considered for women in whom eradication of bacteria in the urine is important. |
We included 16 eligible trials with a total of 1251 infant participants. Trials were of variable methodological quality, with lack of allocation concealment and incomplete follow-up identified as major potential sources of bias. Trials (N = 11) that compared feeding infants with 'postdischarge formula' (energy density about 74 kcal/100 mL) versus standard term formula (about 67 kcal/100 mL) did not find consistent evidence of effects on growth parameters up to 12 to 18 months post term. GRADE assessments indicated that evidence was of moderate quality, and that inconsistency within pooled estimates was the main quality issue. Trials (N = 5) that compared feeding with 'preterm formula' (about 80 kcal/100 mL) versus term formula found evidence of higher rates of growth throughout infancy (weighted mean differences at 12 to 18 months post term: about 500 g in weight, 5 to 10 mm in length, 5 mm in head circumference). GRADE assessments indicated that evidence was of moderate quality, and that imprecision of estimates was the main quality issue. Few trials assessed neurodevelopmental outcomes, and these trials did not detect differences in developmental indices at 18 months post term. Data on growth or development through later childhood have not been provided. Recommendations to prescribe 'postdischarge formula' for preterm infants after hospital discharge are not supported by available evidence. Limited evidence suggests that feeding 'preterm formula' (which is generally available only for in-hospital use) to preterm infants after hospital discharge may increase growth rates up to 18 months post term. | We identified 16 eligible trials enrolling a total of 1251 infants through searches updated to 8 September 2016. These trials provide moderate-quality evidence that unrestricted feeding with nutrient-enriched (vs standard) formula does not have important effects on growth and development up to about 18 months of age. Long-term growth and development have not yet been assessed. Current recommendations to prescribe nutrient-enriched formula for preterm infants after hospital discharge are not supported by available evidence. |
We included six trials published between 2007 and 2014 that randomised 599 adult participants. Study size ranged from 46 to 158 participants. Participants were aged between 18 years and 80 years; we could not derive gender proportions, as participants' sex was not reported in all studies. One study was available in abstract form only. We did not find a significant difference in outcomes between people who exercised and those who did not exercise before receiving influenza vaccination. Pre-vaccination exercises included endurance activities such as walking or using a treadmill, and resistance activities included biceps curls and lateral raises. Five of the studies provided one session of exercise between 25 and 50 minutes. In five studies, exercise was undertaken on the same day as the vaccination. One study provided exercise over a period of eight weeks before vaccination, with one 2½ hour supervised session, plus daily home exercise practice of 45 minutes. Exercise intensity ranged from 55% to 85% of maximal heart rate. Control group participants undertook a range of activities, including quiet rest, sitting, reading, meditation or unspecified activity. One study reported numbers of people who contracted influenza; no significant difference was reported between exercise and no-exercise participants. None of the included studies reported complications related to influenza illness. Only one study, which we assessed as providing low-quality evidence, reported numbers of people who experienced adverse events. This study reported no significant difference in outcomes between people who exercised and those who did not. No studies reported numbers of working days or days lost related to influenza illness. Only two studies reported participant-centred outcomes. Overall, study quality was unclear; we assessed five of the six included studies to have at least four unclear 'Risk of bias' domains (allocation concealment, blinding of outcome assessment, selective reporting and other bias). Insufficient reporting in four studies about selective reporting did not provide enough information to enable judgement; only two studies were included in trials registers. From the available evidence, we found that exercising before influenza vaccination is neither beneficial nor harmful. However, study data were limited and of low quality. Small sample sizes, study design limitations, exercise types, and focus on biochemical rather than participant-centred outcomes strongly influenced our findings. | We looked at six studies that involved 599 people aged between 18 and 80 years that assessed exercise before flu vaccination. Exercises included walking or using a treadmill (endurance) and biceps curls and lateral raises (resistance) activities that ranged from 25 to 50 minutes per session. People in five studies did one session of exercise on the day of vaccination; in one study people exercised eight weeks before vaccination. Exercise was supervised in three studies. People not undertaking exercise (control group) were assessed after periods of quiet rest. Three studies did not report study funding sources; one received support from a drug company that donated flu vaccine, one from a professional society, and another from government agencies. We found no differences in numbers of people who caught flu or developed complications between