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Five studies on 588 adults and children were included concerning nurse-led care versus physician-led care. One study included 154 patients with uncontrolled asthma, while the other four studies including 434 patients with controlled or partly controlled asthma. The studies were of good methodological quality (although it is not possible to blind people giving or receiving the intervention to which group they are in). There was no statistically significant difference in the number of asthma exacerbations and asthma severity after treatment (duration of follow-up from six months to two years). Only one study had healthcare costs as an outcome parameter, no statistical differences were found. Although not a primary outcome, quality of life is a patient-important outcome and in the three trials on 380 subjects that reported on this outcome, there was no statistically significant difference (standardised mean difference (SMD) -0.03; 95% confidence interval (CI) -0.23 to 0.17). We found no significant difference between nurse-led care for patients with asthma compared to physician-led care for the outcomes assessed. Based on the relatively small number of studies in this review, nurse-led care may be appropriate in patients with well-controlled asthma. More studies in varied settings and among people with varying levels of asthma control are needed with data on adverse events and health-care costs. | We reviewed the medical literature to find randomised controlled trials on care delivered by specialised nurse compared to care by a doctor in the management of asthma. We found five studies on 588 adults and children. The studies were of good methodological quality. The number of asthma exacerbations (flare-ups) and the level of asthma severity did not differ at the end of the study period between the intervention and the control group. Only one study reported information about the costs associated with both kinds of care and there was no significant difference between them. There was also no difference in quality of life. We found no difference between nurse-led care and physician-led care. Based on the relatively small number of studies in this review, nurse-led care may be appropriate in patients with well-controlled asthma. More studies in varied settings and among people with varying levels of asthma control are needed with data on adverse events and healthcare costs. |
We identified six RCTs, involving 221 participants. The mean age of participants ranged from 59 to 70 years; the sample size ranged from 20 to 111 participants. Overall, we found that the risk of bias in the included studies was high, and the quality of evidence for all outcomes was low. Pooled data from four studies demonstrated that, on completion of the intervention period, exercise capacity (6MWD) was significantly higher in the intervention group than the control group (mean difference (MD) 63.33 m; 95% confidence interval (CI) 3.70 to 122.96). On completion of the intervention period, disease-specific global HRQoL was significantly better in the intervention group compared to the control group (standardised mean difference (SMD) 0.51; 95% CI 0.08 to 0.93). There was no significant difference between the intervention and control groups in physical functioning HRQoL (SMD 0.11; 95% CI -0.36 to 0.58), dyspnoea (SMD -0.27; 95% CI -0.64 to 0.10), fatigue (SMD 0.03; 95% CI -0.51 to 0.58), feelings of anxiety (MD -1.21 units on Hospital Anxiety and Depression Scale; 95% CI -5.88 to 3.45) and depression (SMD -1.26; 95% CI -4.68 to 2.17), and FEV1 (SMD 0.43; 95% CI -0.11 to 0.97). Exercise training may improve or avoid the decline in exercise capacity and disease-specific global HRQoL for adults with advanced lung cancer. We found no significant effects of exercise training on dyspnoea, fatigue, feelings of anxiety and depression, or lung function. The findings of this review should be viewed with caution because of the heterogeneity between studies, the small sample sizes, and the high risk of bias of included studies. Larger, high-quality RCTs are needed to confirm and expand knowledge on the effects of exercise training in this population. | We looked for all research studies (randomised controlled trials) published up to July 2018. We found six studies which included 221 participants, with an average age ranging from 59 to 70 years. These studies included different numbers of people, ranging from 20 to 111. Our results showed that, compared to those who did not exercise, people with lung cancer who did exercise were fitter and had a better quality of life. We did not find any difference in muscle strength, shortness of breath, tiredness, feelings of anxiety and depression, or lung function. No serious harms were reported in people with lung cancer who exercised, but only three studies talked about harms. The results of this review are not clear, mainly because of the small number of studies found, the small numbers of people in those studies, and because the studies did not seem to have been carried out to a high standard. |
We identified 19 studies, which enrolled 13,216 participants (we included four new studies in this second update). Sixteen out of the 19 studies were eligible for quantitative synthesis. Although the studies varied in setting (general practitioner (GP)-led, nurse-led, or surgeon-led) and 'intensity' of follow-up, there was very little inconsistency in the results. Overall survival: we found intensive follow-up made little or no difference (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.80 to 1.04: I² = 18%; high-quality evidence). There were 1453 deaths among 12,528 participants in 15 studies. In absolute terms, the average effect of intensive follow-up on overall survival was 24 fewer deaths per 1000 patients, but the true effect could lie between 60 fewer to 9 more per 1000 patients. Colorectal cancer-specific survival: we found intensive follow-up probably made little or no difference (HR 0.93, 95% CI 0.81 to 1.07: I² = 0%; moderate-quality evidence). There were 925 colorectal cancer deaths among 11,771 participants enrolled in 11 studies. In absolute terms, the average effect of intensive follow-up on colorectal cancer-specific survival was 15 fewer colorectal cancer-specific survival deaths per 1000 patients, but the true effect could lie between 47 fewer to 12 more per 1000 patients. Relapse-free survival: we found intensive follow-up made little or no difference (HR 1.05, 95% CI 0.92 to 1.21; I² = 41%; high-quality evidence). There were 2254 relapses among 8047 participants enrolled in 16 studies. The average effect of intensive follow-up on relapse-free survival was 17 more relapses per 1000 patients, but the true effect could lie between 30 fewer and 66 more per 1000 patients. Salvage surgery with curative intent: this was more frequent with intensive follow-up (risk ratio (RR) 1.98, 95% CI 1.53 to 2.56; I² = 31%; high-quality evidence). There were 457 episodes of salvage surgery in 5157 participants enrolled in 13 studies. In absolute terms, the effect of intensive follow-up on salvage surgery was 60 more episodes of salvage surgery per 1000 patients, but the true effect could lie between 33 to 96 more episodes per 1000 patients. Interval (symptomatic) recurrences: these were less frequent with intensive follow-up (RR 0.59, 95% CI 0.41 to 0.86; I² = 66%; moderate-quality evidence). There were 376 interval recurrences reported in 3933 participants enrolled in seven studies. Intensive follow-up was associated with fewer interval recurrences (52 fewer per 1000 patients); the true effect is between 18 and 75 fewer per 1000 patients. Intensive follow-up probably makes little or no difference to quality of life, anxiety, or depression (reported in 7 studies; moderate-quality evidence). The data were not available in a form that allowed analysis. Intensive follow-up may increase the complications (perforation or haemorrhage) from colonoscopies (OR 7.30, 95% CI 0.75 to 70.69; 1 study, 326 participants; very low-quality evidence). Two studies reported seven colonoscopic complications in 2292 colonoscopies, three perforations and four gastrointestinal haemorrhages requiring transfusion. We could not combine the data, as they were not reported by study arm in one study. The limited data on costs suggests that the cost of more intensive follow-up may be increased in comparison with less intense follow-up (low-quality evidence). The data were not available in a form that allowed analysis. The results of our review suggest that there is no overall survival benefit for intensifying the follow-up of patients after curative surgery for colorectal cancer. Although more participants were treated with salvage surgery with curative intent in the intensive follow-up groups, this was not associated with improved survival. Harms related to intensive follow-up and salvage therapy were not well reported. | We found 19 studies, including 13,216 participants. Our results are presented along with a judgement of quality which reflects how certain we are about the results. We found that follow-up did not improve overall survival (high-quality evidence), colorectal cancer-specific survival (moderate-quality evidence), or relapse-free survival (high-quality evidence). If patients have follow-up, they are much more likely to have surgery if the cancer is detected again (high-quality evidence). With follow-up, more asymptomatic 'silent' cancer relapses are likely to be found at planned visits (moderate-quality evidence). Harmful side effects (harms) from tests were not common, but more intensive follow-up may increase harms (reported in two studies; very low-quality evidence). Costs may be increased with more intensive follow-up (low-quality evidence). More intensive follow-up probably makes little or no difference for quality of life (moderate-quality evidence). The information we have now suggests that there is little benefit from intensifying follow-up, but there is also little evidence about quality of life, harms, and costs. We do not know what is the best way to follow patients treated for non-metastatic (no secondaries) colorectal cancer, or if we should at all. We know little about the costs of follow-up in this setting. Consumer needs and concerns with respect to the value of follow-up require further research. |
Eleven trials involving 2487 participants were included. The quality of the nine trials which predated routine computerised tomography (CT) scanning and the use of the International Normalised Ratio to monitor anticoagulation was poor. There was no evidence of an effect of anticoagulant therapy on either the odds of death or dependency (two trials, odds ratio (OR) 0.83, 95% confidence interval (CI) 0.52 to 1.34) or of 'non-fatal stroke, myocardial infarction, or vascular death' (four trials, OR 0.96, 95% CI 0.68 to 1.37). Death from any cause (OR 0.95, 95% CI 0.73 to 1.24) and death from vascular causes (OR 0.86, 95% CI 0.66 to 1.13) were not significantly different between treatment and control. The inclusion of two recently completed trials did not alter these conclusions. There was no evidence of an effect of anticoagulant therapy on the risk of recurrent ischaemic stroke (OR 0.85, 95% CI 0.66 to 1.09). However, anticoagulants increased fatal intracranial haemorrhage (OR 2.54, 95% CI 1.19 to 5.45), and major extracranial haemorrhage (OR 3.43, 95% CI 1.94 to 6.08). This is equivalent to anticoagulant therapy causing about 11 additional fatal intracranial haemorrhages and 25 additional major extracranial haemorrhages per year for every 1000 patients given anticoagulant therapy. Compared with control, there was no evidence of benefit from long-term anticoagulant therapy in people with presumed non-cardioembolic ischaemic stroke or transient ischaemic attack, but there was a significant bleeding risk. | In patients with an irregular heart rhythm (atrial fibrillation), anticoagulant drugs, such as warfarin, prevent such clots forming and prevent stroke. However, anticoagulant drugs may also cause bleeding in the brain and this harmful effect could outweigh any benefits in patients with a normal heart rhythm. This review identified 11 trials, involving 2487 participants who had had a stroke (and also had a normal heart rhythm), of anticoagulants to prevent further strokes. There was good evidence that anticoagulants could cause serious bleeding, and there was no evidence that, in such patients, anticoagulants were of benefit in the prevention of further strokes. Other trials have shown that, in a person with a normal heart rhythm who has had an ischaemic stroke, antiplatelet drugs such as aspirin are a safe and effective way to reduce the risk of further strokes and heart attacks. |
The original version of this Cochrane review included five RCTs involving 1277 women. In this 2015 update, no new studies met the inclusion criteria but we included an additional paper with mature data (10-year follow-up) relating to a previously included study (ICON1). We included four studies in the meta-analyses and considered them to be at a low risk of bias. Most study participants (> 95%) had stage I ovarian cancer. Meta-analysis of five-year data from three studies indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (Hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53 to 0.93; 1008 women; 3 studies; I² statistic = 0%; high quality evidence). Likewise, meta-analysis of five-year data from four studies indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (HR 0.67, 95% CI 0.53 to 0.84; 1170 women, 4 studies; I² statistic = 0%; high quality evidence). These findings were robust over time, with 10-year HR estimates of 0.72 (95% CI 0.57 to 0.92; 925 women, 2 studies) and 0.67 (95% CI 0.53 to 0.83; 925 women, 2 studies) for OS and PFS, respectively (high quality evidence). The risk of death at 10 years follow-up favoured the adjuvant chemotherapy arm (0.76, 95% CI 0.62 to 0.94; 923 women, 2 studies; I² statistic = 0%), as did the findings for risk of progression at 10 years (RR 0.72, 95% CI 0.60 to 0.87; 925 women, 2 studies; I² statistic = 0%). Low quality evidence suggested that women with high-risk disease may have the most to gain from adjuvant chemotherapy. However, subgroup analyses could neither confirm nor exclude survival benefits in lower risk disease or in optimally staged disease. We found insufficient data to compare adverse events and long term risks between chemotherapy and observation groups. High-quality evidence indicates that adjuvant platinum-based chemotherapy is effective in prolonging survival in women with early stage (FIGO stage I/IIa) epithelial ovarian cancer. It remains uncertain whether women with low- and intermediate-risk early stage disease will benefit as much from adjuvant chemotherapy as women with high-risk disease. Decisions to use adjuvant chemotherapy (AC) in these women should be mindful of this uncertainty, and the uncertainty regarding adverse events. Treatment of women with lower risk disease should be individualised to take into account individual factors. | We searched the literature up to 24th March 2015 and included five trials involving 1277 women with early-stage OC in the review, and four good quality trials contributed data. Most women (more than 95%) had stage I OC. For this update, we identified one additional publication of 10-year follow-up results from a trial already included in the review, but found no new trials. We found high quality evidence that women diagnosed with early-stage OC who received AC after surgery to remove and stage the disease had a lower risk of dying within 10 years than women who did not receive AC (observation group), and a lower risk of the cancer returning in the 10 years after treatment (see Cates plot, Figures 4 to 7). Low quality evidence suggested that women with higher risk disease may have more to gain from AC, but we could not exclude a survival benefit for other early stage disease. Chemotherapy can have side effects but we found insufficient data to compare adverse events and long term risks between chemotherapy and observation groups. In early stage ovarian cancer, AC improves survival and reduces the risk of ovarian cancer recurring compared with no AC. Therefore AC in early stage disease should be considered in all women. However, it remains uncertain whether women with lower risk early stage disease will benefit much from AC and decisions to use AC should be mindful of this uncertainty, and the uncertainty regarding adverse events. |
We included ten RCTs with varying risk of bias. For patients with acute LBP, results from two trials (N = 401) suggest small improvements in pain relief (SMD 0.22 (95% CI: 0.02 to 0.41) and functional status (SMD 0.29 (95% CI: 0.09 to 0.49) in favour of advice to stay active. For patients with sciatica, there is moderate quality evidence of little or no difference in pain relief (SMD -0.03 (95% CI: -0.24 to 0.18)) or functional status (SMD 0.19 (95% CI: -0.02 to 0.41)), between advice to rest in bed or stay active. Low quality evidence (3 RCTs, N = 931) suggests little or no difference between exercises, advice to rest in bed or stay active for patients with acute LBP. Low quality evidence (1 RCT, N = 250) suggests little or no difference between physiotherapy, advice to rest in bed or stay active for patients with sciatica. No trials that compared different ways of delivering advice. Moderate quality evidence shows that patients with acute LBP may experience small benefits in pain relief and functional improvement from advice to stay active compared to advice to rest in bed; patients with sciatica experience little or no difference between the two approaches. Low quality evidence suggests little or no difference between those who received advice to stay active, exercises or physiotherapy. Further research is very likely to have an important impact on the estimate of effect and is likely to change our confidence in it. | This blended, updated review included 10 randomised trials (N = 1923). It evaluated the effects of advice to rest in bed or stay active on individuals with acute low-back pain (pain lasting for less than 6 weeks) with or without sciatica. Moderate quality evidence shows that patients with acute LBP may experience small improvements in pain relief and ability to perform everyday activities if they receive advice to stay active compared to advice to rest in bed. However, patients with sciatica experience little or no difference between the two approaches. Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality evidence suggests those patients with or without sciatica experienced little or no difference in pain relief or function, regardless of whether they received advice to stay active, exercises or physiotherapy. Further research is very likely to have an important impact on the estimate of effect and is likely to change our confidence in it. |
We included four randomized studies (duration 7 to 15 months) involving 116 males. Risk of bias was judged to be high in two studies due to the open-label study design and in one study due to attrition bias. Two studies compared on-demand treatment to prophylaxis with bypassing agents. In one study (34 males) prophylaxis significantly reduced mean overall bleeding rates, MD - 7.27 (95% CI -9.92 to -4.62) (low quality evidence), mean number of overall bleeding events per month, MD -1.10 (95% CI -1.54 to -0.66), mean number of hemarthrosis, MD -6.60 (95% CI -9.32 to -3.88) (low quality evidence) and mean number of joints that had hemarthrosis, MD -0.90 (95% CI -1.36 to -0.44). The meta-analysis did not conclusively demonstrate significant benefit of prophylaxis on health-related quality of life as measured by Haem-A-QoL score, EQ-5D total score and utility score, EQ-5D VAS and SF-36 physical summary and mental summary score (low quality evidence for all health-related quality of life analyses). The remaining two studies compared dose regimens. The results from one study (22 males) did not conclusively demonstrate benefit or harm of high-dose versus low-dose recombinant activated factor VIIa (rFVIIa) as a prophylaxis for overall bleeding rate, MD -0.82 (95% CI -2.27 to 0.63) (moderate quality evidence), target joint bleeding rate, MD -3.20 (95% CI -7.23 to 0.83) (moderate quality evidence) and serious adverse events, RR 9.00 (95% CI, 0.54 to 149.50) (moderate quality evidence). The overall quality of evidence was moderate to low due to imprecision from limited information provided by studies with small sample sizes and incomplete outcome data in one study. The evidence suggests that prophylaxis with bypassing agents may be effective in reducing bleeding in males with hemophilia with inhibitors. However, there is a lack of evidence for the superiority of one agent over the other or for the optimum dosage regimen. Further studies are needed to evaluate the benefits and harms of prophylaxis treatment on health-related quality of life, as well as the effects of dose of bypassing agents on the outcomes. | We searched the scientific databases for clinical studies evaluating the effects of bypassing agents in men with hemophilia A or B with inhibitors. We included four studies (duration 7 to 15 months), involving 116 individuals. Two studies compared the prophylactic infusion with bypassing agent to on-demand treatment (treatment given only after the bleeding occurred) and two studies compared high-dose to low-dose preventative therapies. Limited evidence showed that prophylactic use of bypassing agents reduced bleeding events, joint bleeding events and number of affected joints. There was no evidence for improved quality of life amongst those who received prophylaxis as compared to those who received on-demand therapy. There was no evidence for a difference in benefits or harms between high- and low-dose rFVIIa for prophylaxis. The overall quality of evidence of these studies was moderate to low as the included studies were small and provided limited information. Also, in one of the studies, up to 24% of the men recruited were not included in the analysis of the results, which further increases imprecision of results. |
25 studies were included: 2 RCTs, 1 cohort study, 6 case-control studies and 16 cross-sectional surveys. Only one RCT was judged to be at low risk of bias. The other RCT and all observational studies were judged to be at moderate to high risk of bias. Studies were included in four intervention/exposure comparisons. A statistically significant reduction in fluorosis was found if brushing of a child's teeth with fluoride toothpaste commenced after the age of 12 months odds ratio 0.70 (random-effects: 95% confidence interval 0.57 to 0.88) (data from observational studies). Inconsistent statistically significant associations were found between starting using fluoride toothpaste/toothbrushing before or after the age of 24 months and fluorosis (data from observational studies). From the RCTs, use of higher level of fluoride was associated with an increased risk of fluorosis. No significant association between the frequency of toothbrushing or the amount of fluoride toothpaste used and fluorosis was found. There should be a balanced consideration between the benefits of topical fluorides in caries prevention and the risk of the development of fluorosis. Most of the available evidence focuses on mild fluorosis. There is weak unreliable evidence that starting the use of fluoride toothpaste in children under 12 months of age may be associated with an increased risk of fluorosis. The evidence for its use between the age of 12 and 24 months is equivocal. If the risk of fluorosis is of concern, the fluoride level of toothpaste for young children (under 6 years of age) is recommended to be lower than 1000 parts per million (ppm). More evidence with low risk of bias is needed. Future trials assessing the effectiveness of different types of topical fluorides (including toothpastes, gels, varnishes and mouthrinses) or different concentrations or both should ensure that they include an adequate follow-up period in order to collect data on potential fluorosis. As it is unethical to propose RCTs to assess fluorosis itself, it is acknowledged that further observational studies will be undertaken in this area. However, attention needs to be given to the choice of study design, bearing in mind that prospective, controlled studies will be less susceptible to bias than retrospective and/or uncontrolled studies. | The aim of this review was to evaluate whether the use of fluoride toothpaste by children is associated with an increased risk of developing dental fluorosis in children. The review included 25 studies of different designs; some providing stronger evidence than others. There is some evidence that brushing a child's teeth with a toothpaste containing fluoride, before the age of 12 months, may be associated with an increased risk of developing fluorosis. There is stronger evidence that higher levels of fluoride (1000 parts per million (ppm) or more) in toothpaste are associated with an increased risk of fluorosis when given to children under 5 to 6 years of age. However, for some children (those considered to be at high risk of tooth decay by their dentist), the benefit to health of preventing decay may outweigh the risk of fluorosis. In such circumstances, careful brushing by parents/adults with toothpastes containing higher levels of fluoride would be beneficial. |
Seven randomised, controlled trials encompassing 842 patients undergoing SGIA versus DGIA were retrieved from the electronic databases. There were 408 patients in the SGIA group and 432 patients in the DGIA group. All included studies were small, with sample sizes ranging from 60 to 172. There was no heterogeneity among the included trials. Therefore, in the fixed effects model, incidence of anastomotic dehiscence, peri-operative complications and mortality was statistically equivalent between two techniques of GIA. Average hospital stay following SGIA and DGIA was also comparable. However, SGIA was superior in terms of shorter operative time. Sensitivity analysis of relatively good quality and poor quality trials supported same conclusion. SGIA can be performed quicker as compared to double layer GIA. SGIA is comparable to DGIA in terms of anastomotic leak, peri-operative complications, mortality and hospital stay. SGIA may routinely be used for GIA following bowel resection. However, since this conclusion is derived from smaller number of patients recruited in relatively moderate quality trials, further trials should be aimed to reduce the limitations of this review. | This review concludes that single layer anastomosis is comparable to double layer anastomosis in terms of anastomotic leak, peri-operative complications, death rate and hospital stay. Single layer anastomosis consumes shorter operative time as compared to double layer. Therefore, single layer anastomosis may routinely be used for the anastomosis of gastrointestinal tract following bowel resection. However, since this conclusion is derived from smaller number of patients recruited in relatively moderate quality trials, further trials should be aimed to reduce the limitations of this review. |
Two small randomised controlled trials were located, one with higher dose NaHCO3 and alternating allocation, the other with lower dose NaHCO3 was presented in abstract form only. In the higher dose study, the RR of death in patients receiving NaHCO3 compared to controls was 0.52 (95% CI 0.05 to 5.39) and the WMD for total dose of atropine was -36.1 (95% CI -68.43 to -3.77). No clinical benefits from lower dose NaHCO3 were noted. Six other studies were identified but none satisfied inclusion criteria; three studies were uncontrolled and three were controlled. NaHCO3 was used in each study to induce alkalinisation. Marked heterogeneity between subjects and treatments was noted - for example, varying regimens of NaHCO3. Preliminary studies suggest benefit from blood alkalinisation with NaHCO3 in OP poisoning, but there is insufficient evidence to support its routine clinical use. Further research is required to determine the method of alkalinisation that will optimise outcomes, and the regimen which will produce the target arterial pH of 7.50 (range 7.45 to 7.55). This should be followed by a well-designed randomised controlled trial to determine efficacy. | The review authors looked for studies in which such chemicals were given to OP poisoned patients, to see how effective the treatment is. They sought randomised controlled trials, a type of research study in which one group of patients is given one treatment, while a similar group (the control group) is given a different treatment. The authors found eight studies but only two small randomised controlled trials, one using higher dose sodium bicarbonate and the other a lower dose. Only the trial using higher dose sodium bicarbonate, which included 53 participants, showed a slight benefit from using sodium bicarbonate in conjunction with standard treatment for OP poisoning. This study does not provide enough evidence to recommend routine clinical use of sodium bicarbonate. There are hundreds of different kinds of OPs so treatment may vary based on the type of poisoning as well as the severity of the poisoning. More research needs to be done to determine the best treatment for poisoning with OPs in various situations. |
A total of 21 eligible RCTs were identified and used for meta-analysis purposes. Overall, 16,215 patients with colorectal cancer were enrolled, 9,785 being affected with rectal carcinoma. Considering patients with rectal cancer only, 4,854 cases were randomized to receive potentially curative surgery of the primary tumour plus adjuvant chemotherapy and 4,367 to receive surgery plus observation. The mean number of patients enrolled was 466 (range: 54-1,243 cases). 11 RCTs had been performed in Western countries and 10 in Japan. All trials used fluoropyrimidine-based chemotherapy (no modern drugs - such as oxaliplatin, irinotecan or biological agents - were tested). Overall survival (OS) data were available in 21 RCTs and the data available for meta-analysis regarded 9,221 patients: of these, 4854 patients were randomized to adjuvant chemotherapy (treatment arm) and 4,367 patients did not receive adjuvant chemotherapy (control arm). The meta-analysis of these RCTs showed a significant reduction in the risk of death (17%) among patients undergoing postoperative chemotherapy as compared to those undergoing observation (HR=0.83, CI: 0.76-0.91). Between-study heterogeneity was moderate (I-squared=30%) but significant (P=0.09) at the 10% alpha level. Disease-free survival (DFS) data were reported in 20 RCTs, and the data suitable for meta-analysis included 8,530 patients. Of these, 4,515 patients were randomized to postoperative chemotherapy (treatment arm) and 4,015 patients received no postoperative chemotherapy (control arm). The meta-analysis of these RCTs showed a reduction in the risk of disease recurrence (25%) among patients undergoing adjuvant chemotherapy as compared to those undergoing observation (HR=0.75, CI: 0.68-0.83). Between-study heterogeneity was moderate (I-squared=41%) but significant (P=0.03). While analyzing both OS and DFS data, sensitivity analyses did not find any difference in treatment effect based on trial sample size or geographical region (Western vs Japanese). Available data were insufficient to investigate on the effect of adjuvant chemotherapy separately in different TNM stages in terms of both OS and DFS. No plausible source of heterogeneity was formally identified, although variability in treatment regimens and TNM stages of enrolled patients might have played a significant role in the difference of reported results. The results of this meta-analysis support the use of 5-FU based postoperative adjuvant chemotherapy for patients undergoing apparently radical surgery for non-metastatic rectal carcinoma. Available data do not allow us to define whether the efficacy of this treatment is highest in one specific TNM stage. The implementation of modern anti-cancer agents in the adjuvant setting is warranted to improve the results shown by this meta-analysis. Randomized trials of adjuvant chemotherapy for patients receiving preoperative neoadjuvant therapy are also needed in order to define the role of postoperative chemotherapy in the multimodal treatment of resectable rectal cancer. | This systematic review and meta-analysis, which is the first in this field, shows a significant beneficial effect on both overall (OS) and disease-free survival (DFS) for patients undergoing postoperative chemotherapy after removal of their primary rectal tumour. Further investigation is needed to define the role of postoperative chemotherapy in the multimodal treatment of patients with rectal carcinoma: for instance, modern anti-cancer agents (including so called "smart drugs") and integration with neoadjuvant therapy (such as preoperative chemoradiation) should be taken into consideration in order to improve the encouraging findings of this meta-analysis. |
In this updated version of the review, we found no new studies that met our inclusion criteria. We included in this review four studies that compared neuraxial anaesthesia with general anaesthesia. The total number of participants was 696, of whom 417 were allocated to neuraxial anaesthesia and 279 to general anaesthesia. Participants allocated to neuraxial anaesthesia had a mean age of 67 years, and 59% were men. Participants allocated to general anaesthesia had a mean age of 67 years, and 66% were men. Four studies had an unclear risk of bias. No difference was observed between participants allocated to neuraxial or general anaesthesia in mortality rate (OR 0.89, 95% CI 0.38 to 2.07; 696 participants; four trials), myocardial infarction (OR 1.23, 95% CI 0.56 to 2.70; 696 participants; four trials), and lower-limb amputation (OR 0.84, 95% CI 0.38 to 1.84; 465 participants; three trials). Pneumonia was less common after neuraxial anaesthesia than after general anaesthesia (OR 0.37, 95% CI 0.15 to 0.89; 201 participants; two trials). Evidence was insufficient for cerebral stroke, duration of hospital stay, postoperative cognitive dysfunction, complications in the anaesthetic recovery room and transfusion requirements. No data described nerve dysfunction, postoperative wound infection, patient satisfaction, postoperative pain score, claudication distance and pain at rest. Available evidence from included trials that compared neuraxial anaesthesia with general anaesthesia was insufficient to rule out clinically important differences for most clinical outcomes. Neuraxial anaesthesia may reduce pneumonia. No conclusions can be drawn with regard to mortality, myocardial infarction and rate of lower-limb amputation, or less common outcomes. | This systematic review is important because review authors assessed the risk of important outcomes after lower-limb revascularization with the participant under neuraxial or general anaesthesia. They performed this systematic review to answer a single research question: What are the rates of death and major complications with spinal and epidural anaesthesia as compared with other types of anaesthesia for lower-limb revascularization? In this second update of the Cochrane review, we searched the databases until April 2013 but found no new studies. The total number of participants in the four included studies was 696, of whom 417 received neuraxial anaesthesia and 279 received general anaesthesia. No evidence revealed differences in postoperative risk of death, myocardial infarction or leg amputation between the two types of anaesthetic. The risk of pneumonia was 9% after neuraxial anaesthesia and 20% after general anaesthesia. Evidence was insufficient to show the effects of neuraxial anaesthesia compared with other types of anaesthesia on cerebral stroke, duration of hospital stay, postoperative cognitive dysfunction, complications in the anaesthetic recovery room and transfusion requirements. No data described nerve dysfunction, postoperative wound infection, patient satisfaction, postoperative pain score, claudication distance and pain at rest. One study recruited more than 50% of all reported cases.This systematic review shows that neuraxial anaesthesia may reduce the risk of pneumonia after lower-limb revascularization, but evidence is insufficient to support other benefits or harms. |
We included only one small pilot study (involving 30 women). The study, which we considered to be at low risk of bias, was conducted in a tertiary referral hospital in Australia, and involved women with cephalic, singleton pregnancies. The primary outcome was operative delivery (instrumental delivery or caesarean section). In the manual rotation group, 13/15 women went on to have an instrumental delivery or caesarean section, whereas in the control group, 12/15 women had an operative delivery. The estimated risk ratio was 1.08 (95% confidence interval 0.79 to 1.49). There were no maternal or fetal mortalities in either group There were no clear differences for any of the secondary maternal or neonatal outcomes reported (e.g. perineal trauma, analgesia use duration of labour). In terms of adverse events, there were no reported cases of umbilical cord prolapse or cervical laceration and a single case of a non-reassuring or pathological cardiotocograph during the procedure. Currently, there is insufficient evidence to determine the efficacy of prophylactic manual rotation early in the second stage of labour for prevention of operative delivery. One additional study is ongoing. Further appropriately designed trials are required to determine the efficacy of manual rotation. | We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and other databases for clinical trials comparing manual rotation with expectant management (waiting), speeding up of labour or operation. The women were at term (at least 37 weeks of pregnancy). The results are current to October 2014. We found only one small pilot trial involving 30 women that assessed the feasibility of manual rotation versus routine care (no manual rotation). The study reported no clear difference for the review's primary outcomes of operative delivery (vacuum-assisted delivery or forceps delivery (or both), or caesarean section) and no mother or baby deaths. In terms of adverse events, there were no reported cases of umbilical cord prolapse or cervical laceration and a single case of a non-reassuring or pathological cardiotocograph during the procedure. Further research is needed to assess the effect of manual rotation in second stage of labour to reduce operative delivery rates. We considered the study at low risk of bias but it did not have sufficient participants to detect important clinical benefits or harms of manual rotation to correct the baby's position in second stage of labour. |
Eleven trials were selected for inclusion in the review, including a total of 776 men. They were generally small; all were of poor quality and all were deemed to have high risk of bias. Performing intermittent self-dilatationversus not performing intermittent self-dilatation The data from six trials were heterogeneous, imprecise and had a high risk of bias, but indicated that recurrent urethral stricture was less likely in men who performed intermittent self-dilatation than men who did not perform intermittent self-dilatation (RR 0.70, 95% CI 0.48 to 1.00; very low quality evidence). Adverse events were generally poorly reported: two trials did not report adverse events and two trials reported adverse events only for the intervention group. Meta-analysis of the remaining two trials found no evidence of a difference between performing intermittent self-dilatation and not performing it (RR 0.60, 95% CI 0.11 to 3.26). No trials formally assessed acceptability, and no trials reported on patient-reported lower urinary tract symptoms, patient-reported health-related quality of life, or cost-effectiveness. One programme of intermittent self-dilatationversus another We identified two trials that compared different durations of intermittent self-dilatation, but data were not combined. One study could not draw robust conclusions owing to cross-over, protocol deviation, administrative error, post-hoc analysis and incomplete outcome reporting. The other study found no evidence of a difference between intermittent self-dilatation for six months versus for 12 months after optical urethrotomy (RR 0.67, 95% CI 0.12 to 3.64), although again the evidence is limited by the small sample size and risk of bias in the included study. Adverse events were reported narratively and were not stratified by group. No trials formally assessed acceptability, and no trials reported on patient-reported lower urinary tract symptoms, patient-reported health-related quality of life, or cost-effectiveness. One device for performing intermittent self-dilatationversus another Three trials compared one device for performing intermittent self-dilatation with another. Results from one trial at a high risk of bias were too uncertain to determine the effects of a low friction hydrophilic catheter and a standard polyvinyl chloride catheter on the risk of recurrent urethral stricture (RR 0.32, 95% CI 0.07 to 1.40). Similarly one study did not find evidence of a difference between one percent triamcinolone gel for lubricating the intermittent self-dilatation catheter versus water-based gel on risk of recurrent urethral stricture (RR 0.68, 95% CI 0.35 to 1.32). Two trials reported adverse events, but one did not provide sufficient detail for analysis. The other small study reported fewer instances of prostatitis, urethral bleeding or bacteriuria with a low friction hydrophilic catheter compared with a standard polyvinyl chloride catheter (RR 0.13, 95% CI 0.02 to 0.98). ‘Happiness with the intervention’ was assessed using a non-validated scale in one study, but no trials formally assessed patient-reported health-related quality of life or acceptability. No trials reported on patient-reported lower urinary tract symptoms or cost-effectiveness. GRADE quality assessment The evidence that intermittent self-dilatation reduces the risk of recurrent urethral stricture after surgical intervention was downgraded to 'very low' on the basis that the studies comprising the meta-analysis were deemed to have high risk of bias, and the data was imprecise and inconsistent. Insufficient evidence No trials provided cost-effectiveness data or used a validated patient-reported outcome measure, and adverse events were not reported rigorously. Acceptability of the intervention to patients has not been assessed quantitatively or qualitatively. Performing intermittent self-dilatation may confer a reduced risk of recurrent urethral stricture after endoscopic treatment. We have very little confidence in the estimate of the effect owing to the very low quality of the evidence. Evidence for other comparisons and outcomes is limited. Further research is required to determine whether the apparent benefit is sufficient to make the intervention worthwhile, and in whom. | We found 11 trials involving a total of 776 men across eight countries for this review. A combination of results from six trials involving a total of 404 participants indicated that men with urethral stricture who perform intermittent self-dilatation may have less chance of their urethral stricture coming back than men with a urethral stricture who do not perform intermittent self-dilatation. We can not be confident about this finding, however, because the quality of the evidence was very low. There were no trials that looked at whether intermittent self-dilatation is a cost-effective health care intervention and there were no trials that used reliable health questionnaires to find out whether intermittent self-dilatation reduces men's urinary symptoms or improves their overall well being. On the whole the trials did not report side effects in a way that was useful for estimating the risks of performing intermittent self-dilatation. We do not know yet whether certain types of catheter are better than others for performing intermittent self-dilatation. It is also unclear how often or for how long men should perform intermittent self-dilatation to give themselves the best chance of staying free from urethral strictures. The trials in this review were generally small and poorly designed or poorly explained. All of the trials were conducted in a way which meant they had a high chance of generating an answer that does not represent the truth. |
We included 38 unique studies with 3290 men with CP/CPPS across 23 comparisons. 1. Acupuncture: (three studies, 204 participants) based on short-term follow-up, acupuncture probably leads to clinically meaningful reduction in prostatitis symptoms compared with sham procedure (mean difference (MD) in total NIH-CPSI score -5.79, 95% confidence interval (CI) -7.32 to -4.26, high QoE). Acupuncture may result in little to no difference in adverse events (low QoE). Acupuncture may not reduce sexual dysfunction when compared with sham procedure (MD in the International Index of Erectile Function (IIEF) Scale -0.50, 95% CI -3.46 to 2.46, low QoE). Acupuncture may also lead to a clinically meaningful reduction in prostatitis symptoms compared with standard medical therapy (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, low QoE). We found no information regarding quality of life, depression or anxiety. 2. Lifestyle modifications: (one study, 100 participants) based on short-term follow-up, lifestyle modifications may be associated with a reduction in prostatitis symptoms compared with control (risk ratio (RR) for improvement in NIH-CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE). We found no information regarding adverse events, sexual dysfunction, quality of life, depression or anxiety. 3. Physical activity: (one study, 85 participants) based on short-term follow-up, a physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69 to -0.31, low QoE). This programme may not reduce anxiety or depression (low QoE). We found no information regarding adverse events, sexual dysfunction or quality of life. 4. Prostatic massage: (two studies, 115 participants) based on short-term follow-up, we are uncertain whether the prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE). We found no information regarding adverse events, sexual dysfunction, quality of life, depression or anxiety. 5. Extracorporeal shockwave therapy: (three studies, 157 participants) based on short-term follow-up, extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46 to -4.89, high QoE). These results may not be sustained at medium-term follow-up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE). This treatment probably improves sexual dysfunction (MD in the IIEF Scale MD 3.34, 95% CI 2.68 to 4.00, one study, 60 participants, moderate QoE). We found no information regarding quality of life, depression or anxiety. 6. Transrectal thermotherapy compared to medical therapy: (two studies, 237 participants) based on short-term follow-up, transrectal thermotherapy alone or in combination with medical therapy may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study reported that participants may experience transient adverse events. We found no information regarding sexual dysfunction, quality of life, depression or anxiety. 7. Other interventions: there is uncertainty about the effects of most of the other interventions included in this review. We found no information regarding psychological support or prostatic surgery. Based on the findings of moderate quality evidence, this review found that some non-pharmacological interventions such as acupuncture and extracorporeal shockwave therapy are likely to result in a decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse event. The QoE for most other comparisons was predominantly low. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes. | The evidence was current to August 2017. We found 38 studies that were conducted between 1993 and 2016 with 3187 participants that made 23 comparisons between different treatments in men with CP/CPPS. The evaluated interventions usually implied the use of devices, medical advice or some form of physical therapy. In many cases, these therapies were given to men in an outpatient setting. Most studies did not specify their funding sources; three studies reported funding from device makers. Acupuncture: we found that acupuncture (an alternative medicine where thin needles are inserted into the skin at specific points) probably causes a significant decrease in symptoms of prostatitis and may not associated with side effects when compared with pretend acupuncture, however, it may not reduce sexual problems. It probably decreases symptoms when compared with standard medical therapy. We found no information on its effect on quality of life, depression or anxiety. Lifestyle modifications: we are uncertain whether the recommendation of lifestyle modifications reduces symptoms when compared to the continuation of the same lifestyle. We had no information regarding side effects, sexual problems, quality of life, depression or anxiety. Physical activity: we found that a physical activity programme may reduce symptoms (small effect) when compared with a non-specific activity used as a control, however it may not reduce anxiety or depression. We have no information regarding side effects, sexual problems or quality of life. Prostatic massage: we are uncertain whether the prostatic massage reduces or increases symptoms when compared with no massage. We found no information regarding side effects, sexual problems, quality of life, depression or anxiety. Extracorporeal shockwave therapy: we found that extracorporeal shockwave therapy (where shock waves are passed through the skin to the prostate) causes a significant decrease in symptoms compared to a simulated procedure. These results may not be lasting after more continued treatment. This treatment may not be associated with side effects. We have no information regarding quality of life, depression or anxiety. Transrectal thermotherapy compared to medical therapy: we found that transrectal thermotherapy (which applies heat to the prostate and pelvic muscle area) alone or in combination with medical therapy may cause a small decrease in symptoms compared to medical therapy alone. One of the included studies reported that participants may experience transient side effects. We have no information regarding sexual problems, quality of life, depression or anxiety. There is uncertainty about the effects of other interventions. The quality of the evidence was low in most cases, meaning that there is much uncertainty surrounding the results. The included studies were not well designed, had a small sample size and had a short follow-up time (usually 12 weeks). |
The searches identified 7558 titles, and we excluded 7513 during title and abstract searches. We reviewed 45 papers in full, and excluded 39. We identified four studies on handsearching of the references, which, along with the six eligible papers from the database search, led to 10 studies being included. Four studies, three of which were RCTs and one prospective study, investigated the effect of elemental diet on GI symptoms; one RCT investigated the effect of dietary modification and elemental diet; and five RCTs investigated dietary modification. Studies were varied in terms of risk of bias. Data were dichotomised for presence and absence of diarrhoea at the end of radiotherapy for four trials evaluating dietary modification comprising modified fat, lactose, fibre or combinations of these dietary changes. A reduction in diarrhoea was demonstrated with nutritional intervention (risk ratio (RR) 0.66; 95% confidence interval (CI) 0.51 to 0.87, four studies, 413 participants, moderate quality of evidence) with low heterogeneity (Chi2 = 3.50, I2 = 14%). Two trials evaluating dietary modification on weight change (comparing baseline and end of radiotherapy) showed no difference between intervention or control (mean difference (MD) -0.57 kg; 95% CI -1.22 to 0.09) with low heterogeneity (Chi2 = 1.41, I2 = 29%). Generally adverse effects were poorly reported in included studies. Elemental diet in particular was poorly tolerated. GI symptoms or toxicity > 6 months after radiotherapy was not reported in included studies There have been benefits demonstrated with dietary modification during pelvic radiotherapy to reduce diarrhoea. Those diets included single interventions or combinations of modified fat, lactose-restriction, fat-restriction and fibre supplementation. We were unable to meta-analyse elemental diet, as data were not available. We considered some of the studies to be at high risk of bias. There have been recent advances in novel, more targeted radiotherapy techniques, such that the findings of older studies need to be interpreted with caution. In addition, there were problems with compliance and palatability with some of the interventions, particularly elemental diet, which limits its usefulness in clinical practice. | Searches of all relevant sources of medical information identified 7558 articles, and, after initial screening of all these articles, we selected 45 as being suitable for this review. On reading the summaries of these 45 trials, 10 were suitable to be included in this review. We included trials that looked at the effects of a nutritional intervention in adults aged 18 years or over having radical pelvic radiotherapy as part of anticancer treatment for a primary pelvic cancer. We excluded patients with stomas and a previous history of inflammatory bowel disease. Results showed that studies evaluating dietary changes, including changes in dietary fat, fibre and lactose, during radiotherapy reduced diarrhoea at the end of treatment. However, these dietary changes did not seem to improve patients' weights. While some changes to diet during radiotherapy may benefit patients by reducing diarrhoea, it is important to recognise that some of the studies reviewed were dated and there have been changes in radiotherapy technique since then that may give patients less diarrhoea anyway. In addition, many studies were of poor quality and, therefore, only a small number were able to be included in this review. Some interventions described, for example, having to take a liquid diet, were not acceptable as many patients found them difficult to tolerate and were unable to take them completely. |
A single study of 21 patients compared SIRT and systemic chemotherapy (fluorouracil and leucovorin) with chemotherapy alone. There was a significant improvement in progression free survival and median survival associated with SIRT, both for the total studied population and for those disease limited to the liver. There was an increase in toxicity with the use of SIRT. A second study of 63 eligible patients compared SIRT and regional chemotherapy (floxuridine) with regional chemotherapy alone. There was no significant difference in progression free survival and median survival seen with SIRT, in either the total patient group or in the 22 patients with disease limited to the liver. There was no significant increase in toxicity with the addition of SIRT to regional chemotherapy. There were no randomised studies comparing SIRT with best supportive care in patients with refractory disease, and no randomised studies assessing the effect of SIRT in patients with resectable liver metastases. There is a need for well designed, adequately powered phase III trials assessing the effect of SIRT when used with modern combination chemotherapy regimens. Further studies are also needed for patients with refractory disease with a particular focus on the impact on quality of life. | In one study that had 21 participants, radioactive beads (injected into the blood vessels of the liver) given with chemotherapy (into the veins of the arm) was more effective at controlling the cancer and improving how long people lived than chemotherapy given on it's own. However, in this study more people who received the radioactive beads suffered from side effects and this study used an older type of chemotherapy that is less effective than the newer treatments that are now available. In a second study with 63 participants, radioactive beads were given with chemotherapy that was injected directly into the blood vessels of the liver. In this study there was no extra benefit in the control of cancer growth or survival for those participants who received radioactive beads in addition to the chemotherapy. More studies are needed with a particular focus on whether radioactive beads provides extra benefit when given with newer chemotherapy treatments, and if radioactive beads provide benefit when given on their own. |