people who exercised and those who did not before flu vaccination. Only one study reported how many people developed flu after exercise and vaccination. No studies reported complications related to flu; only one reported adverse events. None reported numbers of working or other days lost due to flu. No beneficial differences were reported between exercise and no-exercise groups before vaccination. Small numbers of people who were involved in the studies, limitations in study design, and different exercise types meant we were unable to draw robust conclusions about any benefits of exercise before vaccination. There appears to be no benefit or harm from exercising before receiving flu vaccination. Evidence quality was very low or low. More robust study designs that include enough people to enable assessment and analysis of findings may help to determine if exercise before vaccination can reduce numbers of people who develop flu or complications. We found that exercising before influenza vaccination is neither beneficial nor harmful. Small number of people in each included study, many types of exercises, and focus on blood examination instead of participant-centred outcomes strongly influenced our findings. |
We included two studies in the review, with a total of 344 participants. Studies lasted 8 weeks and 12 weeks and compared TC versus placebo. 0.1%. TC was applied in gel form to the painful area two to three times daily. Studies included in this review were subject to potential bias and were classified as of moderate or low quality. One drug manufacturer supported both studies. We found no top-tier evidence for TC in neuropathic pain. Second-tier evidence indicated slight improvement after the drug was used in study participants with painful diabetic neuropathy (PDN). A greater number of participants in the TC group had at least 30% reduction in pain compared with placebo (risk ratio (RR) 1.35, 95% confidence interval (CI) 1.03 to 1.77; number needed to treat for an additional beneficial outcome (NNTB) 8.33, 95% CI 4.3 to 50). Third-tier evidence indicated that TC was no better than placebo for achieving at least 50% reduction in pain intensity and on the Patient Global Impression of Change Scale. The two included studies could be subject to significant bias. We found no studies that reported other neuropathic pain conditions. The rate of adverse events did not differ between groups, with the exception of a higher incidence of mild skin reactions in the placebo group, which should have no clinical significance. Limited evidence from a small number of studies of moderate to low quality suggests that TC may provide some benefit in peripheral diabetic neuropathy. The drug may be useful in situations for which no better treatment options are available because of lack of efficacy, contraindications or adverse events. Additional trials are needed to assess TC in other neuropathic pain conditions and to determine how patients who have a chance to respond to the drug should be selected for treatment. | From these studies, we know that clonidine applied to the skin probably gives little benefit to patients with PDN, but we cannot be sure of this. Clonidine may provide partial pain relief to one out of eight people treated with it. We do not know how clonidine applied to the skin works in other neuropathic pain conditions. Treatment with the drug for short periods probably will not cause side effects, but we do not know from the studies if clonidine is safe for long-term use. Researchers have reported no differences in the total numbers of side effects among people taking TC or placebo. The most important message from this review is that clonidine applied to the skin may give partial pain relief for only some people with PDN. |
We identified three trials with 390 patients that compared cyclosporin A versus placebo. Two of them were assessed methodologically adequate with low-bias risk. Cyclosporin A did not significantly reduce mortality risk (RR 0.92, 95% CI 0.59 to 1.45), and mortality or liver transplantation (RR 0.85, 95% CI 0.60 to 1.20). Cyclosporin A significantly improved pruritus (SMD -0.38, 95% CI -0.63 to -0.14), but not fatigue. Cyclosporin A significantly reduced alanine aminotransferase (WMD -41 U/L, 95% CI -63 to -18) and increased serum albumin level (WMD 1.66 g/L, 95% CI 0.26 to 3.05). Significantly more patients experienced adverse events in the cyclosporin A group than in the placebo group, especially renal dysfunction (Peto odds ratio 5.56, 95% CI 2.52 to 12.27) and hypertension (SMD 0.88, 95% CI 0.27 to 1.48). We found no evidence supporting or refuting that cyclosporin A may delay death, death or liver transplantation, or progression of primary biliary cirrhosis. Cyclosporin A caused more adverse events than placebo, like renal dysfunction and hypertension. We do not recommend the use of cyclosporin A outside randomised clinical trials. | The findings in this review are based on three clinical trials with 390 patients. The drug cyclosporin A was tested against placebo. The primary findings of the review are that cyclosporin A has no effect on survival or progression of the disease (cirrhosis development). Patients given cyclosporin A experienced more adverse events than patients given placebo, especially renal dysfunction and hypertension. There was significant improvement in itching (pruritus) and liver biochemistry, which were secondary outcome measures. We cannot recommend the use of cyclosporin A outside randomised clinical trials. |
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