We retrieved 24,310 citations after removal of duplicates. We reviewed the full text of 317 full-text articles and finally included 70 records, referring to 48 studies, in our synthesis. We were able to perform meta-analysis on 28 studies in the community setting (44 articles) and on 6 studies in primary care (8 articles), but we could not extract usable 2 x 2 data for the remaining 14 community studies, which we did not include in the meta-analysis. All of the studies in the community were in asymptomatic people, whereas two of the six studies in primary care were conducted in people who had symptoms of possible dementia. We judged two studies to be at high risk of bias in the patient selection domain, three studies to be at high risk of bias in the index test domain and nine studies to be at high risk of bias regarding flow and timing. We assessed most studies as being applicable to the review question though we had concerns about selection of participants in six studies and target condition in one study. The accuracy of the MMSE for diagnosing dementia was reported at 18 cut points in the community (MMSE score 10, 14-30 inclusive) and 10 cut points in primary care (MMSE score 17-26 inclusive). The total number of participants in studies included in the meta-analyses ranged from 37 to 2727, median 314 (interquartile range (IQR) 160 to 647). In the community, the pooled accuracy at a cut point of 24 (15 studies) was sensitivity 0.85 (95% confidence interval (CI) 0.74 to 0.92), specificity 0.90 (95% CI 0.82 to 0.95); at a cut point of 25 (10 studies), sensitivity 0.87 (95% CI 0.78 to 0.93), specificity 0.82 (95% CI 0.65 to 0.92); and in seven studies that adjusted accuracy estimates for level of education, sensitivity 0.97 (95% CI 0.83 to 1.00), specificity 0.70 (95% CI 0.50 to 0.85). There was insufficient data to evaluate the accuracy of the MMSE for diagnosing dementia subtypes.We could not estimate summary diagnostic accuracy in primary care due to insufficient data. The MMSE contributes to a diagnosis of dementia in low prevalence settings, but should not be used in isolation to confirm or exclude disease. We recommend that future work evaluates the diagnostic accuracy of tests in the context of the diagnostic pathway experienced by the patient and that investigators report how undergoing the MMSE changes patient-relevant outcomes. | Two of the studies had serious design weaknesses with regard to their methods for selecting participants, three with regard to the application of the test (MMSE), and nine with regard to the presentation of flow and timing. We were able to do a combined statistical analysis (meta-analysis) on 28 studies in the community setting (44 articles) and 6 studies in primary care (8 articles), but we could not extract usable data for the remaining 14 community studies. Two of the six studies in primary care were conducted in people who had symptoms of possible dementia. We were able to calculate the summary diagnostic accuracy of the MMSE at three cut points in community-based studies, but we didn't have enough data to do this in the primary care studies. A perfect test would have sensitivity (ability to identify anyone with dementia) of 1.0 (100%) and specificity (ability to identify people without dementia) of 1.0 (100%). For the MMSE, the summary accuracy at a cut point of 25 (10 studies) was sensitivity 0.87 and specificity 0.82. In seven studies that adjusted accuracy estimates for level of education, we found that the test had a sensitivity of 0.97 and specificity of 0.70. The summary accuracy at a cut point of 24 (15 studies) was sensitivity 0.85 and specificity 0.90. Based on these results, we would expect 85% of people with dementia to be correctly identified with the MMSE, while 15% would be wrongly classified as not having dementia; 90% of those tested would be correctly identified as not having dementia whilst 10% would be false positives and might be referred for further testing. Our results support the use of the MMSE as part of the process for deciding whether or not someone has dementia, but the results of the test should be interpreted in broader context of the individual patient, such as their personality, behaviour and how they are managing at home and in daily life. |
Thirteen studies met the inclusion criteria with 8586 participants. Most of the studies were conducted in sub-Saharan Africa. The majority of the studies were of a low or unclear risk of bias. Five studies compared different surgical interventions. Most surgical interventions were performed by non-physician technicians. These trials suggest the most effective surgery is full-thickness incision of the tarsal plate and rotation of the terminal tarsal strip. Pooled data from two studies suggested that the bilamellar rotation was more effective than unilamellar rotation (OR 0.29, 95% CI 0.16 to 0.50). Use of a lid clamp reduced lid contour abnormalities (OR 0.65, 95% CI 0.44 to 0.98) and granuloma formation (OR 0.67, 95% CI 0.46 to 0.97). Absorbable sutures gave comparable outcomes to silk sutures (OR 0.90, 95% CI 0.68 to 1.20) and were associated with less frequent granuloma formation (OR 0.63, 95% CI 0.40 to 0.99). Epilation was less effective at preventing eyelashes from touching the globe than surgery for mild trichiasis, but had comparable results for vision and corneal change. Peri-operative azithromycin reduced post-operative trichiasis; however, the estimate of effect was imprecise and compatible with no effect or increased trichiasis (OR 0.85, 95% CI 0.63 to 1.14; 1954 eyes; 3 studies). Community-based surgery when compared to health centres increased uptake with comparable outcomes. Surgery performed by ophthalmologists and integrated eye care workers was comparable. Adverse events were typically infrequent or mild and included rare postoperative infections, eyelid contour abnormalities and conjunctival granulomas. No trials were designed to evaluate whether the interventions for trichiasis prevent blindness as an outcome; however, several found modest improvement in vision following intervention. Certain interventions have been shown to be more effective at eliminating trichiasis. Full-thickness incision of the tarsal plate and rotation of the lash-bearing lid margin was found to be the best technique and is preferably delivered in the community. Surgery may be carried out by an ophthalmologist or a trained ophthalmic assistant. Surgery performed with silk or absorbable sutures gave comparable results. Post-operative azithromycin was found to improve outcomes where overall recurrence was low. | We identified 13 randomised controlled trials. They were all conducted in trachoma-endemic countries (mostly in sub-Saharan Africa) with surgical interventions carried out by non-physician surgeons. Five studies compared different surgical treatments. Three studies investigated whether azithromycin antibiotic treatment after surgery improves the results. One study compared different types of sutures. One study compared surgery to the pulling out of eyelashes (epilation). One study compared the outcomes of treatments provided in the community with hospital care. One study compared the results of surgery performed by eye doctors with those of non-specialist technicians. The evidence is current to May 2015. Most studies were funded by government research councils or charitable foundations. These trials suggested that the most effective surgery requires full-thickness incision of the tarsal plate and rotation of the edge of the eyelid. The use of a surgical lid clamp improves eyelid contour outcomes and reduces granuloma formation. Silk and absorbable sutures give comparable results. The addition of azithromycin treatment at the time of surgery may reduce post-operative trichiasis under certain conditions. Epilation is less effective than surgery at treating trichiasis, but has comparable results for vision and corneal change two years after intervention. Community-based surgery was more convenient for patients by reducing the time and expense of travelling to a conventional hospital, and it did not increase the risk of complications or recurrence. Surgery performed by ophthalmologists and by integrated eye care workers were both similarly effective. Destroying the lash roots by freezing or electrical ablation appeared to have low success rates and the equipment required is costly and can be difficult to maintain. The quality of the evidence from these randomised controlled trials was variable. Most were of a high quality. However, several were relatively small in size and several had potential bias problems due to the method of randomisation and masking. |
We included five RCTs evaluating the effects of social skills groups in 196 participants with ASD aged 6 to 21 years old. The results show there is some evidence that social skills groups improve overall social competence (ES = 0.47, 95% confidence interval (CI) 0.16 to 0.78, P = 0.003) and friendship quality (ES = 0.41, 95% CI 0.02 to 0.81, P = 0.04) for this population. No differences were found between treatment and control groups in relation to emotional recognition (ES = 0.34, 95% CI -0.20 to 0.88, P = 0.21) assessed in two studies or social communication as related to the understanding of idioms (ES = 0.05, 95% CI -0.63 to 0.72, P = 0.89), which was assessed in only one study. Two additional quality of life outcomes were evaluated, with results of single studies suggesting decreases in loneliness (ES = -0.66, 95% CI -1.15 to -0.17) but no effect on child or parental depression. No adverse events were reported. Given the nature of the intervention and the selected outcome measures, the risk of performance and detection bias are high. There is limited generalizability from the studies as they were all conducted in the US; they focused mainly on children aged 7 to 12, and the participants were all of average or above average intelligence. There is some evidence that social skills groups can improve social competence for some children and adolescents with ASD. More research is needed to draw more robust conclusions, especially with respect to improvements in quality of life. | This review synthesized the results of five randomized controlled trials of social skills groups including 196 individuals with autism spectrum disorders (aged 6 to 21 years). We found individuals receiving treatment showed some indications of improved social competence and better friendships when compared with those not receiving treatment. Participants receiving treatment also showed indications of less loneliness. The ability to recognize different emotions was measured in two studies and there was no evidence that it was improved by taking part in a social skills group. Social communication as it relates to idiomatic expressions was only reported in one study and no significant differences between treatment and control group were found. Nor was there evidence of a beneficial effect of social skills groups on parental or child depression. No adverse effects were reported in the studies. Limitations of this review include a small number of studies and participants, and a high risk of bias due to parents knowing whether their child was in the intervention group or not. The studies focused mainly on children with ASD aged 7 to 12 with average or above average intelligence, and they were all carried out in the US. |
We included 16 studies involving data from 1884 participants. Nine studies included participants considering real clinical trials, and eight included participants considering hypothetical clinical trials, with one including both. All studies were conducted in high-income countries. There is still much uncertainty about the effect of audio-visual informed consent interventions on a range of patient outcomes. However, when considered across comparisons, we found low to very low quality evidence that such interventions may slightly improve knowledge or understanding of the parent trial, but may make little or no difference to rate of participation or willingness to participate. Audio-visual presentation of informed consent may improve participant satisfaction with the consent information provided. However its effect on satisfaction with other aspects of the process is not clear. There is insufficient evidence to draw conclusions about anxiety arising from audio-visual informed consent. We found conflicting, very low quality evidence about whether audio-visual interventions took more or less time to administer. No study measured researcher satisfaction with the informed consent process, nor ease of use. The evidence from real clinical trials was rated as low quality for most outcomes, and for hypothetical studies, very low. We note, however, that this was in large part due to poor study reporting, the hypothetical nature of some studies and low participant numbers, rather than inconsistent results between studies or confirmed poor trial quality. We do not believe that any studies were funded by organisations with a vested interest in the results. The value of audio-visual interventions as a tool for helping to enhance the informed consent process for people considering participating in clinical trials remains largely unclear, although trends are emerging with regard to improvements in knowledge and satisfaction. Many relevant outcomes have not been evaluated in randomised trials. Triallists should continue to explore innovative methods of providing information to potential trial participants during the informed consent process, mindful of the range of outcomes that the intervention should be designed to achieve, and balancing the resource implications of intervention development and delivery against the purported benefits of any intervention. More trials, adhering to CONSORT standards, and conducted in settings and populations underserved in this review, i.e. low- and middle-income countries and people with low literacy, would strengthen the results of this review and broaden its applicability. Assessing process measures, such as time taken to administer the intervention and researcher satisfaction, would inform the implementation of audio-visual consent materials. | We searched for studies of audio-visual informed consent interventions which allocated people to an experimental or control group by a random or quasi-random process, published up until June 2012. We found 16 studies, involving a total of 1884 people. Nine studies included people considering real clinical trials, eight included people asked to imagine participating in a clinical trial (a hypothetical trial), with one including both. Most of the studies were conducted in the United States. People were considering (or imagined considering) participation in a range of different clinical trials, including those testing cancer treatments and drugs for mental health problems. The audio-visual informed consent information was presented on computers, DVDs, videos and CD-ROMs. They included voice overs by professional actors, real patients talking about their experiences and a combination of words, pictures and audio to explain the technical concepts. In some studies, people also received the usual written informed consent forms and/or a face-to-face explanation by the study staff. There is low to very low quality evidence that audio-visual consent interventions may slightly improve knowledge or understanding of the parent trial, but may make little or no difference to rate of participation or willingness to participate. Audio-visual presentation may improve participation satisfaction with the information provided. However its effect on satisfaction with other aspects of the process is not clear. There is not enough evidence to draw conclusions about anxiety arising from audio-visual informed consent. There is conflicting, very low quality evidence about whether audio-visual interventions take more or less time to administer, and no study measured researcher satisfaction with the informed consent process, nor ease of use. We do not believe that any studies were funded by organisations with a vested interest in the results. The quality of evidence from real clinical trials was low, and from hypothetical clinical studies, very low. This is because of the small number of people in the studies, and some issues in the way they were conducted. If the next update of this review includes more studies of audio-visual informed consent presentation, it could change the results of this review. |
We included 16 randomised controlled trials involving a total of 2125 participants. The trials evaluated PAP therapy consisting of ASV or continuous PAP therapy for 1 to 31 months. Many trials included participants with heart failure with reduced ejection fraction. Only one trial included participants with heart failure with preserved ejection fraction. We are uncertain about the effects of PAP therapy on all-cause mortality (RR 0.81, 95% CI 0.54 to 1.21; participants = 1804; studies = 6; I2 = 47%; very low-quality evidence). We found moderate-quality evidence of no difference between PAP therapy and usual care on cardiac-related mortality (RR 0.97, 95% CI 0.77 to 1.24; participants = 1775; studies = 5; I2 = 11%). We found low-quality evidence of no difference between PAP therapy and usual care on all-cause rehospitalisation (RR 0.95, 95% CI 0.70 to 1.30; participants = 1533; studies = 5; I2 = 40%) and cardiac-related rehospitalisation (RR 0.97, 95% CI 0.70 to 1.35; participants = 1533; studies = 5; I2 = 40%). In contrast, PAP therapy showed some indication of an improvement in quality of life scores assessed by all measurements (SMD −0.32, 95% CI −0.67 to 0.04; participants = 1617; studies = 6; I2 = 76%; low-quality evidence) and by the Minnesota Living with Heart Failure Questionnaire (MD −0.51, 95% CI −0.78 to −0.24; participants = 1458; studies = 4; I2 = 0%; low-quality evidence) compared with usual care. Death due to pneumonia (N = 1, 3% of PAP group); cardiac arrest (N = 18, 3% of PAP group); heart transplantation (N = 8, 1% of PAP group); cardiac worsening (N = 3, 9% of PAP group); deep vein thrombosis/pulmonary embolism (N = 1, 3% of PAP group); and foot ulcer (N = 1, 3% of PAP group) occurred in the PAP therapy group, whereas cardiac arrest (N = 16, 2% of usual care group); heart transplantation (N = 12, 2% of usual care group); cardiac worsening (N = 5, 14% of usual care group); and duodenal ulcer (N = 1, 3% of usual care group) occurred in the usual care group across three trials. The effect of PAP therapy on all-cause mortality was uncertain. In addition, although we found evidence that PAP therapy did not reduce the risk of cardiac-related mortality and rehospitalisation, there was some indication of an improvement in quality of life for heart failure patients with CSA. Furthermore, the evidence was insufficient to determine whether adverse events were more common with PAP than with usual care. These findings were limited by low- or very low-quality evidence. PAP therapy may be worth considering for individuals with heart failure to improve quality of life. | We assessed the the quality of evidence for many outcomes including cardiac-related rehospitalisation as low or very low because variability among studies (heterogeneity) was high, a range of confidence intervals was wide, and random sequence generation and blinding of participants and personnel were poorly described. The effect of PAP therapy on all-cause mortality was uncertain. In addition, although PAP therapy did not reduce the risk of cardiac-related mortality and rehospitalisation, there was some indication of an improvement in quality of life score for heart failure patients with CSA. Furthermore, the evidence was insufficient to determine whether adverse events were more common with PAP than with usual care. These findings were limited by low- or very low-quality evidence. PAP therapy may be worth considering for individuals with heart failure to improve quality of life. |
We included 35 studies (1474 participants) in this review. We assessed seven studies at low risk of bias overall, 11 at unclear and the remaining 17 studies at high risk of bias. We present results for our main outcomes, pain and clinical resolution measured at the end of the treatment course (between one week and six months), and adverse effects. The limited evidence available for comparisons between different corticosteroids, and corticosteroids versus alternative or adjunctive treatments is presented in the full review. Corticosteroids versus placebo Three studies evaluated the effectiveness and safety of topical corticosteroids in an adhesive base compared to placebo. We were able to combine two studies in meta-analyses, one evaluating clobetasol propionate and the other flucinonide. We found low-certainty evidence that pain may be more likely to be resolved when using a topical corticosteroid rather than a placebo (RR 1.91, 95% CI 1.08 to 3.36; 2 studies, 72 participants; I² = 0%). The results for clinical effect of treatment and adverse effects were inconclusive (clinical resolution: RR 6.00, 95% CI 0.76 to 47.58; 2 studies, 72 participants; I² = 0%; very low-certainty evidence; adverse effects RR 1.48, 95% 0.48 to 4.56; 3 studies, 88 participants, I² = 0%, very low-certainty evidence). Corticosteroids versus calcineurin inhibitors Three studies compared topical clobetasol propionate versus topical tacrolimus. We found very low-certainty evidence regarding any difference between tacrolimus and clobetasol for the outcomes pain resolution (RR 0.45, 95% CI 0.24 to 0.88; 2 studies, 100 participants; I² = 80%), clinical resolution (RR 0.61, 95% CI 0.38 to 0.99; 2 studies, 52 participants; I² = 95%) and adverse effects (RR 0.05, 95% CI 0.00 to 0.83; 2 studies, 100 participants; very low-certainty evidence) . One study (39 participants) compared topical clobetasol and ciclosporin, and provided only very low-certainty evidence regarding the rate of clinical resolution with clobetasol (RR 3.16, 95% CI 1.00 to 9.93), pain resolution (RR 2.11, 95% CI 0.76 to 5.86) and adverse effects (RR 6.32, 95% CI 0.84 to 47.69). Two studies (60 participants) that compared triamcinolone and tacrolimus found uncertain evidence regarding the rate of clinical resolution (RR 0.86, 95% CI 0.55 to 1.35; very low-certainty evidence) and that there may be a lower rate of adverse effects in the triamcinolone group (RR 0.47, 95% CI 0.22 to 0.99; low-certainty evidence). These studies did not report on pain resolution. Corticosteroids have been first line for the treatment of OLP. This review found that these drugs, delivered topically as adhesive gels or similar preparations, may be more effective than placebo for reducing the pain of symptomatic OLP; however, with the small number of studies and participants, our confidence in the reliability of this finding is low. The results for clinical response were inconclusive, and we are uncertain about adverse effects. Very low-certainty evidence suggests that calcineurin inhibitors, specifically tacrolimus, may be more effective at resolving pain than corticosteroids, although there is some uncertainty about adverse effects and clinical response to tacrolimus showed conflicting results. | The evidence in this review is up-to-date as of 25 February 2019. We included 35 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 1474 participants, which tested several different corticosteroids, mostly delivered topically (on the skin). Corticosteroids were compared with one of the following: a placebo (a treatment that resembled the corticosteroid but had no active ingredient); a medicine from a category called calcineurin inhibitors; another medicine type; another corticosteroid or mode of delivery; the same corticosteroid plus an extra treatment; or an alternative treatment. Treatments were given for between one week and six months, with side effects measured throughout the treatment, and pain and healing measured at the end of treatment. Results from two studies showed that topical corticosteroids (e.g. clobetasol propionate, flucinonide, betamethasone and triamcinolone acetonide), when applied to the mouth in a sticky cream, may be effective in reducing and stopping pain. We do not have the evidence that topical corticosteroids can eliminate the oral lichen planus lesions, and we are uncertain about side effects. We found no consistent evidence that any particular corticosteroid was better than any other. Three studies using another topical medicine called tacrolimus (a calcineurin inhibitor) found that this medicine may be more effective than corticosteroids, but may be more likely to cause mild side effects. Available evidence comparing corticosteroids with other treatments is very limited. The reliability of most of the evidence is very low, so we cannot be sure about the findings and future research may lead us to different conclusions. The available evidence suggests that topical corticosteroids may be effective for treating painful oral lichen planus, but our confidence in these findings is limited as there were only a small number of studies and participants. There is some evidence that tacrolimus may be more effective than a corticosteroid, but evidence on negative side effects is inconclusive. |
We included two randomised trials with a total of 581 women each comparing different regimens of titrated oral misoprostol with intravenous oxytocin. One study compared 20 mcg doses of misoprostol dissolved in water (repeated every hour up to four hours, after which the dose was increased to 40 mcg per hour up to a maximum total dose of 1600 mcg), while the second study gave women 75 mcg doses (repeated after four hours provided there were no adverse effects observed). Neither trial reported maternal death, severe maternal morbidity, or fetal/neonatal mortality outcomes, and only a few fetal/neonatal morbidity outcomes were considered, none of which were significantly different between groups. For several outcomes (such as maternal side-effects, instrumental birth, maternal blood transfusion for hypovolaemia and epidural analgesia), the number of events was generally too low for sufficient statistical power to be achieved. Maternal satisfaction was not reported in either trial. One trial reported a slight reduction in the median duration of labour from the start of augmentation to vaginal delivery in the oxytocin group. Neither trial reported significantly higher rates of caesarean section (CS) in the oral misoprostol group. Rates of vaginal delivery within 12 and 24 hours of commencing augmentation were not significantly different in the trial using a 20 mcg misoprostol dose. Neither trial had significantly higher rates of uterine hyperstimulation with fetal heart rate changes in the titrated oral misoprostol group. However, the rates of this outcome varied so greatly between the two studies as to suggest that other factors were at play. The only significant differences between groups related to uterine hyperstimulation (without fetal heart rate changes), and results were not consistent in the two trials. In the trial examining the higher dose of misoprostol, more women in the misoprostol group experienced hyperstimulation of labour measured over a 10-minute period compared with those receiving oxytocin (risk ratio (RR) 1.17, 95% confidence interval (CI) 1.02 to 1.35, 350 women). In the study examining the lower titrated dose of misoprostol, there was a lower incidence of tachysystole when labour was augmented with titrated oral misoprostol than with oxytocin (RR 0.39, 95% CI 0.17 to 0.91, 231 women) with no occurrences of hypertonus in either group of women. Important uncertainties still exist on the safety and acceptability of titrated oral misoprostol compared with intravenous oxytocin regimens in women with dystocia following spontaneous onset of labour. Although in facilities where electronic oxytocin infusion is not available, low-dose titrated misoprostol may offer a better alternative to an uncontrolled oxytocin infusion to avoid hyperstimulation. Further research is needed in both high- and low-resource settings More trials should be conducted to evaluate the effect of a standard titration oral misoprostol regimen, both following spontaneous labour and labour induction. Comparisons with other augmentation methods are also warranted, as are any effects on women's birth experiences. | We identified two randomised controlled trials with 581 women requiring augmentation, each looking at different doses of oral misoprostol compared with oxytocin. One study gave 20 mcg doses of misoprostol every hour up to four hours, after which the dose was increased; the second gave women 75 mcg doses, repeated after four hours provided there were no adverse effects observed. Neither trial reported on the important safety outcomes of maternal or neonatal deaths, or severe maternal ill health. One trial measured duration of labour from the start of augmentation, which was slightly shorter with intravenous oxytocin (5.20 hours compared with 5.22 hours). The number of vaginal deliveries within 12 and 24 hours, and caesarean section rates were similar. Neither trial reported clearly higher rates of uterine hyperstimulation with worrying fetal heart rate changes in the titrated oral misoprostol group. The rates of this outcome in the two studies varied greatly however. The evidence on uterine hyperstimulation without fetal heart rate changes was not consistent. The number of women reporting nausea, vomiting, shivering and pyrexia was low with both misoprostol and oxytocin. Maternal satisfaction was not reported in either trial. Important uncertainties still exist on the safety and acceptability of titrated oral misoprostol for labour dystocia, and further research is needed before it can be recommended as an alternative to oxytocin. However, in facilities that do not have access to electronic oxytocin infusion, lower doses of titrated misoprostol may be a better alternative to avoid hyperstimulation. |
We identified 4245 possible studies from the initial search. Of those studies, four studies (256 participants) met the inclusion criteria. One more study is awaiting classification. Studies were, conducted in single-centre surgical and mixed medical-surgical ICUs. BIS monitor was used to assess the level of sedation in the intervention arm in all the studies. In the control arm, the sedation assessment tools for CA included the Sedation-Agitation Scale (SAS), Ramsay Sedation Scale (RSS) or subjective CA utilizing traditional clinical signs (heart rate, blood pressure, conscious level and pupillary size). Only one study was classified as low risk of bias, the other three studies were classified as high risk. There was no evidence of a difference in one study (N = 50) that measured ICU LOS (Median (Interquartile Range IQR) 8 (4 to 14) in the CA group; 12 (6 to 18) in the BIS group; low-quality evidence).There was little or no effect on the duration of mechanical ventilation (MD -0.02 days (95% CI -0.13 to 0.09; 2 studies; N = 155; I2 = 0%; low-quality evidence)). Adverse events were reported in one study (N = 105) and the effects on restlessness after suction, endotracheal tube resistance, pain tolerance during sedation or delirium after extubation were uncertain due to very low-quality evidence. Clinically relevant adverse events such as self-extubation were not reported in any study. Three studies reported the amount of sedative agents used. We could not measure combined difference in the amount of sedative agents used because of different sedation protocols and sedative agents used in the studies. GRADE quality of evidence was very low. No study reported other secondary outcomes of interest for the review. We found insufficient evidence about the effects of BIS monitoring for sedation in critically ill mechanically ventilated adults on clinical outcomes or resource utilization. The findings are uncertain due to the low- and very low-quality evidence derived from a limited number of studies. | The evidence identified from our literature search is current to May 2017. Four randomized controlled studies met the inclusion criteria for this review (involving 256 adults). One more study is awaiting classification. These studies were conducted in adult surgical and mixed medical-surgical ICUs, and compared BIS monitoring with various measures for CA. For one study, the BIS monitoring devices manufacturer provided equipment. The company had no role in the conduct of the study. Another study was funded as part of a scientific and technological project. No funding information was available for the other two studies. With BIS monitoring, we found no significant differences in ICU length of stay (one study, 50 adults), duration of ventilation (two studies, 155 adults) and the risk of adverse events (one study, 105 adults) compared with CA. Clinically relevant adverse events, for example, accidental self-removal of the breathing tube, were not reported. We could not measure combined difference in amount of sedative use because of the different sedation protocols and sedatives used. None of the other outcomes of interest for the review, for example, death, ventilator-associated pneumonia, quality of life etc. were reported in any of the studies. The findings of our review are from a limited number of studies which provided 'low to very low' GRADE quality of evidence. The authors of this review conclude that we found insufficient evidence about the effects of BIS monitoring compared with CA of sedation in critically ill adults who were on a ventilator. |
We included 17 observational studies in this review. We found no randomized controlled trials. Twelve studies are based in hospitals, three in prisons and two in universities. Three studies used a controlled before-and-after design, with another site used for comparison. The remaining 14 studies used an uncontrolled before-and-after study design. Five studies reported evidence from two participant groups, including staff and either patients or prisoners (depending on specialist setting), with the 12 remaining studies investigating only one participant group. The four studies (two in prisons, two in hospitals) providing health outcomes data reported an effect of reduced secondhand smoke exposure and reduced mortality associated with smoking-related illnesses. No studies included in the review measured cotinine levels to validate secondhand smoke exposure. Eleven studies reporting active smoking rates with 12,485 participants available for pooling, but with substantial evidence of statistical heterogeneity (I² = 72%). Heterogeneity was lower in subgroups defined by setting, and provided evidence for an effect of tobacco bans on reducing active smoking rates. An analysis exploring heterogeneity within hospital settings showed evidence of an effect on reducing active smoking rates in both staff (risk ratio (RR) 0.71, 95% confidence interval ( CI) 0.64 to 0.78) and patients (RR 0.86, 95% CI 0.76 to 0.98), but heterogeneity remained in the staff subgroup (I² = 76%). In prisons, despite evidence of reduced mortality associated with smoking-related illnesses in two studies, there was no evidence of effect on active smoking rates (1 study, RR 0.99, 95% CI 0.84 to 1.16). We judged the quality of the evidence to be low, using the GRADE approach, as the included studies are all observational. We found evidence of an effect of settings-based smoking policies on reducing smoking rates in hospitals and universities. In prisons, reduced mortality rates and reduced exposure to secondhand smoke were reported. However, we rated the evidence base as low quality. We therefore need more robust studies assessing the evidence for smoking bans and policies in these important specialist settings. | Studies have shown that workplaces providing services to help smokers to stop smoking have been effective. Services can include providing nicotine replacement therapy (NRT) and counselling support to help smokers quit. However, it is not known if policies that stop people smoking in institutions are effective. Whilst smoking is banned in many public places, it is not banned in all of them. Smoking is allowed in some healthcare organisations, universities and prisons. Study characteristics We searched for studies that measured whether introducing a smoking policy or ban, in hospitals, universities or prisons, reduced secondhand smoke exposure and helped people to quit smoking. The study could be in any language. It had to report information on health and smoking before the policy or ban started and for at least six months afterwards. We have included 17 studies in this review. Twelve studies provide evidence from hospitals, three from prisons and two from universities. The evidence is up-to-date to June 2015. Key results We grouped together 11 of the included studies, involving 12,485 people, and found that banning smoking in hospitals and universities increased the number of smoking quit attempts and reduced the number of people smoking. In prisons, there was a reduction in the number of people who died from diseases related to smoking and a reduction in exposure to secondhand smoke after policies and bans were introduced, but there was no evidence of reduced smoking rates. Quality of the evidence We found no relevant high-quality studies to include in our review. Future high-quality research may lead to a change in these conclusions and it is not possible to draw firm conclusions from the current evidence. We need more research from larger studies to investigate smoking bans and policies in these important settings. |
Nineteen studies were identified that met the inclusion criteria. Most patients in the studies had neurogenic OAB, but some included patients with idiopathic OAB. All studies demonstrated superiority of botulinum toxin to placebo. Lower doses of botulinum toxin (100 to 150 U) appeared to have beneficial effects, but larger doses (300 U) may have been more effective and longer lasting, but with more side effects. Suburothelial injection had comparable efficacy to intradetrusor injection. The effect of botulinum toxin may last for a number of months and is dependent upon dose and type of toxin used. Patients receiving repeated doses do not seem to become refractory to botulinum toxin. Botulinum toxin appeared to have beneficial effects in OAB that quantitatively exceeded the effects of intravesical resiniferatoxin. Intravesical botulinum toxin appeared to be reasonably safe; however, one study was halted due to a perceived unacceptable rate of urinary retention. Intravesical botulinum toxin appears to be an effective therapy for refractory OAB symptoms, but as yet little controlled trial data exist on benefits and safety compared with other interventions, or with placebo. Further robust data are required on long term outcomes, safety, and optimal dose of botulinum toxin for OAB. | We found that there were several comparative studies, but these involved a relatively small number of patients. There was evidence that botulinum toxin improves the symptoms of OAB. It was unclear what the best dose of botulinum toxin was. Botulinum toxin injections into the bladder appeared to give few side effects or complications, but there were no long-term follow-up studies, and there could be rare side effects that have not been discovered yet. |
We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration ranged from 10 days to 180 days. Eight trials declared their funding source, of which six were independently funded and two were industry funded. The remaining 13 trials did not disclose their funding source. We classified 19 of the 21 trials at high risk of bias. We found no effect on all-cause mortality when probiotics were compared with placebo or no treatment (7 trials; 404 participants; RR 0.58, 95% CI 0.23 to 1.44; low-quality evidence). No-recovery (as measured by incomplete resolution of symptoms) was lower for participants treated with probiotic (10 trials; 574 participants; RR 0.67, 95% CI 0.56 to 0.79; moderate-quality evidence). Adverse events were lower for participants treated with probiotic than with no intervention when considering the development of overt hepatic encephalopathy (10 trials; 585 participants; RR 0.29, 95% CI 0.16 to 0.51; low-quality evidence), but effects on hospitalisation and change of/or withdrawal from treatment were uncertain (hospitalisation: 3 trials, 163 participants; RR 0.67, 95% CI 0.11 to 4.00; very low-quality evidence; change of/or withdrawal from treatment: 9 trials, 551 participants; RR 0.70, 95% CI 0.46 to 1.07; very low-quality evidence). Probiotics may slightly improve quality of life compared with no intervention (3 trials; 115 participants; results not meta-analysed; low-quality evidence). Plasma ammonia concentration was lower for participants treated with probiotic (10 trials; 705 participants; MD -8.29 μmol/L, 95% CI -13.17 to -3.41; low-quality evidence). There were no reports of septicaemia attributable to probiotic in any trial. When probiotics were compared with lactulose, the effects on all-cause mortality were uncertain (2 trials; 200 participants; RR 5.00, 95% CI 0.25 to 102.00; very low-quality evidence); lack of recovery (7 trials; 430 participants; RR 1.01, 95% CI 0.85 to 1.21; very low-quality evidence); adverse events considering the development of overt hepatic encephalopathy (6 trials; 420 participants; RR 1.17, 95% CI 0.63 to 2.17; very low-quality evidence); hospitalisation (1 trial; 80 participants; RR 0.33, 95% CI 0.04 to 3.07; very low-quality evidence); intolerance leading to discontinuation (3 trials; 220 participants; RR 0.35, 95% CI 0.08 to 1.43; very low-quality evidence); change of/or withdrawal from treatment (7 trials; 490 participants; RR 1.27, 95% CI 0.88 to 1.82; very low-quality evidence); quality of life (results not meta-analysed; 1 trial; 69 participants); and plasma ammonia concentration overall (6 trials; 325 participants; MD -2.93 μmol/L, 95% CI -9.36 to 3.50; very low-quality evidence). There were no reports of septicaemia attributable to probiotic in any trial. The majority of included trials suffered from a high risk of systematic error (‘bias’) and a high risk of random error (‘play of chance’). Accordingly, we consider the evidence to be of low quality. Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but probiotics may lead to little or no difference in mortality. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence is very low. High-quality randomised clinical trials with standardised outcome collection and data reporting are needed to further clarify the true efficacy of probiotics. | The evidence is current to June 2016. Of the 21 included trials including 1420 participants, 14 trials compared a probiotic with placebo or no treatment and seven trials compared a probiotic with lactulose. The treatment duration of the trials ranged from 10 days to 180 days. Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but may lead to little or no difference in mortality. Probiotics may slightly improve quality of life when compared with no intervention; however, this conclusion is based on three trials with low-quality evidence. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence was very low. There were no reports of septicaemia attributable to probiotic in any trial. There was no evidence of more adverse events with probiotics when compared to placebo or lactulose. Eight trials declared their funding source, of which six were independently funded and two were industry funded. The remaining 13 trials did not disclose their funding source. Many of the included trials suffered from a high risk of systematic error (‘bias’) and a high risk of random error (‘play of chance’). Accordingly, we consider the evidence to be of low quality. Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but probiotics may lead to little or no difference in mortality. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence was very low. High-quality randomised clinical trials with standardised outcome collection and data reporting are needed to further clarify the true efficacy of probiotics. |
In total, the search identified 2102 records, of which we reviewed 144 in full text. We included eight studies. Four interventions focused on patient–caregiver dyads and four were aimed specifically at the caregiver. Heterogeneity of populations and methodologies precluded meta-analysis. Risk of bias varied, and all studies included only small numbers of neuro-oncology caregivers (13 to 56 participants). There was some evidence for positive effects of caregiver support on psychological distress, mastery, and quality of life (low to very low certainty of evidence). No studies reported significant effects on caregiver burden or quality of patient–caregiver relationship (low to very low certainty of evidence). None of the studies assessed caregiver physical functioning. For secondary outcomes (patient emotional or physical well-being; health economic effects), we found very little to no evidence for the effectiveness of caregiver support. We identified five ongoing trials. The eight small-scale studies included employed different methodologies across different populations, with low certainty of evidence overall. It is not currently possible to draw reliable conclusions regarding the effectiveness of supportive interventions aimed at improving neuro-oncology caregiver well-being. More high-quality research is needed on support for family caregivers of people diagnosed, and living, with a brain or spinal cord tumour. | We included eight clinical studies. Four studies reported on interventions for patient–caregiver relationship and four studies were aimed specifically at improving caregiver well-being. We found five ongoing studies. The interventions tested were diverse in nature (e.g. cognitive behavioural therapy (talking therapy); psychoeducation (providing education and information to people seeking or receiving mental health services); coping skills training; self-management; social network intervention); and delivery (e.g. face-to-face; web-based), and all studies were relatively small (included between 13 and 56 neuro-oncology caregivers). We found some evidence for positive effects of caregiver support on psychological distress, feelings of mastery (i.e. the feeling of being in control of the caregiving situation), and quality of life. None of the studies reported effects on caregiver burden or quality of patient–caregiver relationship. None of the studies measured caregiver physical well-being. Overall, the certainty of the evidence was low to very low, which means the true effect of caregiver support may be substantially different. Our findings suggest it is not currently possible to draw definitive conclusions about the effectiveness of supportive interventions to improve neuro-oncology caregiver well-being. More high-quality research is needed on support for family caregivers of patients diagnosed, and living, with a brain or spinal cord tumour. |
Only seven studies were included. Major methodological limitations such as small trial size and large confidence intervals decreased the power of the studies to detect differences between treatments, and meta-analysis of data was not possible for the majority of outcomes. Four placebo-controlled trials did not find evidence that antidepressants improved weight gain, eating disorder or associated psychopathology. Isolated findings, favouring amineptine and nortriptyline, emerged from the antidepressant versus antidepressant comparisons, but cannot be conceived as evidence of efficacy of a specific drug or class of antidepressant in light of the findings from the placebo comparisons. Non-completion rates were similar between the compared groups. A lack of quality information precludes us from drawing definite conclusions or recommendations on the use of antidepressants in acute AN. Future studies testing safer and more tolerable antidepressants in larger, well designed trials are needed to provide guidance for clinical practice. | The aim of the present review was to evaluate the evidence from randomised controlled trials for the efficacy and acceptability of antidepressant treatment in acute AN. Seven small studies were identified; four placebo-controlled trials did not find evidence of efficacy of antidepressants in improving weight gain, eating disorder or associated symptoms, as well as differences in completion rates. Meta-analysis of data was not possible for most outcomes. However, major methodological limitations of these studies (e.g. insufficient power to detect differences) prevent from drawing definite conclusions or recommendations for antidepressant use in acute AN. Further studies testing safer antidepressants in larger and well designed trials are needed to guide clinical practice. |
From 71 papers describing IQCODE test accuracy, we included 1 paper, representing data from 230 individuals (n=16 [7%] with dementia). The paper described those patients consulting a primary care service who self-identified as Japanese-American. Dementia diagnosis was made using Benson & Cummings criteria and the IQCODE was recorded as part of a longer interview with the informant. IQCODE accuracy was assessed at various test thresholds, with a "trade-off" between sensitivity and specificity across these cutpoints. At an IQCODE threshold of 3.2 sensitivity: 100%, specificity: 76%; for IQCODE 3.7 sensitivity: 75%, specificity: 98%. Applying the QUADAS-2 assessments, the study was at high risk of bias in all categories. In particular degree of blinding was unclear and not all participants were included in the final analysis. It is not possible to give definitive guidance on the test accuracy of IQCODE for the diagnosis of dementia in a primary care setting based on the single study identified. We are surprised by the lack of research using the IQCODE in primary care as this is, arguably, the most appropriate setting for targeted case finding of those with undiagnosed dementia in order to maximise opportunities to intervene and provide support for the individual and their carers. | We searched differing databases of published research for all papers relating to the accuracy of IQCODE for detecting dementia. We found only one study that tested diagnostic accuracy of IQCODE in a primary care/general practice setting. The study was of a select population (Japanese Americans) and the results may not be applicable to patients in other countries. We also noted issues in the study methods used and the reported results. Based on this single study we are unable to give guidance on how well IQCODE may function as a dementia assessment in primary care. More research is needed in this area as many patients with memory or thinking problems will first consult their general practitioner / family doctor. |
We included one randomised controlled trial involving 64 participants with schizophrenia or schizoaffective disorder. The average age of participants was 54 years; participants had been living with type 2 diabetes for on average nine years, and with their psychiatric diagnosis since they were on average 28 years of age. Investigators evaluated the 24-week Diabetes Awareness and Rehabilitation Training (DART) programme in comparison with usual care plus information (UCI). Follow-up after trial completion was six months. Risk of bias was mostly unclear but was high for selective reporting. Trial authors did not report on diabetes-related complications, all-cause mortality, adverse events, health-related quality of life nor socioeconomic effects. Twelve months of data on self care behaviours as measured by total energy expenditure showed a mean of 2148 kcal for DART and 1496 kcal for UCI (52 participants; very low-quality evidence), indicating no substantial improvement. The intervention did not have a substantial effect on glycosylated haemoglobin A1c (HbA1c) at 6 or 12 months of follow-up (12-month HbA1c data 7.9% for DART vs 6.9% for UCI; 52 participants; very low-quality evidence). Researchers noted small improvements in body mass index immediately after the intervention was provided and at six months, along with improved weight post intervention. Diabetes knowledge and self efficacy improved immediately following receipt of the intervention, and knowledge also at six months. The intervention did not improve blood pressure. Evidence is insufficient to show whether type 2 diabetes self management interventions for people with severe mental illness are effective in improving outcomes. Researchers must conduct additional trials to establish efficacy, and to identify the active ingredients in these interventions and the people most likely to benefit from them. | We identified one study, which recruited 64 adults with type 2 diabetes and schizophrenia or schizoaffective disorder. Researchers compared usual care plus information leaflets with a 24-week education programme delivered once a week for 90 minutes (Diabetes Awareness and Rehabilitation Training). This programme provided basic diabetes education and information about nutrition and exercise. The average age of participants was 54 years; participants had been living with type 2 diabetes for on average nine years and with their psychiatric diagnosis since they were on average 28 years old. People in the included study were monitored for six months after the programme ended. This evidence is up to date as of 07 March 2016. In summary, few studies have evaluated the effects of diabetes self management programmes for adults with severe mental illness. Study authors of the single included study did not report diabetes-related complications, all-cause mortality, adverse events, health-related quality of life nor socioeconomic effects. They described small improvements in body mass index and body weight, as well as in diabetes knowledge and self efficacy. Current evidence is insufficient to show that these types of programmes can help people with type 2 diabetes and severe mental illness to better manage their diabetes and its consequences. We rated the overall quality of the evidence as very low, mainly because of the small numbers of included studies and participants, and because reported study results showed inconsistency. |
One randomised trial involving 14 preterm infants was included. There was no evidence of a clear difference between the fat-supplemented and unsupplemented groups in in-hospital rates of growth in weight (MD 0.6 g/kg/day, 95% CI −2.4 to 3.6; 1 RCT, n = 14 infants, very low-quality evidence), length (MD 0.1 cm/week, 95% CI −0.08 to 0.3; 1 RCT, n = 14 infants, very low-quality evidence) and head circumference (MD 0.2 cm/week, 95% CI −0.07 to 0.4; 1 RCT n = 14 infants, very low-quality evidence). There was no clear evidence that fat supplementation increased the risk of feeding intolerance (RR 3.0, 95% CI 0.1 to 64.3; 1 RCT, n = 16 infants, very low-quality evidence). No data were available regarding the effects of fat supplementation on long-term growth, body mass index, body composition, neurodevelopmental, or cardio-metabolic outcomes. The one included trial suggests no evidence of an effect of fat supplementation of human milk on short-term growth and feeding intolerance in preterm infants. However, the very low-quality evidence, small sample size, few events, and low precision diminishes our confidence that these results reflect the true effect of fat supplementation of human milk in preterm infants, and no long-term outcomes were reported. Further high-quality research should evaluate the effect on short and long-term growth, neurodevelopmental and cardio-metabolic outcomes in the context of the development of multicomponent fortifiers. Optimal dosage, adverse effects, and delivery practices should also be evaluated. | We included one trial with very low-quality evidence and involving 14 preterm infants. The search is up to date as of February 2018. Addition of extra fat to human milk for preterm infants showed no clear benefits with regards to short-term rates of weight gain, length gain, and head growth. There was no evidence that the extra fat increased the risk of feeding intolerance. No data were available regarding the effects of addition of extra fat on long-term growth, body fat, obesity, high blood sugar, or brain development. There were also limited data to assess side effects. There was insufficient high-quality evidence on the benefits and harms of the addition of extra fat to human milk in preterm infants, and no long-term outcomes have been reported. Since addition of extra fat to human milk is currently done as part of multi-nutrient fortification, future trials should evaluate the effect of the fat component on short- and long-term growth, body fat, obesity, high blood sugar, or brain development. The right amount and composition of extra fat needed, side effects, and delivery practices should also be evaluated. |
Four studies were included involving 640 primary care physicians and more than 6400 patients. There was considerable variation in study setting and the range of outcomes measured. FFS resulted in more primary care visits/contacts, visits to specialists and diagnostic and curative services but fewer hospital referrals and repeat prescriptions compared with capitation. Compliance with a recommended number of visits was higher under FFS compared with capitation payment. FFS resulted in more patient visits, greater continuity of care, higher compliance with a recommended number of visits, but patients were less satisfied with access to their physician compared with salaried payment. It is noteworthy that so few studies met the inclusion criteria. There is some evidence to suggest that the method of payment of primary care physicians affects their behaviour, but the findings' generalisability is unknown. More evaluations of the effect of payment systems on PCP behaviour are needed, especially in terms of the relative impact of salary versus capitation payments. | This review examined the impact of different payment systems on primary care physician behaviour. Three payment systems were included: capitation (payment is made for every patient for whom care is provided), salary, and fee for service (payment is made for every item of care provided). There was some evidence that primary care physicians provide a greater quantity of primary care services under fee for service payment compared with capitation and salary, although long-term effects are unclear. There was no evidence, however, concerning other important outcomes such as patient health status, or comparing the relative impact of salary versus capitation payment. |
We retrieved 1111 publications of which 51 satisfied our inclusion criteria. In total there were 2871 participants (1645 active, 1226 placebo), each receiving on average 18 injections. Duration of immunotherapy varied from three days to three years. Symptom score data from 15 trials were suitable for meta-analysis and showed an overall reduction in the immunotherapy group (SMD -0.73 (95% CI -0.97 to -0.50, P < 0.00001)). Medication score data from 13 trials showed an overall reduction in the immunotherapy group (SMD of -0.57 (95% CI -0.82 to -0.33, p<0.00001)). Clinical interpretation of the effect size is difficult. Adrenaline was given in 0.13% (19 of 14085 injections) of those on active treatment and in 0.01% (1 of 8278 injections) of the placebo group for treatment of adverse events. There were no fatalities. This review has shown that specific allergen injection immunotherapy in suitably selected patients with seasonal allergic rhinitis results in a significant reduction in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events. | We identified randomised, double-blind, placebo controlled trials of specific allergen immunotherapy in patients with seasonal allergic rhinitis due to tree, grass or weed pollens. Fifty-one studies satisfied our inclusion criteria. In total there were 2871 participants (1645 in the treatment groups and 1226 in the placebo), each receiving on average 18 injections. The duration of treatment varied from three days to three years. This review has shown that injection immunotherapy in suitably selected patients with hay fever results in significant reductions in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events and no fatalities. |
We included 11 randomised controlled studies with 735 participants which produced 16 meta-analyses of outcome data. Meta-analysis indicated that the primary outcome of intervention failure, occurred in lower proportion of participants with PEG compared to NGT (RR 0.18, 95% CI 0.05 to 0.59, eight studies, 408 participants, low quality evidence) and this difference was statistically significant. For this outcome, we also subgrouped the studies by endoscopic gastrostomy technique into pull, and push and not reported. We observed a significant difference favouring PEG in the pull subgroup (RR 0.07, 95% CI 0.01 to 0.35, three studies, 90 participants). Thepush subgroup contained only one clinical trial and the result favoured PEG (RR 0.05, 95% CI 0.00 to 0.74, one study, 33 participants) techniques. We found no statistically significant difference in cases where the technique was not reported (RR 0.43, 95% CI 0.13 to 1.44, four studies, 285 participants). There was no statistically significant difference between the groups for meta-analyses of the secondary outcomes of mortality (RR 0.86, 95% CI 0.58 to 1.28, 644 participants, nine studies, very low quality evidence), overall reports of any adverse event at any follow-up time point (ITT analysis, RR 0.83, 95% CI 0.51 to 1.34), 597 participants, 6 studies, moderate quality evidence), specific adverse events including pneumonia (aspiration) (RR 0.70, 95% CI 0.46 to 1.06, 645 participants, seven studies, low quality evidence), or for the meta- analyses of the secondary outcome of nutritional status including weight change from baseline, and mid-arm circumference at endpoint, although there was evidence in favour of PEG for meta-analyses of mid-arm circumference change from baseline (MD 1.16, 95% CI 1.01 to 1.31, 115 participants, two studies), and levels of serum albumin were higher in the PEG group (MD 6.03, 95% CI 2.31 to 9.74, 107 participants). For meta-analyses of the secondary outcomes of time on enteral nutrition, there was no statistically significant difference (MD 14.48, 95% CI -2.74 to 31.71; 119 participants, two studies). For meta-analyses of quality of life measures (EuroQol) outcomes in two studies with 133 participants, for inconvenience (RR 0.03, 95% CI 0.00 to 0.29), discomfort (RR 0.03, 95% CI 0.00 to 0.29), altered body image (RR 0.01, 95% CI 0.00 to 0.18; P = 0.001) and social activities (RR 0.01, 95% CI 0.00 to 0.18) the intervention favoured PEG, that is, fewer participants found the intervention of PEG to be inconvenient, uncomfortable or interfered with social activities. However, there were no significant differences between the groups for pain, ease of learning to use, or the secondary outcome of length of hospital stay (two studies, 381 participants). PEG was associated with a lower probability of intervention failure, suggesting the endoscopic procedure may be more effective and safe compared with NGT. There is no significant difference in mortality rates between comparison groups, or in adverse events, including pneumonia related to aspiration. Future studies should include details of participant demographics including underlying disease, age and gender, and the gastrostomy technique. | We obtained updated evidence for this review from 11 randomised controlled studies comparing a nasogastric tube with PEG in a total of 735 patients. Seven studies measured treatment failure i.e. feeding interruption, blocking or leakage of the feeding tube in 408 patients randomised to either a nasal gastric tube or PEG. The studies showed a higher probability of treatment failure with a nasal gastric tube. The number of deaths was no different with the two methods; nor was the overall occurrence of adverse events. Participants with PEGs may have a better quality of life. Possible limitations of this review include the small number of participants in the majority of studies, explained by the high cost of PEG and requirements for endoscopy in its use, the operational challenges to accomplish a clinical trial in this area and the different length of follow-up of the patients in the studies (from less than four weeks to six months). There were clinical differences between the trials, with the participants having different baseline diseases and different techniques used to insert the PEG. The findings of the present review of the literature should be interpreted with caution, given that there were methodological issues with most of the included studies which increase the risk of bias in the trial. This systematic review of the literature is valuable in analysing 11 studies, with a sample size of 735 patients. Nevertheless, further randomised clinical trials that adopt a rigorous method are warranted. |
We included 12 studies with a total of 1834 participants in this updated review. The methodological quality of the included studies was difficult to assess as it was poorly reported, so the predominant classification of bias was 'unclear'; the studies did not report on compliance with the prescribed therapy. We were able to include data from only 1160 patients in the meta-analysis. Four trials (152 patients) compared the effects of IS with no respiratory treatment. We found no statistically significant difference between the participants receiving IS and those who had no respiratory treatment for clinical complications (relative risk (RR) 0.59, 95% confidence interval (CI) 0.30 to 1.18). Two trials (194 patients) IS compared incentive spirometry with deep breathing exercises (DBE). We found no statistically significant differences between the participants receiving IS and those receiving DBE in the meta-analysis for respiratory failure (RR 0.67, 95% CI 0.04 to 10.50). Two trials (946 patients) compared IS with other chest physiotherapy. We found no statistically significant differences between the participants receiving IS compared to those receiving physiotherapy in the risk of developing a pulmonary condition or the type of complication. There was no evidence that IS is effective in the prevention of pulmonary complications. There is low quality evidence regarding the lack of effectiveness of incentive spirometry for prevention of postoperative pulmonary complications in patients after upper abdominal surgery. This review underlines the urgent need to conduct well-designed trials in this field. There is a case for large RCTs with high methodological rigour in order to define any benefit from the use of incentive spirometry regarding mortality. | We included adults (aged 18 years and above) admitted for any type of upper abdominal surgery. The evidence is current to August 2013. We found 12 studies with a total of 1834 participants. The maximum period of time that a patient was followed by the doctor was seven days postoperatively. The quality of the included studies was uncertain because of poor reporting in the published articles. The following results were examined in this review: clinical complications, respiratory failure (that is, inadequate gas exchange by the respiratory system), and pulmonary complications. The results from participants receiving IS were the same as for those receiving either no treatment, deep breathing exercises (DBE) or physiotherapy in the meta-analyses for clinical complications, respiratory failure, and pulmonary complications. Because of poorly conducted studies (results not similar across studies; some issues with study design and; not enough data collected and organized) we ranked the overall quality of the evidence reported in this review as low. There is low quality evidence showing a lack of effectiveness of incentive spirometry for prevention of postoperative pulmonary complications in patients after upper abdominal surgery. This review underlines the urgent need to conduct well-designed trials in this field. |
We identified no completed or ongoing RCTs, nRCTs, CBAs, or ITSs. No studies included people undergoing an epidural procedure. No studies compared different platelet count thresholds prior to a procedure. In this update we identified three retrospective cohort studies that contained participants who did and did not receive platelet transfusions prior to lumbar puncture procedures. All three studies were carried out in people with cancer, most of whom had a haematological malignancy. Two studies were in children, and one was in adults. The number of participants receiving platelet transfusions prior to the lumbar puncture procedures was not reported in one study. We therefore only summarised in a narrative form the relevant outcomes from two studies (150 participants; 129 children and 21 adults), in which the number of participants who received the transfusion was given. We judged the overall risk of bias for all reported outcomes for both studies as 'serious' based on the ROBINS-I tool. No procedure-related major bleeding occurred in the two studies that reported this outcome (2 studies, 150 participants, no cases, very low-quality evidence). There was no evidence of a difference in the risk of minor bleeding (traumatic tap) in participants who received platelet transfusions before a lumbar puncture and those who did not receive a platelet transfusion before the procedure (2 studies, 150 participants, very low-quality evidence). One of the 14 adults who received a platelet transfusion experienced minor bleeding (traumatic tap; defined as at least 500 x 106/L red blood cells in the cerebrospinal fluid); none of the seven adults who did not receive a platelet transfusion experienced this event. Ten children experienced minor bleeding (traumatic taps; defined as at least 100 x 106/L red blood cells in the cerebrospinal fluid), six out of the 57 children who received a platelet transfusion and four out of the 72 children who did not receive a platelet transfusion. No serious adverse events occurred in the one study that reported this outcome (1 study, 21 participants, very low-quality evidence). We found no studies that evaluated all-cause mortality within 30 days from the lumbar puncture procedure, length of hospital stay, proportion of participants who received platelet transfusions, or quality of life. We found no evidence from RCTs or non-randomised studies on which to base an assessment of the correct platelet transfusion threshold prior to insertion of a lumbar puncture needle or epidural catheter. There are no ongoing registered RCTs assessing the effects of different platelet transfusion thresholds prior to the insertion of a lumbar puncture or epidural anaesthesia in people with thrombocytopenia. Any future study would need to be very large to detect a difference in the risk of bleeding. A study would need to be designed with at least 47,030 participants to be able to detect an increase in the number of people who had major procedure-related bleeding from 1 in 1000 to 2 in 1000. The use of a central data collection register or routinely collected electronic records (big data) is likely to be the only method to systematically gather data relevant to this population. | We searched scientific databases for clinical studies of people of any age with low platelet counts requiring a lumbar puncture or epidural anaesthesia. The evidence is current to 13 February 2018. In this review, we found only three cohort studies. Only two of these studies reported outcomes relevant to this review. Both studies included people with low platelet counts and blood cancer; one included 21 adults and the other included 129 children. Both studies compared people who had and had not received platelet transfusions before the insertion of a lumbar puncture needle. No studies assessed the use of platelet transfusions prior to insertion of an epidural catheter or different platelet count thresholds for platelet transfusion administration prior to a procedure. There were no major procedure-related bleeding complications in either study. No serious adverse events occurred in the one study (21 participants) that reported this outcome. There was little or no difference in the number of minor bleeding complications in either adults or children who received or did not receive platelet transfusions. None of the studies reported on death, number of platelet transfusions given after the procedure, length of hospital stay, or quality of life. The quality of the evidence from the included studies was very poor. We found no evidence from randomised controlled trials to answer our review question. A study would need to be designed with at least 47,030 participants to be able to detect an increase in the number of people who had bleeding after lumbar puncture or epidural anaesthetic from 1 in 1000 to 2 in 1000. A study that uses routinely collected electronic medical records (big data) is likely to be the only study design that could answer our review question. |
A total of 11 studies recruiting 5862 apparently healthy adults met the inclusion criteria. All of the studies took place in high-income countries. The effect of the interventions on cardiovascular fitness at one year (two studies; 444 participants) was positive and moderate with significant heterogeneity of the observed effects (SMD 0.40; 95% CI 0.04 to 0.76; high quality evidence). The effect of the interventions on self-reported PA at one year (nine studies; 4547 participants) was positive and moderate (SMD 0.20; 95% CI 0.11 to 0.28; moderate quality evidence) with heterogeneity (I2 = 37%) in the observed effects. One study reported positive results at two years (SMD 0.20; 95% CI 0.08 to 0.32; moderate quality evidence). When studies were stratified by risk of bias, the studies at low risk of bias (eight studies; 3403 participants) had an increased effect (SMD 0.28; 95% CI 0.16 to 0.40; moderate quality evidence). The most effective interventions applied a tailored approach to the type of PA and used telephone contact to provide feedback and to support changes in PA levels. There was no evidence of an increased risk of adverse events (seven studies; 2892 participants). Risk of bias was assessed as low (eight studies; 3060 participants) or moderate (three studies; 2677 participants). There were no differences in effectiveness between studies using different types of professionals delivering the intervention (for example health professional, exercise specialist). There was no difference in pooled estimates between studies that generated the prescribed PA using an automated computer programme versus a human, nor between studies that used pedometers as part of their intervention compared to studies that did not. We found consistent evidence to support the effectiveness of remote and web 2.0 interventions for promoting PA. These interventions have positive, moderate sized effects on increasing self-reported PA and measured cardio-respiratory fitness, at least at 12 months. The effectiveness of these interventions was supported by moderate and high quality studies. However, there continues to be a paucity of cost effectiveness data and studies that include participants from varying socioeconomic or ethnic groups. To better understand the independent effect of individual programme components, longer term studies, with at least one year follow-up, are required. | We included a total of 11 studies recruiting 5862 apparently healthy adults in this review. The findings of the review indicate that using technologies to support adults' attempts to become more active, achieve the recommended weekly amounts of activity, or become fitter are successful. Changes can be achieved with help from a trained professional and through personal support via telephone, e-mail, or written information. New physical activity can be maintained for at least one year and it does not increase the risk of falls or exercise related injuries. More research is needed to establish which methods of exercise promotion encourage specific groups of people to be more physically active in the long term. |
We included two studies with a total of 141 participants (aged 7 to 18 years) with chronic neuropathic pain, complex regional pain syndrome type 1 (CRPS-I), or fibromyalgia. One study investigated pregabalin versus placebo in participants with fibromyalgia (107 participants), and the other study investigated gabapentin versus amitriptyline in participants with CRPS-I or neuropathic pain (34 participants). We were unable to perform any quantitative analysis. Risk of bias for the two included studies varied, due to issues with randomisation (low to unclear risk), blinding of outcome assessors (low to unclear risk), reporting bias (low to unclear risk), the size of the study populations (high risk), and industry funding in the 'other' domain (low to unclear risk). We judged the remaining domains of sequence generation, blinding of participants and personnel, and attrition as low risk of bias. Primary outcomes One study (gabapentin 900 mg/day versus amitriptyline 10 mg/day, 34 participants, for 6 weeks) did not report our primary outcomes. The second study (pregabalin 75 to 450 mg/day versus placebo 75 to 450 mg/day, 107 participants, for 15 weeks) reported no significant change in pain scores for pain relief of 30% or greater between pregabalin 18/54 (33.3%), and placebo 16/51 (31.4%), P = 0.83 (very low-quality evidence). This study also reported Patient Global Impression of Change, with the percentage of participants feeling "much or very much improved" with pregabalin 53.1%, and placebo 29.5% (very low-quality evidence). Secondary outcomes In one small study, adverse events were uncommon: gabapentin 2 participants (2 adverse events); amitriptyline 1 participant (1 adverse event) (6-week trial). The second study reported a higher number of adverse events: pregabalin 38 participants (167 adverse events); placebo 34 participants (132 adverse events) (15-week trial) (very low-quality evidence). Withdrawals due to adverse events were infrequent in both studies: pregabalin (4 participants), placebo (4 participants), gabapentin (2 participants), and amitriptyline (1 participant) (very low-quality evidence). Serious adverse events were reported in both studies. One study reported only one serious adverse event (cholelithiasis and major depression resulting in hospitalisation in the pregabalin group) and the other study reported no serious adverse events (very low-quality evidence). There were few or no data for our remaining secondary outcomes. Quality of evidence For the outcomes with available data, we downgraded the quality of the evidence by three levels to very low-quality due to too few data and the fact that the number of events was too small to be meaningful. This review identified only two small studies, with insufficient data for analysis. As we could undertake no meta-analysis, we were unable to comment about efficacy or harm from the use of antiepileptic drugs to treat chronic non-cancer pain in children and adolescents. Similarly, we could not comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life. We know from adult randomised controlled trials that some antiepileptics, such as gabapentin and pregabalin, can be effective in certain chronic pain conditions. | In September 2016 we searched for clinical trials in which antiepileptic drugs were used to treat chronic pain. We found two studies with a total of 141 participants (aged 7 to 18 years) with chronic neuropathic pain, complex regional pain syndrome type 1, or fibromyalgia, which they had for more than 3 months. One study looked at pregabalin versus placebo for people with fibromyalgia, and found no significant change in pain scores. The other study evaluated gabapentin compared to amitriptyline, but did not report our specified pain outcomes. Side effects were uncommon, and only mild reactions (such as nausea, dizziness, drowsiness, tiredness, and abdominal discomfort): pregabalin 38 participants, gabapentin 2 participants, amitriptyline 1 participant, and placebo 34 participants. Only 11 participants withdrew due to these mild side effects (4 pregabalin, 2 gabapentin, 1 amitriptyline, 4 placebo). We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. The available evidence in this review was of very low-quality due to a lack of data and small study sizes. |
Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective. Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized. | Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born weighing less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants weighing less than 1000 grams at birth. |
We identified 30 RCTs with 9177 participants. Sixteen trials were parallel two-arm RCTs, and seven were three-arm parallel trials. There were also seven cluster-randomised trials: two had four arms, and the remaining five had two arms. The median duration of the intervention was six months (range 1 week to 24 months), and the median follow-up period was 12 months (range 0 to 12 months). The trials included a wide spectrum of interventions and were both individual- and group-based. A meta-analysis of all psychological interventions combined versus usual care showed no firm effect on DRD (standardised mean difference (SMD) -0.07; 95% CI -0.16 to 0.03; P = 0.17; 3315 participants; 12 trials; low-quality evidence), HRQoL (SMD 0.01; 95% CI -0.09 to 0.11; P = 0.87; 1932 participants; 5 trials; low-quality evidence), all-cause mortality (11 per 1000 versus 11 per 1000; risk ratio (RR) 1.01; 95% CI 0.17 to 6.03; P = 0.99; 1376 participants; 3 trials; low-quality evidence) or adverse events (17 per 1000 versus 41 per 1000; RR 2.40; 95% CI 0.78 to 7.39; P = 0.13; 438 participants; 3 trials; low-quality evidence). We saw small beneficial effects on self-efficacy and HbA1c at medium-term follow-up (6 to 12 months): on self-efficacy the SMD was 0.15 (95% CI 0.00 to 0.30; P = 0.05; 2675 participants; 6 trials; low-quality evidence) in favour of psychological interventions; on HbA1c there was a mean difference (MD) of -0.14% (95% CI -0.27 to 0.00; P = 0.05; 3165 participants; 11 trials; low-quality evidence) in favour of psychological interventions. Our included trials did not report diabetes-related complications or socioeconomic effects. Many trials were small and were at high risk of bias for incomplete outcome data as well as possible performance and detection biases in the subjective questionnaire-based outcomes assessment, and some appeared to be at risk of selective reporting. There are four trials awaiting further classification. These are parallel RCTs with cognition-focused and emotion-cognition focused interventions. There are another 18 ongoing trials, likely focusing on emotion-cognition or cognition, assessing interventions such as diabetes self-management support, telephone-based cognitive behavioural therapy, stress management and a web application for problem solving in diabetes management. Most of these trials have a community setting and are based in the USA. Low-quality evidence showed that none of the psychological interventions would improve DRD more than usual care. Low-quality evidence is available for improved self-efficacy and HbA1c after psychological interventions. This means that we are uncertain about the effects of psychological interventions on these outcomes. However, psychological interventions probably have no substantial adverse events compared to usual care. More high-quality research with emotion-focused programmes, in non-US and non-European settings and in low- and middle-income countries, is needed. | We found 30 randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups) with 9177 participants. The duration of the interventions ranged from 1 week to 12 months and follow-up after treatment from 0 to 12 months. Most studies took place in community settings, almost all in high-income countries and two each in Asia and Latin America. The studies included a wide spectrum of interventions and were both individual- and group-based. Psychological interventions have a small and positive effect on confidence for self-care and glycosylated haemoglobin A1c (HbA1c - a long-term measure of glucose control) in adults with type 2 diabetes. Compared to usual care, psychological interventions showed no firm effect on diabetes-related distress, health-related quality of life, death from any cause, adverse events or blood pressure levels. No study reported on diabetes-related complications (like stroke, heart attacks or kidney impairment) or socioeconomic effects (such as absence from work or costs for medication). This evidence is up to date as of 21 September 2016. Overall, the quality of the evidence was low because of small studies, missing data, and limitations in the design and implementation of the included studies. Four studies are awaiting further assessment, and 18 studies are ongoing with results hopefully be published in the near future. |
The primary analysis of overall effect using hazard ratios derived from published survival curves involved six trials (692 women). No significant difference was seen (hazard ratio 0.94, 95% CI 0.79 to 1.12, P = 0.5). A test for heterogeneity gave a P value of 0.1. A pooled estimate of reported response rates in eight trials involving 817 women showed a significant advantage for chemotherapy over endocrine therapy with a relative risk of 1.25 (95% CI 1.01 to 1.54, P = 0.04). However the point estimates for the two largest trials were in opposite directions, and an overall test for heterogeneity gave a P value of 0.0009. There was little information available on toxicity and quality of life. Six of the seven fully published trials commented on increased toxicity with chemotherapy, mentioning nausea, vomiting and alopecia. Three of the seven trials mentioned aspects of quality of life, with differing results. Only one trial formally measured quality of life, concluding that it was better with chemotherapy. In women with metastatic breast cancer and where hormone receptors are present, a policy of treating first with endocrine therapy rather than chemotherapy is recommended except in the presence of rapidly progressive disease. | This review found that while initial treatment with chemotherapy rather than endocrine therapy may be associated with a higher response rate, the two initial treatments had a similar effect on overall survival. No single group of patients who might benefit from or be harmed by one treatment over the other were identified, although there was little information to address this question. Six of the seven fully published trials commented on increased toxicity associated with chemotherapy including nausea, vomiting and alopecia. Three of the seven trials mentioned aspects of quality of life but their findings provided differing results. Only one trial formally measured quality of life (QOL), concluding that QOL was better with chemotherapy. Based on these trials, no conclusions can be made as to the QOL achieved with either treatment. Accurate information about hormone receptor status is now routinely available for many women with metastatic breast cancer, and hormonal treatments have improved in their effectiveness in the last 10 years. In women with metastatic breast cancer where hormone receptors are present, a policy of treating first with endocrine therapy rather than chemotherapy appears to be better, on the basis of the trials and outcomes in this review, except in the presence of rapidly progressive disease. |
We identified one randomised clinical trial eligible for inclusion in this review. This study compared the use of nebulised pentoxifylline versus placebo for prevention of BPD in 100 preterm infants and was at high risk of bias due to lack of blinding of intervention and outcome assessors, and incomplete outcome data. There was no statistically significant effect of nebulised pentoxifylline versus placebo on individual outcomes of BPD at 36 weeks PMA or on death prior to 36 weeks PMA. There was no significant effect of nebulised pentoxifylline on intraventricular haemorrhage, periventricular leukomalacia, sepsis, or patent ductus arteriosus (PDA) requiring ligation. The study did not report any of the other secondary outcomes considered for this review. Reporting of adverse events was very limited and did not allow for reliable judgement on the incidence of such events. No long-term outcomes were reported. There is insufficient evidence to determine the safety and efficacy of pentoxifylline for prevention of BPD in preterm neonates. We encourage researchers to conduct clinical trials to confirm or refute the role of pentoxifylline for prevention of BPD in preterm neonates. These trials should report on clinically important outcomes and, ideally, on long-term neurodevelopmental outcome. | The main aim of this review was to find out whether pentoxifylline compared with placebo (an inactive drug) or no drug offers important advantages to babies born early. Only one study of moderate size and quality was identified in this review. This study did not show strong evidence that pentoxifylline offers important advantages to babies born early. We have therefore been unable to determine the effects of pentoxifylline in preventing long-lasting breathing problems in babies born early. Future high-quality studies are needed to answer this question. |
Three studies (212 participants) were included in this review. The overall risk of bias was high for two trials and unclear for one. One trial (101 participants) compared ozone treatment with antibiotics for foot ulcers in people with DM. The study had a follow-up period of 20 days. This study showed that ozone treatment was associated with a greater reduction in ulcer area from baseline to the end of the study than treatment with antibiotics (MD -20.54 cm2, 95% CI -20.61 to -20.47), and a shorter duration of hospitalisation (MD -8.00 days, 95% CI -14.17 to -1.83), but did not appear to affect the number of ulcers healed over 20 days (RR 1.10, 95% CI 0.87 to 1.40). No side effects were observed in either group. The other two trials (111 participants) compared ozone treatment plus usual care with usual care for foot ulcers in people with DM. The meta-analysis results did not show evidence of a difference between groups for the outcomes of reduction of ulcer area (MD -2.11 cm2, 95% CI -5.29 to 1.07), the number of ulcers healed (RR 1.69, 95% CI 0.90 to 3.17), adverse events (RR 2.27, 95% CI 0.48 to 10.79), or amputation rate (RR 2.73, 95%CI 0.12, 64.42). The available evidence was three small RCTs with unclear methodology, so we are unable to draw any firm conclusions regarding the effectiveness of ozone therapy for foot ulcers in people with DM. | The review authors searched the medical literature up to March 3 2015, and identified three relevant clinical trials (212 participants) that investigated ozone therapy for the treatment of foot ulcers in people with diabetes. The available evidence was of low quality. One trial, with 101 participants, compared ozone treatment with antibiotics and followed up for 20 days. The results of this study showed that the reduction in ulcer size was greater, and also the length of hospital stay was shorter, in those receiving ozone treatment, but there was no apparent benefit in terms of the number of foot ulcers healed. No adverse effects (side effects or harms) were observed with either treatment. The other two trials (111 participants) compared ozone treatment plus usual care with usual care. The results of these two studies showed that there were no apparent differences between the groups for reduction in ulcer size,the number of foot ulcers healed, or occurrence of adverse events and amputation rates. Quality of life was not reported by either trial. On the basis of the limited and poor quality information available, the review authors were unable to draw any conclusions about the effectiveness of ozone therapy for treating foot ulcers in people with DM. |
Seventeen studies were identified in the searches; eight randomised controlled trials were included, recruiting 899 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sβºthalassaemia (HbSβºthal) genotypes). Studies lasted from six to 30 months. Four studies (577 adults and children with HbSS or HbSβºthal) compared hydroxyurea to placebo; three recruited individuals with only severe disease and one recruited individuals with all disease severities. There were statistically significant improvements in terms of pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use), measures of fetal haemoglobin and neutrophil counts and fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups. There were no consistent statistically significant differences in terms of quality of life and adverse events (including serious or life-threatening events). Seven deaths occurred during the studies, but the rates by treatment group were not statistically significantly different. Two studies (254 children with HbSS or HbSβºthal also with risk of primary or secondary stroke) compared hydroxyurea and phlebotomy to transfusion and chelation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts, but more occurrences of acute chest syndrome and infections in the hydroxyurea and phlebotomy group. There were no consistent statistically significant differences in terms of pain alteration and adverse events (including serious or life-threatening events). Two deaths occurred during the studies (one in a the hydroxyurea treatment arm and one in the control arm), but the rates by treatment group were not statistically significantly different. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early. The quality of the evidence for the above two comparisons was judged as moderate to low as the studies contributing to these comparisons were mostly large and well designed (and at low risk of bias); however evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events and results are applicable only to individuals with HbSS and HbSβºthal genotypes. Of the remaining two studies, one (22 children with HbSS or HbSβºthal also at risk of stoke) compared hydroxyurea to observation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts but no statistically significant differences in terms of adverse events (including serious or life-threatening events). The final study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea – there was statistically significant improvement in terms of measures of fetal haemoglobin, but no statistically significant differences in terms of adverse events (including serious or life-threatening events). No participants died in either of these studies and other outcomes relevant to the review were not reported. The quality of the evidence for the above two comparisons was judged to be very low due to the limited number of participants, the lack of statistical power (as both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes. There is evidence to suggest that hydroxyurea is effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSβºthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly in preventing chronic complications of SCD, recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with HbSC genotype. Future studies should be designed to address such uncertainties. | We included eight studies (899 adults and children with SCD (HbSS, HbSC or HbSβºthal genotypes)). Studies lasted from six to 30 months. In four studies, 577 adults and children with SCD were randomly selected to receive hydroxyurea or placebo. In two studies, 254 children with SCD, who were also at an increased risk of having a first or second stroke, were randomly selected to receive hydroxyurea and phlebotomy (collection of blood) or blood transfusion and chelation (administration of agents to remove excess iron from the body). These six studies only recruited people with HbSS or HbSβºthal genotypes so results do not apply to people with the HbSC genotype. There was moderate quality evidence from these six studies that those receiving hydroxyurea experienced significant reductions in the frequency of pain crises, increases in fetal haemoglobin and decreases in neutrophil (white blood cell) counts compared to the comparator treatment. There was no difference between people receiving hydroxyurea or other treatments in terms of quality of life, deaths during the studies and side effects (including serious and life-threatening side effects); however, there is less information about these outcomes in the studies, so the quality of this evidence is low. Two further studies were included in the review. In one study, 22 children with SCD, who were also at an increased risk of having a stroke, were randomly selected to receive hydroxyurea or no treatment (observation only) and in one study 44 adults and children were randomly selected to receive treatments with or without adding hydroxyurea. Both studies showed an increase in fetal haemoglobin for people receiving hydroxyurea compared to the comparator treatment and there were no deaths during the studies. There was no difference between people receiving hydroxyurea or other treatments in terms of pain crises and side effects (including serious or life-threatening side effects) and these studies did not measure quality of life. The quality of the evidence from these studies is very low, given the studies were very small and only recruited around 20% of the intended number of people and results do not apply to all people with SCD (different genotypes). The evidence shows that hydroxyurea is likely to be effective in the short term at decreasing the frequency of painful episodes and raising fetal haemoglobin levels in the blood in people with SCD. Hydroxyurea is also likely to be effective in preventing first strokes for those at an increased risk of stroke and does not seem to be associated with an increase in any side effects (including serious and life-threatening side effects). There is currently not much evidence on whether hydroxyurea is beneficial over a long period of time, what the best dose to take is, or whether treatment causes any long-term or serious side effects. More studies are needed to answer these questions. |
We included one RCT (100 participants) which lasted 52 weeks comparing continuous inhaled aztreonam lysine (AZLI) and placebo in a double-blind RCT for 24 weeks, followed by a 24-week open-label extension and a four-week follow-up period. The average participant age was 26.3 years, 61% were male and average lung function was 56.5% predicted. Treatment with AZLI for 24 weeks was not associated with improvement in forced expiratory volume in one second (FEV1), mean difference 0.91% (95% confidence interval (CI) -3.15 to 4.97) (moderate-quality evidence). The median time to the next exacerbation was 75 days in the AZLI group compared to 51 days in the placebo group, but the difference was not significant (P = 0.27) (moderate-quality evidence). Similarly, the number of participants hospitalised for respiratory exacerbations showed no difference between groups, risk ratio (RR) 0.88 (95% CI 0.53 to 1.45) (moderate-quality evidence). Overall adverse events were similar between groups, RR 1.08 (95% CI 0.98 to 1.19) (moderate-quality evidence). There were no significant differences between treatment groups in relation to mortality (moderate-quality evidence), quality of life or sputum density. In relation to methodological quality, the overall risk of bias in the study was assessed to be unclear to low risk. We found insufficient evidence from the literature to determine an effective strategy for antibiotic therapy for treating chronic BCC infection. | This review included one study of 100 people aged between 6 and 57 years old. The study compared an inhaled antibiotic called aztreonam to placebo (a substance which contains no medication) and people were selected for one treatment or the other randomly (by chance). The study lasted 52 weeks. The only study included in this review found inhaled aztreonam had no beneficial effect on lung function or rates of chest infections in people with cystic fibrosis and Burkholderia cepacia complex infection. There was no difference between groups in relation to the average time to the next exacerbation or the number of people hospitalised for an exacerbation. Overall adverse events were similar between groups and with regards to other outcomes assessed, there was no difference between treatment groups for mortality, quality of life or sputum density. More research is needed to establish if other inhaled antibiotics may be useful. Overall quality of evidence was considered to be moderate across all outcomes, which means further research is likely to have an important impact on results. |
We included 160 studies with 54,109 enrolled participants; 53,713 participants started the studies and 50,034 completed the studies or data analysis (or both). We could not use 115 RCTs in meta-analytic comparisons because they had zero awareness events. We did not merge 27 of the remaining 45 studies because they had excessive clinical and methodological heterogeneity. We pooled the remaining 18 eligible RCTs in meta-analysis. There are 10 studies awaiting classification which we will process when we update the review. The meta-analyses included 18 trials with 36,034 participants. In the analysis of anaesthetic depth monitoring (either Bispectral Index or M-entropy) versus standard clinical and electronic monitoring, there were nine trials with 34,744 participants. The overall event rate was 0.5%. The effect favoured neither anaesthetic depth monitoring nor standard clinical and electronic monitoring, with little precision in the odds ratio (OR) estimate (OR 0.98, 95% confidence interval (CI) 0.59 to 1.62). In a five-study subset of Bispectral Index monitoring versus standard clinical and electronic monitoring, with 34,181 participants, 503 participants gave awareness reports to a blinded, expert panel who adjudicated or judged the outcome for each patient after reviewing the questionnaires: no awareness, possible awareness, or definite awareness. Experts judged 351 patient awareness reports to have no awareness, 87 to have possible awareness, and 65 to have definite awareness. The effect size favoured neither Bispectral Index monitoring nor standard clinical and electronic monitoring, with little precision in the OR estimate for the combination of definite and possible awareness (OR 0.96, 95% CI 0.35 to 2.65). The effect size favoured Bispectral Index monitoring for definite awareness, but with little precision in the OR estimate (OR 0.60, 95% CI 0.13 to 2.75). We performed three smaller meta-analyses of anaesthetic drugs. There were nine studies with 1290 participants. Wakefulness was reduced by ketamine and etomidate compared to thiopental. Wakefulness was more frequent than awareness. Benzodiazepines reduces awareness compared to thiopental, ketamine, and placebo., Also, higher doses of inhaled anaesthetics versus lower doses reduced the risk of awareness. We graded the quality of the evidence as low or very low in the 'Summary of findings' tables for the five comparisons. Most of the secondary outcomes in this review were not reported in the included RCTs. Anaesthetic depth monitors may have similar effects to standard clinical and electrical monitoring on the risk of awareness during surgery. In older studies comparing anaesthetics in a smaller portion of the patient sample, wakefulness occurred more frequently than awareness. Use of etomidate and ketamine lowered the risk of wakefulness compared to thiopental. Benzodiazepines compared to thiopental and ketamine, or higher doses of inhaled anaesthetics versus lower doses, reduced the risk of awareness. | We found 160 randomized controlled trials with 54,109 participants. Eighteen studies with 36,034 participants contributed evidence about devices and drugs to prevent premature waking up during surgery. Nine studies compared anaesthetic depth monitoring versus other methods to adjust drugs. Nine studies compared different drugs. There are 10 studies awaiting classification, which we will process when we update the review. In the largest studies of anaesthetic depth monitors (five studies with 31,181 participants) there were 152 participants with possible or definite awareness (recall of surgery events after surgery). The use of anaesthetic depth monitors to adjust drugs during anaesthesia may have similar effects on the risk of awareness when compared with standard clinical and electrical monitoring. Wakefulness is reduced by ketamine and etomidate compared to thiopental. Benzodiazepines reduces awareness compared to thiopental, ketamine, and placebo. Also higher doses of inhaled anaesthetics versus lower doses reduced the risk of awareness. The quality of the evidence was low or very low because the studies the results were not similar across studies, and there were not enough data. |
We included three small studies with a cross-over design, involving a total of 20 participants (11 adults and 9 children), in this review. Our primary outcome was mortality, and there was one death by the time of follow-up 28 days after hospital admission. The trials did not measure the clinical secondary outcomes of quality of life, GCS, and disability. The included studies provided information only for the secondary outcomes intracranial pressure (ICP), cerebral perfusion pressure (CPP), and adverse effects. We were unable to pool the results as the data were either presented in different formats or no numerical data were provided. We included narrative interpretations of the available data. The overall risk of bias of the studies was unclear due to poor reporting of the methods. There was marked inconsistency across studies for the outcome of ICP and small sample sizes or wide confidence intervals for all outcomes. We therefore rated the quality of the evidence as very low for all outcomes and have not included the results of individual studies here. We do not have enough evidence to draw conclusions about the effect of HBE during intensive care management of people with TBI. The lack of consistency among studies, scarcity of data and the absence of evidence to show a correlation between physiological measurements such as ICP, CCP and clinical outcomes, mean that we are uncertain about the effects of HBE during intensive care management in people with severe TBI. Well-designed and larger trials that measure long-term clinical outcomes are needed to understand how and when different backrest positions can affect the management of severe TBI. | We found three small studies, with a total of 20 people (11 adults and 9 children). The studies had a cross-over design (participants received the study interventions in a random order, and served as their own control) and looked at the effect of different head positions. Researchers measured the pressure inside the skull (intracranial pressure (ICP)) and the pressure gradient causing blood flow to the brain (cerebral perfusion pressure (CPP)). Two studies were funded by research grants from the national Department of Health, and one study received no funding. At the time of follow-up 28 days following hospital admission, one child had died. None of the studies assessed quality of life, Glasgow Coma Scale (a measurement of how conscious someone is), or disability. The studies gave varied results and our certainty in the results is very low, so we do not consider the body of evidence to be reliable. None of the studies found any evidence of a change in CPP due to different backrest positions. The results for ICP were more mixed but there is still no convincing evidence that HBE changes ICP. There is insufficient evidence to say whether the intervention is safe. One child experienced an increase in ICP in response to the intervention, which resolved when the height of the bed was returned to the normal position. We are uncertain about the effects of different backrest positions in people with serious brain injury. The body of evidence for this research question is very low due to variability in physiological response in the study participants, unclear risk of bias in the study methods, and the small number of people enrolled in each study. We are uncertain about the effects of different backrest positions in people with serious brain injury. Well-designed and larger trials are needed. Trials also need to measure the right patient outcomes over a longer period of time in order to understand how and when different backrest positions can affect people with brain injury. |
We included six trials with 1176 adolescents that measured outcomes at different follow-up periods in this review. Three studies with 732 adolescents compared brief interventions (Bls) with information provision only, and three studies with 444 adolescents compared Bls with assessment only. Reasons for downgrading the quality of evidence included risk of bias of the included studies, imprecision, and inconsistency. For outcomes that concern substance abuse, the retrieved studies only assessed alcohol and cannabis. We generally found moderate-quality evidence that, compared to information provision only, BIs did not have a significant effect on any of the substance use outcomes at short-, medium-, or long-term follow-up. They also did not have a significant effect on delinquent-type behaviour outcomes among adolescents. When compared to assessment-only controls, we found low- or very low-quality evidence that BIs reduced cannabis frequency at short-term follow-up in one study (standardised mean difference (SMD) -0.83; 95% confidence interval (CI) -1.14 to -0.53, n = 269). BIs also significantly reduced frequency of alcohol use (SMD -0.91; 95% CI -1.21 to -0.61, n = 242), alcohol abuse (SMD -0.38; 95% CI -0.7 to -0.07, n = 190) and dependence (SMD -0.58; 95% CI -0.9 to -0.26, n = 190), and cannabis abuse (SMD -0.34; 95% CI -0.65 to -0.02, n = 190) at medium-term follow-up in one study. At long-term follow-up, BIs also reduced alcohol abuse (SMD -0.72; 95% CI -1.05 to -0.40, n = 181), cannabis frequency (SMD -0.56; 95% CI -0.75 to -0.36, n = 181), abuse (SMD -0.62; 95% CI -0.95 to -0.29, n = 181), and dependence (SMD -0.96; 95% CI -1.30 to -0.63, n = 181) in one study. However, the evidence from studies that compared brief interventions to assessment-only conditions was generally of low quality. Brief interventions also had mixed effects on adolescents' delinquent or problem behaviours, although the effect at long-term follow-up on these outcomes in the assessment-only comparison was significant (SMD -0.78; 95% CI -1.11 to -0.45). We found low- or very low-quality evidence that brief school-based interventions may be more effective in reducing alcohol and cannabis use than the assessment-only condition and that these reductions were sustained at long-term follow-up. We found moderate-quality evidence that, when compared to information provision, brief interventions probably did not have a significant effect on substance use outcomes. It is premature to make definitive statements about the effectiveness of brief school-based interventions for reducing adolescent substance use. Further high-quality studies examining the relative effectiveness of BIs for substance use and other problem behaviours need to be conducted, particularly in low- and middle-income countries. | We included six studies in this review, with 1176 adolescents overall. The mean age of adolescents was 16.9 years. We were interested in studies with short-, medium-, and long-term follow-up periods to assess whether any effects were due to the brief intervention. The studies compared brief intervention programmes with two major kinds of comparison or control groups: 1) an information provision only (general health promotion materials and harm reduction information) group and 2) an assessment-only group, where adolescents received no intervention but were evaluated on substance use and other behaviour at follow-up appointments at different time periods following delivery of the intervention. Three studies with 732 adolescents compared brief interventions with information provision only, while the other three, with 444 adolescents, compared brief interventions with assessment only. Trials were either conducted in the United States or the United Kingdom. Delivery of the interventions was individual or group face-to-face feedback across high schools and further education colleges. All interventions were up to four sessions in length. Our primary outcome was abstinence or reduction of substance use behaviour, and our secondary outcomes were engagement in criminal activity related to substance use and engagement in delinquent-type behaviours related to substance use. For outcomes that concern substance use, the studies assessed use of alcohol and cannabis. When compared to information provision, brief interventions are probably not more efficacious in reducing substance use or delinquent behaviour. When compared to assessment-only controls, the interventions may have some significant effects on substance use and behaviours. At short-term follow-up, brief interventions significantly reduced cannabis frequency in one study. At medium-term follow-up, brief interventions significantly reduced frequency of alcohol use, alcohol abuse and dependence symptoms, and cannabis abuse symptoms in one study. At long-term follow-up, brief interventions significantly reduced alcohol abuse, cannabis frequency, and cannabis abuse and dependence symptoms in one study. The pattern of results indicates that adolescents who received a brief intervention generally did better in reducing their alcohol and cannabis use than adolescents who received no intervention at all. However, adolescents who received a brief intervention did not seem to do better in reducing their alcohol and cannabis use than adolescents who received information-only interventions. It is therefore premature to make definitive statements about the effectiveness of brief school-based interventions for reducing adolescent substance use. Overall, the evidence was of moderate or low quality, with two outcomes found to have very low quality of evidence. There were three major issues across the studies: 1) there was no blinding of adolescents, 2) there was uncertainty as to whether participant allocation to study groups was concealed, and 3) a small total number of adolescents and number of events. None of the included studies reported information about funding source or conflicts of interest. |
Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized. Four studies reported the responses to enzyme replacement therapy of previously untreated individuals with type 1 Gaucher disease. Two studies investigated maintenance enzyme replacement therapy in people with stable type 1 Gaucher disease previously treated for at least two years. One study compared substrate reduction therapy, enzyme replacement therapy and a combination thereof as maintenance therapy in people with type 1 Gaucher disease previously treated with enzyme replacement therapy. One study examined substrate reduction therapy in people with chronic neuronopathic (type 3) Gaucher disease who continued to receive enzyme replacement therapy. Treatment-naïve participants had similar increases in haemoglobin when comparing those receiving imiglucerase or alglucerase at 60 units/kg, imiglucerase or velaglucerase alfa at 60 U/kg, taliglucerase alfa at 30 units/kg or 60 units/kg, and velaglucerase alfa at 45 units/g or 60 units/kg. For platelet count response in participants with intact spleens, a benefit for imiglucerase over velaglucerase alfa at 60 units/kg was observed, mean difference -79.87 (95% confidence interval -137.57 to -22.17). There were no other significant differences in platelet count response when comparing different doses of velaglucerase alfa and of taliglucerase alfa, and when comparing imiglucerase to alglucerase. Spleen and liver volume reductions were not significantly different in any enzyme replacement therapy product or dose comparison study. Although a dose effect on serum biomarkers was not seen after nine months, a significantly greater reduction with higher dose was reported after 12 months in the velaglucerase study, mean difference 16.70 (95% confidence intervaI 1.51 to 31.89). In the two enzyme replacement therapy maintenance studies comparing infusions every two weeks and every four weeks, there were no significant differences in haemoglobin concentration, platelet count, and spleen and liver volumes over a 6 to 12 month period when participants were treated with the same cumulative dose. A total of 25 serious adverse events were reported, nearly all deemed unrelated to treatment. There are, as yet, no randomized trials of substrate reduction therapy in treatment-naïve patients that can be evaluated. Miglustat monotherapy appeared as effective as continued enzyme replacement therapy for maintenance of hematological, organ and biomarker responses in people with type 1 Gaucher disease previously treated with imiglucerase for at least two years. In those with neuronopathic Gaucher disease, no significant improvements in haemoglobin concentration, platelet count or organ volumes occurred when enzyme replacement therapy was augmented with miglustat. One randomized controlled study assessing substrate reduction therapy was published immediately prior to producing the final version of this review, and this, along with a further ongoing study (expected to be published in the near future), will be assessed for eligibility in a future update of the review. The results reflect the limitations of analysing evidence restricted to prospective randomized controlled trials, especially when dealing with chronic rare diseases. This analysis suggests that, during the first year of treatment, different recombinant glucocerebrosidases are bio-similar and non-inferior in safety and efficacy for surrogate biological response parameters. Enzyme replacement therapy given at 30 to 45 units/kg body weight every two to four weeks was generally as effective as the 60 unit/kg dose for the assessed clinical outcomes. The analysis emphasise the need to determine whether it is realistic to carry out multi-decade prospective clinical trials for rare diseases such as type 1 Gaucher disease. With large treatment effects on the classical manifestations of the disorder, therapeutic investigations in Gaucher disease mandate innovative trial designs and methodology to secure decisive data concerning long-term efficacy and safety – with the realization that knowledge about disease-modifying actions that are sustained are of crucial importance to people with this chronic condition. | Although there are many published studies about treatment of Gaucher disease, those that are based on randomized controlled clinical studies are considered to provide the strongest evidence. Eight such studies (300 participants) were identified by systematically reviewing the medical literature. Potential risks of bias in the methods employed in the original studies and in the data reported were assessed; only one study scored 'low' in all bias domains. Six evaluated the possible beneficial effects on the disease by enzyme replacement therapy using different products, doses or frequencies of administration; two studies examined the effects of substrate reduction therapy. Owing to different study methods and data formats, the original results could not be pooled or combined in order to obtain summary measures of efficacy. Our analysis, despite being limited by the small number of studies, suggests that, at least during the first year of treatment, different enzyme replacement therapy drugs appear to have a similar safety profile and all improve some of the most obvious manifestations of the disease. One randomized controlled study assessing substrate reduction therapy was published immediately prior to producing the final version of this review, and this, along with a further ongoing study (expected to be published in the near future), will be assessed for eligibility in a future update of the review. |
We identified 39 trials with 1827 participants. We considered the trials to be at a mixed risk of bias as the result of unreported allocation concealment and probable detection bias. Compared with no intervention, physiotherapy significantly improved the gait outcomes of speed (mean difference 0.04 m/s, 95% confidence interval (CI) 0.02 to 0.06, P = 0.0002); two- or six-minute walk test (13.37 m, 95% CI 0.55 to 26.20, P = 0.04) and Freezing of Gait questionnaire (-1.41, 95% CI -2.63 to -0.19, P = 0.02); functional mobility and balance outcomes of Timed Up & Go test (-0.63 s, 95% CI -1.05 to -0.21, P = 0.003), Functional Reach Test (2.16 cm, 95% CI 0.89 to 3.43, P = 0.0008), and Berg Balance Scale (3.71 points, 95% CI 2.30 to 5.11, P < 0.00001); and clinician-rated disability using the Unified Parkinson’s Disease Rating Scale (UPDRS) (total -6.15 points, 95% CI-8.57 to -3.73, P < 0.00001; activities of daily living: -1.36, 95% CI -2.41 to -0.30, P = 0.01; and motor: -5.01, 95% CI -6.30 to -3.72, P < 0.00001). No difference between arms was noted in falls (Falls Efficacy Scale: -1.91 points, 95% CI -4.76 to 0.94, P = 0.19) or patient-rated quality of life (PDQ-39 Summary Index: -0.38 points, 95% CI -2.58 to 1.81, P = 0.73). One study reported that adverse events were rare; no other studies reported data on this outcome. Indirect comparisons of the different physiotherapy interventions revealed no evidence that the treatment effect differed across physiotherapy interventions for any of the outcomes assessed. Benefit for physiotherapy was found in most outcomes over the short term (i.e. < 3 months) but was significant only for speed, two- or six-minute walk test, Freezing of Gait questionnaire, Timed Up & Go, Functional Reach Test, Berg Balance Scale, and clinician-rated UPDRS. Most of the observed differences between treatments were small. However, for some outcomes (e.g. speed, Berg Balance Scale, UPDRS), the differences observed were at, or approaching, what are considered minimal clinically important changes. These benefits should be interpreted with caution because the quality of most of the included trials was not high. Variation in measurements of outcome between studies meant that our analyses include a small proportion of the participants recruited. This review illustrates that a wide range of approaches are employed by physiotherapists to treat patients with PD. However, no evidence of differences in treatment effect was noted between the different types of physiotherapy interventions being used, although this was based on indirect comparisons. A consensus menu of 'best practice' physiotherapy is needed, as are large, well-designed randomised controlled trials undertaken to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD. | Only randomised controlled trials were included in this review. In these studies,a group of participants were given physiotherapy intervention and were compared with another group of participants, who did not receive physiotherapy. Participants were assigned to a group in random fashion so a fair test was established. Thirty-nine randomised trials involving 1827 participants were identified as suitable for this review. The quality of the trials was not high because in many, methods were not reported adequately and blinding was not feasible. These trials assessed various physiotherapy interventions, so the trials were grouped according to the type of intervention being used (i.e. general physiotherapy, exercise, treadmill training, cueing, dance, or martial arts). Improvement in all walking outcomes (except the 10- or 20-metre walk test) was noted with physiotherapy intervention. However, these improvements were significant only for walking speed, walking endurance, and freezing of gait. Mobility and balance also improved with a physiotherapy intervention, with significant improvements reported in one test of mobility (the Timed Up & Go test, which times how long it takes a person to get up from a chair, walk a certain distance, then walk back to the chair and sit down) and in two tests of balance (one assessing how far a person can reach before he or she loses balance (Functional Reach Test) and another assessing multiple aspects of balance (Berg Balance Scale)). Clinician-rated disability, using the Unified Parkinson’s Disease Rating Scale (UPDRS), was also improved with physiotherapy intervention. No difference was observed between the two groups in falls or patient-rated quality of life. One study reported that adverse events were rare; no other studies reported data on this outcome. When the different physiotherapy interventions were compared, no evidence suggested that treatment effect differed across the physiotherapy interventions for any of the outcomes assessed. This review provides evidence of the short-term benefit of physiotherapy for the treatment of PD. Although most observed differences were small, improvements in walking speed, balance with the Berg Balance Scale, and clinician-rated disability using the UPDRS were of a size that patients may consider them to be important. These benefits should be interpreted with caution because of the quality of the included trials, and the lack of common assessment of treatment effects. This affected the quantity of data that we could use for analysis. |
We identified three studies involving 433 patients. Overall, the quality of studies was not high, and there was moderate to high risk of bias. Interventions of a pre-visit booklet and a pre-visit session (either combined or pre-visit session alone) led to more questioning behaviour and more self-reported active behaviour in the intervention group (3 studies). One study (booklet and pre-visit session) showed no difference in consultation length and time engaged in talk between the intervention and control groups. The booklet and pre-visit session in one study was associated with more satisfaction with interpersonal aspects of care for the intervention group although no difference in overall satisfaction between intervention and control. There was no long-term follow up to see if effects were sustained. No studies measured outcomes relating to the use of health care, health status and wellbeing, or health behaviour. Overall this review shows some positive effects of specific methods to improve the involvement of older people in primary care episodes. Because the evidence is limited, however, we can not recommend the use of the reviewed interventions in daily practice. There should be a balance between respecting patients' autonomy and stimulating their active participation in health care. Face-to-face coaching sessions, whether or not complemented with written materials, may be the way forward. As this is impractical for the whole population, it could be worthwhile to identify a subgroup of older patients who might benefit the most from enhanced involvement, ie. those who want to be involved, but lack the necessary skills. This group could be coached either individually or, more practically, in group sessions. | Therefore we reviewed studies of interventions to improve older people's involvement in their care. There has been little research in this area involving older people as the main target of the research. Only three trials were identified. These evaluated the effects of written or face-to-face preparation for consultations with doctors. Interventions of a pre-visit booklet and a pre-visit session (either combined or pre-visit session alone) led to more questioning behaviour by older people and more self-reported active behaviour. Overall, there is sparse evidence about the effects of interventions for improving older patients' involvement in their primary care. |
We included three randomized controlled trials (RCTs) and one cluster-RCT (with a total of 26,742 participants analysed). We identified one ongoing study. While predominantly adult patients, one study included children. Untrained bystander-administered CPR Three studies assessed CPR provided by untrained bystanders in urban areas of the USA, Sweden and the UK. Bystanders administered CPR under telephone instruction from emergency services. There was an unclear risk of selection bias in two trials and low risk of detection, attrition, and reporting bias in all three trials. Survival outcomes were unlikely to be affected by the unblinded design of the studies. We found high-quality evidence that continuous chest compression CPR without rescue breathing improved participants’ survival to hospital discharge compared with interrupted chest compression with pauses for rescue breathing (ratio 15:2) by 2.4% (14% versus 11.6%; RR 1.21, 95% confidence interval (CI) 1.01 to 1.46; 3 studies, 3031 participants). One trial reported survival to hospital admission, but the number of participants was too low to be certain about the effects of the different treatment strategies on survival to admission(RR 1.18, 95% CI 0.94 to 1.48; 1 study, 520 participants; moderate-quality evidence). There were no data available for survival at one year, quality of life, return of spontaneous circulation or adverse effects. There was insufficient evidence to determine the effect of the different strategies on neurological outcomes at hospital discharge (RR 1.25, 95% CI 0.94 to 1.66; 1 study, 1286 participants; moderate-quality evidence). The proportion of participants categorized as having good or moderate cerebral performance was 11% following treatment with interrupted chest compression plus rescue breathing compared with 10% to 18% for those treated with continuous chest compression CPR without rescue breathing. CPR administered by a trained professional In one trial that assessed OHCA CPR administered by emergency medical service professionals (EMS) 23,711 participants received either continuous chest compression CPR (100/minute) with asynchronous rescue breathing (10/minute) or interrupted chest compression with pauses for rescue breathing (ratio 30:2). The study was at low risk of bias overall. After OHCA, risk of survival to hospital discharge is probably slightly lower for continuous chest compression CPR with asynchronous rescue breathing compared with interrupted chest compression plus rescue breathing (9.0% versus 9.7%) with an adjusted risk difference (ARD) of -0.7%; 95% CI (-1.5% to 0.1%); moderate-quality evidence. There is high-quality evidence that survival to hospital admission is 1.3% lower with continuous chest compression CPR with asynchronous rescue breathing compared with interrupted chest compression plus rescue breathing (24.6% versus 25.9%; ARD -1.3% 95% CI (-2.4% to -0.2%)). Survival at one year and quality of life were not reported. Return of spontaneous circulation is likely to be slightly lower in people treated with continuous chest compression CPR plus asynchronous rescue breathing (24.2% versus 25.3%; -1.1% (95% CI -2.4 to 0.1)), high-quality evidence. There is high-quality evidence of little or no difference in neurological outcome at discharge between these two interventions (7.0% versus 7.7%; ARD -0.6% (95% CI -1.4 to 0.1). Rates of adverse events were 54.4% in those treated with continuous chest compressions plus asynchronous rescue breathing versus 55.4% in people treated with interrupted chest compression plus rescue breathing compared with the ARD being -1% (-2.3 to 0.4), moderate-quality evidence). Following OHCA, we have found that bystander-administered chest compression-only CPR, supported by telephone instruction, increases the proportion of people who survive to hospital discharge compared with conventional interrupted chest compression CPR plus rescue breathing. Some uncertainty remains about how well neurological function is preserved in this population and there is no information available regarding adverse effects. When CPR was performed by EMS providers, continuous chest compressions plus asynchronous rescue breathing did not result in higher rates for survival to hospital discharge compared to interrupted chest compression plus rescue breathing. The results indicate slightly lower rates of survival to admission or discharge, favourable neurological outcome and return of spontaneous circulation observed following continuous chest compression. Adverse effects are probably slightly lower with continuous chest compression. Increased availability of automated external defibrillators (AEDs), and AED use in CPR need to be examined, and also whether continuous chest compression CPR is appropriate for paediatric cardiac arrest. | We included four studies; three compared the two approaches to resuscitation when given by untrained bystanders under instruction by telephone. One study compared the two approaches when given by EMS personnel. The three studies, comparing the approaches given by untrained bystanders, (3737 participants) were all undertaken in urban areas and some included both children and adult OHCA. The, bystanders were all untrained and given telephone instructions from the emergency services. The fourth study compared approaches given by EMS professionals (23,711 participants); it was undertaken in urban areas and included only adult OHCA. When CPR was performed by bystanders, we found that more people survived until discharge from hospital after chest compression alone than they did following interrupted chest compression with pauses at a fixed ratio for rescue breathing (15 compressions to 2 breaths) (14% versus 11.6%). For the outcomes of survival to hospital admission and neurological outcomes, we did not have sufficient data to be certain that either strategy was better. No data was available for adverse effects, quality of life or survival at one-year. When CPR was performed by EMS professionals, we found that survival to hospital discharge was slightly lower with continuous chest compressions (100/minute) plus asynchronous rescue breathing (10/minutes) CPR compared with interrupted chest compression plus rescue breathing. Around 9.7% of people lived when they received interrupted chest compression plus rescue breathing compared with 9% of people who received continuous chest compression plus asynchronous rescue breathing. The number of people who survived to hospital admission was slightly higher in those treated with interrupted chest compression plus rescue breathing compared with continuous chest compression plus asynchronous rescue breathing (25.9% versus 24.6%). There was little or no difference in neurological outcomes. The proportion of people who experienced adverse events was probably similar with 55.4% people treated with interrupted chest compression plus rescue breathing experiencing an adverse event compared with 54.4% in those treated with continuous chest compression asynchronous rescue breathing. For bystander-provided CPR, the quality of the evidence was high for the outcome of survival to hospital discharge. For survival to hospital admission, one trial provided results and the evidence was of moderate-quality because of low numbers of people for whom data were available. This was also the case for neurological outcomes. In the one EMS professional-provided CPR trial, the quality of the evidence was moderate for the outcome of survival to hospital discharge because the results do not exclude there being little or no difference between the two approaches, and this is also the case for adverse events. For survival to hospital admission there was high-quality evidence. The main limitation of the current evidence is that only a few trials have been undertaken, and for some outcomes, not enough data have been generated. |
A total of 29 trials (5489 patients) including 18 comparisons with placebo and 17 comparisons with synthetic standard antidepressants met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In nine larger trials the combined response rate ratio (RR) for hypericum extracts compared with placebo was 1.28 (95% confidence interval (CI), 1.10 to 1.49) and from nine smaller trials was 1.87 (95% CI, 1.22 to 2.87). Results of trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), respectively, RRs were 1.02 (95% CI, 0.90 to 1.15; 5 trials) and 1.00 (95% CI, 0.90 to 1.11; 12 trials). Both in placebo-controlled trials and in comparisons with standard antidepressants, trials from German-speaking countries reported findings more favourable to hypericum. Patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants (odds ratio (OR) 0.24; 95% CI, 0.13 to 0.46) or SSRIs (OR 0.53, 95% CI, 0.34-0.83). The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation. | We have reviewed 29 studies in 5489 patients with depression that compared treatment with extracts of St. John's wort for 4 to 12 weeks with placebo treatment or standard antidepressants. The studies came from a variety of countries, tested several different St. John's wort extracts, and mostly included patients suffering from mild to moderately severe symptoms. Overall, the St. John's wort extracts tested in the trials were superior to placebo, similarly effective as standard antidepressants, and had fewer side effects than standard antidepressants. However, findings were more favourable to St. John's wort extracts in studies form German-speaking countries where these products have a long tradition and are often prescribed by physicians, while in studies from other countries St. John's wort extracts seemed less effective. This differences could be due to the inclusion of patients with slightly different types of depression, but it cannot be ruled out that some smaller studies from German-speaking countries were flawed and reported overoptimistic results. Patients suffering from depressive symptoms who wish to use a St. John's wort product should consult a health professional. Using a St. John's wort extract might be justified, but important issues should be taken into account: St. John's wort products available on the market vary to a great extent. The results of this review apply only to the preparations tested in the studies included, and possibly to extracts with similar characteristics. Side effects of St. John's wort extracts are usually minor and uncommon. However, the effects of other drugs might be significantly compromised. |
Ten RCTs with 1378 women were identified. Of the seven RCTs on group psychological interventions, three were on cognitive behavioural therapy and four were on supportive-expressive group therapy. The remaining three studies were individual based and the types of psychological interventions were not common to either cognitive behavioural or supportive-expressive therapy. A clear pattern of psychological outcomes could not be discerned as a wide variety of outcome measures and durations of follow-up were used in the included studies. The overall effect of the psychological interventions across six studies, on one-year survival, favoured the psychological intervention group with an odds ratio (OR) of 1.46 (95% confidence interval (CI) 1.07 to 1.99). Pooled data from four studies did not show any survival benefit at five-years follow-up (OR 1.03, 95% CI 0.42 to 2.52). There was evidence of a short-term benefit for some psychological outcomes and improvement in pain scores. Psychological interventions appear to be effective in improving survival at 12 months but not at longer-term follow-up, and they are effective in reducing psychological symptoms only in some of the outcomes assessed in women with metastatic breast cancer. However, findings of the review should be interpreted with caution as there is a relative lack of data in this field, and the included trials had reporting or methodological weaknesses and were heterogeneous in terms of interventions and outcome measures. | This review examined the studies to date to see what effect psychological treatments had on women with metastatic breast cancer. We found 10 studies with a total of 1378 women with metastatic breast cancer. Three of the studies used a psychological treatment known as cognitive behavioural therapy (CBT), four studies used supportive-expressive group therapy (SEGT), while the remaining three studies used treatments that were delivered on an individual basis and were neither CBT nor SEGT. We performed statistical analysis and found that the odds ratio (a measure of association between an intervention and an outcome) for survival of women with metastatic breast cancer one year after receiving psychological treatment was 1.46, suggesting that there was an association between the psychological treatment and improved survival. This finding was not found when looking at the odds ratio of survival at five years. We also found some evidence that psychological treatments in the short term (for example, one year) may produce a small reduction in pain and improve some psychological symptoms. However, making comparisons across these studies was difficult as they differed in their conduct, treatments and measures used. Moreover, we cannot rule out that the psychological treatments could also cause psychological harm. |
Eight trials evaluated ursodeoxycholic acid versus placebo or no intervention (592 patients). The eight randomised clinical trials have a high risk of bias. Patients were treated for three months to six years (median three years). The dosage of ursodeoxycholic acid used in the trials ranged from low (10 mg/kg body weight/day) to high (28 to 30 mg/kg body weight/day). Ursodeoxycholic acid did not significantly reduce the risk of death (RR 1.00; 95% CI 0.46 to 2.20); treatment failure including liver transplantation, varices, ascites, and encephalopathy (RR 1.22; 95% CI 0.91 to 1.64); liver histological deterioration (RR 0.89; 95% CI 0.45 to 1.74); or liver cholangiographic deterioration (RR 0.60; 95% CI 0.23 to 1.57). Ursodeoxycholic acid significantly improved serum bilirubin (MD -14.6 µmol/litre; 95% CI -18.7 to -10.6), alkaline phosphatases (MD -506 IU/litre; 95% CI -583 to -430), aspartate aminotransferase (MD -46 IU/litre; 95% CI -77 to -16), and gamma-glutamyltranspeptidase (MD -260 IU/litre; 95% CI -315 to -205), but not albumin (MD -0.20 g/litre; 95% CI -1.91 to 1.50). Ursodeoxycholic acid was safe and well tolerated by patients with primary sclerosing cholangitis. We did not find enough evidence to support or refute the use of bile acids in the treatment of primary sclerosing cholangitis. However, bile acids seem to lead to a significant improvement in liver biochemistry. Therefore, more randomised trials are needed before any of the bile acids can be recommended for this indication. | Based on eight randomised clinical trials of high risk of bias, the administration of ursodeoxycholic acid to patients with primary sclerosing cholangitis did not significantly reduce mortality, hepatic decompensation, need for liver transplantation, liver histological deterioration, or radiological deterioration compared with placebo or no intervention. The use of ursodeoxycholic acid showed a statistically significant improvement of liver biochemistry. However, evidence of these beneficial effects is weak as it is produced from trials with high risk of bias and a rather small number of patients. Furthermore, these observations are at risk of outcome measure reporting bias as half or less than half of the trials reported on these outcomes. One trial assessed the self-estimated quality of life of patients with primary sclerosing cholangitis treated with ursodeoxycholic acid. No significant difference was found in any of the studied components, physical as well as mental. Based on an analysis of six of the eight included trials, the use of ursodeoxycholic acid seemed safe and well tolerated, without reports of serious adverse events. We were unable to identify trials evaluating other bile acids for patients with primary sclerosing cholangitis. Accordingly, the evidence does neither support nor refute bile acids for primary sclerosing cholangitis. |
We included 11 trials in the review, involving a total of 5974 participants. Four trials involving 4701 women compared weight loss programmes with a control intervention. Low quality evidence from one trial suggested that more women following weight loss programmes reported improvement in symptoms of incontinence at six months (163/214 (76%) versus 49/90 (54%), risk ratio (RR) 1.40, 95% confidence interval (CI) 1.14 to 1.71), and this effect was sustained at 18 months (N = 291, 75% versus 62%, RR not estimable, reported P value 0.02). No data were available for self-reported cure and quality of life. One of the weight loss trials involving 1296 women reported very low quality evidence for a reduction in weekly urinary incontinence a mean of 2.8 years after following a lifestyle weight loss intervention that had been compared with a pharmacological weight loss intervention. Three trials involving 181 women and 11 men compared change in fluid intake with no change. Limited, very low quality evidence suggested that symptom-specific quality of life scores improved when fluid intake was reduced, although some people reported headaches, constipation or thirst. A further three trials involving 160 women and nine men compared reduction in caffeinated drinks with no change, and one trial involving 42 women compared a soy-rich diet with soy-free diet. However, it was not possible to reach any conclusions about the effects of these changes, due to methodological limitations, that resulted in very low quality evidence. Adverse effects appeared relatively uncommon for all interventions studied. All included studies had a high or unclear risk of bias across all bias parameters, but most notably for allocation concealment. The main factors for our downgrading of the evidence were risk of bias, indirect evidence (less than 12 months of follow-up; and not all participants having confirmed urinary incontinence at baseline in some studies), and imprecise results with wide confidence intervals. Other interventions such as reduction in consumption of sweetened fizzy or diet drinks; reduction in alcohol consumption; avoiding constipation; smoking cessation; restricting strenuous physical forces; or reducing high levels of, or increasing low levels of, physical activity, could not be assessed in this review, as no evidence from randomized controlled trials or quasi-randomised trials was available. Evidence for the effect of weight loss on urinary incontinence is building and should be a research priority. Generally, there was insufficient evidence to inform practice reliably about whether lifestyle interventions are helpful in the treatment of urinary incontinence. | We (a team of Cochrane researchers) wanted to see whether lifestyle interventions have a beneficial effect on any type of urinary incontinence in adults We searched the medical literature extensively up to July 2013 for studies that compared the effects of community-based lifestyle alterations with either no treatment, or other non-surgical treatments, or medical (medicine) treatment, on urinary incontinence in adults. We identified 11 studies, with 5974 participants (nearly all women, only 20 were men), that investigated the effect of lifestyle alterations on urinary incontinence. Four investigated weight loss; one compared a soy-rich diet with a soy-free diet; three investigated changes in volume of fluid intake; and three investigated the effect of reducing caffeine intake. We identified no trials that investigated reducing alcohol intake, avoiding constipation and straining, stopping smoking or levels of physical activity. Findings from four studies suggested that weight loss may reduce incontinence among overweight women and this merits further research. However, it should be noted that a large proportion of the participants contributing to this result were part of two diabetes studies that, while they recorded the effect of weight loss on urinary incontinence, did not record how many participants suffered from it at the start of the study. The duration of the weight loss programmes in these studies ranged from three to 12 months. A small amount of very low quality evidence from the studies that investigated volume of fluid intake suggested that symptoms of urinary incontinence may reduce when fluid intake is reduced, although some participants in the studies reported headaches, constipation or thirst. We could not combine the findings from other studies that investigated a similar treatment (e.g. caffeine reduction) because they measured their results in different ways, and/or were of poor quality, which means their results may be unreliable. Much more well-designed research is needed, so that lifestyle recommendations for the treatment of incontinence can be based on good evidence. At present there is not enough evidence to establish whether any lifestyle treatments work. |
We found only one quasi-randomised trial with 30 participants that met our inclusion criteria. In the small trial, total and ionised serum calcium levels were measured immediately before and immediately after EBT. All the participants were included in the final analysis and all the important outcomes were reported. Primary outcomes There was one death in each group (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1). The study did not report the presence of cardiac arrhythmias within one week of EBT and the number of infants with serum calcium levels (total less than 8 mg/dL (2 mmol/L) or ionised less than 4.4 mg/dL (1.1 mmol/L)). Pair-wise comparison of EBT with intravenous 10% calcium gluconate versus EBT without intravenous calcium (change from baseline) showed mean total serum calcium was raised in the intervention group compared to the control group (MD -0.46, 95% CI -0.81 to -0.11; participants = 30; studies = 1). Very low-quality evidence also indicated an increase in the levels of mean ionised serum calcium in the intervention group compared to the control group (MD -0.22, 95% CI -0.33 to -0.11; participants = 30; studies = 1). Secondary outcomes Adverse reactions to intravenous calcium therapy included cardiac arrest in one neonate in the intervention arm (RR 3.00, 95% CI 0.13 to 68.26; RD 0.07, 95% CI -0.10 to 0.23; participants = 30; studies = 1). There was apnoea and hypoglycaemia (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1) in the two neonates who died. Data were not available for other major secondary outcomes such as the number of infants with reduced serum magnesium, reduced parathormone, increased calcitonin, presence of seizures, carpopedal spasm, jitteriness and prolonged QTc interval on electrocardiography within one week of EBT. Very low-quality data from one quasi-randomised controlled trial suggested that the mean serum total and ionised calcium increased in the study group but decreased in the control group immediately after EBT. However, the mean values of total and ionised calcium in both arms of studies remained within international reference ranges. Unfortunately, data were not available to assess the trend of total and ionised serum calcium to the end of the first week after EBT. Therefore, due to the very low quality of evidence available, it is difficult to support or reject the continual use of prophylactic intravenous calcium in newborn infants receiving EBT. Researchers are encouraged to conduct more robustly designed trials with larger numbers of participants, and particularly, addressing the pattern of differences based on gestational age of participants, type of anticoagulant used, and the volume of blood used. | we identified only one poorly designed study for inclusion. we found that giving calcium to newborn infants raised blood calcium levels immediately after EBT while blood calcium was reduced among newborn infants who did not receive calcium during EBT. However, despite the observed trends in the values of blood calcium in both groups of the study, the average values of blood calcium in both groups remained within normal limits. In addition, the information available for this review was limited as the effects of giving or not giving calcium during EBT was not studied beyond the time of EBT. based on the findings in this review, there is no good-quality evidence to support or reject continual use of calcium during EBT. We are unable to make conclusions, as the evidence that we found is limited and of very low quality and could change if more results from larger and better-designed studies become available. |
Eight controlled trials (seven placebo controlled and one trial against an active treatment) with a total of 664 participants met the inclusion criteria. Three studied adverse effects of radiotherapy, three studied adverse effects of chemotherapy and two studied menopausal symptoms associated with breast cancer treatment. Two studies with low risk of bias demonstrated benefit: one with 254 participants demonstrated superiority of topical calendula over trolamine (a topical agent not containing corticosteroids) for prevention of radiotherapy-induced dermatitis, and another with 32 participants demonstrated superiority of Traumeel S (a proprietary complex homeopathic medicine) over placebo as a mouthwash for chemotherapy-induced stomatitis. Two other studies reported positive results, although the risk of bias was unclear, and four further studies reported negative results. No serious adverse effects or interactions were reported attributable to the homeopathic medicines used. This review found preliminary data in support of the efficacy of topical calendula for prophylaxis of acute dermatitis during radiotherapy and Traumeel S mouthwash in the treatment of chemotherapy-induced stomatitis. These trials need replicating. There is no convincing evidence for the efficacy of homeopathic medicines for other adverse effects of cancer treatments. Further research is required. | This review looked at whether these medicines could help patients with problems caused by cancer treatments. Eight studies with a total of 664 participants were included in this review. Three studied adverse effects of radiotherapy, three studied adverse effects of chemotherapy and two studied menopausal symptoms associated with breast cancer treatment. Two studies with low risk of bias demonstrated benefit: one with 254 participants demonstrated benefits from calendula ointment in the prevention of radiotherapy-induced dermatitis, and another with 32 participants demonstrated benefits from Traumeel S (a complex homeopathic medicine) over placebo as a mouthwash for chemotherapy-induced stomatitis. These trials need replicating. Two other studies reported positive results, although the risk of bias was unclear, and four further studies reported negative results. The homeopathic medicines used in all eight studies did not seem to cause any serious adverse effects or interact with conventional treatment. No cancer treatments were modified or stopped because of the homeopathic interventions. |
Seven studies, covering 1624 participants, met the inclusion criteria. All included studies investigated adults and compared dexmedetomidine with traditional sedatives, including propofol, midazolam and lorazepam. Compared with traditional sedatives, dexmedetomidine reduced the geometric mean duration of mechanical ventilation by 22% (95% CI 10% to 33%; four studies, 1120 participants, low quality evidence), and consequently the length of stay in the intensive care unit (ICU) by 14% (95% CI 1% to 24%; five studies, 1223 participants, very low quality evidence). There was no evidence that dexmedetomidine decreased the risk of delirium (RR 0.85; 95% CI 0.63 to 1.14; seven studies, 1624 participants, very low quality evidence) as results were consistent with both no effect and appreciable benefit. Only one study assessed the risk of coma, but lacked methodological reliability (RR 0.69; 95% CI 0.55 to 0.86, very low quality evidence). Of all the adverse events included, the most commonly reported one was bradycardia, and we observed a doubled (111%) increase in the incidence of bradycardia (RR 2.11; 95% CI 1.39 to 3.20; six studies, 1587 participants, very low quality evidence). Our meta-analysis provided no evidence that dexmedetomidine had any impact on mortality (RR 0.99; 95% CI 0.79 to 1.24; six studies, 1584 participants, very low quality evidence). We observed high levels of heterogeneity in risk of delirium (I² = 70%), but due to the limited number of studies we were unable to determine the source of heterogeneity through subgroup analyses or meta-regression. We judged six of the seven studies to be at high risk of bias. In this review, we found no eligible studies for children or for clonidine. Compared with traditional sedatives, long-term sedation using dexmedetomidine in critically ill adults reduced the duration of mechanical ventilation and ICU length of stay. There was no evidence for a beneficial effect on risk of delirium and the heterogeneity was high. The evidence for risk of coma was inadequate. The most common adverse event was bradycardia. No evidence indicated that dexmedetomidine changed mortality. The general quality of evidence ranged from very low to low, due to high risks of bias, serious inconsistency and imprecision, and strongly suspected publication bias. Future studies could pay more attention to children and to using clonidine. | We searched the databases until October 2014. We included seven randomized controlled trials, with a total of 1624 participants, comparing dexmedetomidine versus traditional sedatives. All the studies required participants to have an anticipated need for sedation of more than 24 hours. The alternative sedatives included propofol, midazolam and lorazepam. We found no eligible studies in children or for clonidine. Of the seven studies, six were funded by the drug manufacturer, and one did not state any conflict of interest. Compared with traditional sedatives, dexmedetomidine reduced the breathing support time by approximately one-fifth, and the length of stay time in ICU by one-seventh. Dexmedetomidine was at least as effective as traditional sedatives for producing sedation and maintaining a light sedation level. There was no clear evidence in support of dexmedetomidine reducing the risk of delirium (a kind of acute confusion state), as results were consistent with both no effect and appreciable benefit. We had insufficient information to draw conclusions about reducing the risk of coma. Dexmedetomidine doubled the incidence of slow heartbeat, which was the most commonly reported adverse event. Our review provides no evidence that dexmedetomidine changed the overall death rate. The general quality of evidence ranged from very low to low, as most of the studies were at high risk of bias, serious inconsistency and imprecision, or strongly suspected publication bias. |
We did not identify any new trials from the updated search so the results remain unchanged as follows. We included 13 randomised controlled trials (RCTs) with a total of 1551 women. We found no differences for admission to the neonatal intensive care unit when betamimetics were compared with placebo (risk ratio (RR) 1.28, 95% confidence interval (CI) 0.68 to 2.41; two RCTs of terbutaline with 2600 women) or with magnesium (RR 0.80, 95% CI 0.43 to 1.46; one RCT of 137 women). The rate of preterm birth (less than 37 weeks) showed no significant difference in six RCTs, four comparing ritodrine with placebo/no treatment and two comparing terbutaline with placebo/no treatment (RR 1.11, 95% CI 0.91 to 1.35; 644 women). We observed no differences between betamimetics and placebo, no treatment or other tocolytics for perinatal mortality and morbidity outcomes. Some adverse effects such as tachycardia were more frequent in the betamimetics groups than the groups allocated to placebo, no treatment or another type of tocolytic. Available evidence does not support the use of oral betamimetics for maintenance therapy after threatened preterm labour. | Oral betamimetics for maintenance therapy after threatened preterm labour do not prevent preterm labour. This conclusion is based on 13 randomised controlled trials with a total of 1551 women. In this review, the betamimetics ritodrine and terbutaline did not reduce the rate of preterm birth (eight trials), or prevent problems with babies that required admission to the neonatal intensive care unit (two trials), when compared with placebo, no treatment or other tocolytic drugs. Betamimetics may cause pregnant women to have an increased heart rate (palpitations) and rate of breathing, low blood pressure, nausea and vomiting, and high blood sugar concentrations as side effects. |
We included 13 trials involving 514 participants. There was a significant effect of treatment on subjective reports of memory in the short term (standard mean difference (SMD) 0.36, 95% confidence interval (CI) 0.08 to 0.64, P = 0.01, moderate quality of evidence), but not the long term (SMD 0.31, 95% CI -0.02 to 0.64, P = 0.06, low quality of evidence). The SMD for the subjective reports of memory had small to moderate effect sizes. The results do not show any significant effect of memory rehabilitation on performance in objective memory tests, mood, functional abilities, or quality of life. No information was available on adverse events. Participants who received cognitive rehabilitation for memory problems following a stroke reported benefits from the intervention on subjective measures of memory in the short term (i.e. the first assessment point after the intervention, which was a minimum of four weeks). This effect was not, however, observed in the longer term (i.e. the second assessment point after the intervention, which was a minimum of three months). There was, therefore, limited evidence to support or refute the effectiveness of memory rehabilitation. The evidence was limited due to the poor quality of reporting in many studies, lack of consistency in the choice of outcome measures, and small sample sizes. There is a need for more robust, well-designed, adequately powered, and better-reported trials of memory rehabilitation using common standardised outcome measures. | The evidence is current to May 2016. In this review, we included 13 studies with 514 participants. Seven trials were conducted with community participants, four with in-patients, and two with mixed community and in-patient samples. Participants received various types of memory retraining techniques, including training using computer programs and training in the use of memory aids, such as diaries or calendars. In three studies treatment was provided in groups and in 10 studies treatment was provided individually. Treatment lasted between two weeks and 10 weeks. In these studies, those who received the treatment were compared with a control group. The control group included those who did not receive cognitive rehabilitation or received another form of treatment. The control groups varied. Some studies had a control group wherein people received their usual care, whereas in others individuals in the control groups were placed on a waiting list to receive cognitive rehabilitation. We found that people who received cognitive rehabilitation reported fewer memory problems in daily life immediately after treatment compared with the control groups. This represents a small to moderate effect of the intervention in comparison to the control group. However, there was no evidence that the benefits persisted in the long term. We found no evidence that cognitive rehabilitation improved people's independence in activities of daily living, mood, or quality of life. There was no information about any harm caused to participants from taking part in cognitive rehabilitation. The quality of the evidence ranged from very low (effect on outcomes that relate to everyday activities) to moderate (effect on self-reported memory problems, memory tests, and mood measures). There were a number of flaws in these studies, such as having very few people in them, and these could have affected our findings. |
Three trials involving two different interventions were included. Two trials involving 680 children compared flushing CVC with urokinase (with or without heparin) versus heparin alone. Neither of these trials reported on the primary outcome of catheter-related blood stream infection (CRBSI). There was a non-significantly decreased rate of catheter-associated infection (CAI) (Rate Ratio 0.72, 95% confidence interval 0.12 to 4.41) in the urokinase (with or without heparin) arm compared with the heparin arm. One trial involving 113 children compared frequency of catheter dressing change every 15 days versus every 4 days. It did not report on CRBSI or CAI. There were no premature catheter removals for infection in either of the trial arms. Three RCTs for only two types of interventions to prevent CVC-related infections in children with cancer have been identified. Flushing CVC with urokinase (with or without heparin) compared to heparin alone possibly leads to decrease in CAI rates. Changing catheter dressings every 15 days versus every 4 days does not lead to more premature catheter removals due to infection although data were insufficient to assess if catheter-related infection rates were changed. | A total of three research studies were identified. Two studies showed that there may be a decrease in CVC-related blood infections if the space in the CVC was washed and filled at regular intervals with urokinase (a drug which dissolves blood clots) with/without heparin (a drug which prevents the formation of blood clots) compared to heparin alone. One study showed that changing the dressing which covered the skin at the insertion of CVC every 15 days rather than every 4 days did not lead to an increased removal of the CVC because they had become infected. No research studies were identified for several other potential strategies which could reduce CVC-related infections in children with cancer. |
Three randomised controlled trials involving 2270 women from high-income countries were eligible for inclusion in the review. Outcomes were reported for 1280 infants in one study. The interventions assessed in the trials were designed to be used either independently by women or mediated through the involvement of independent support. No studies looked at shared decision supports, that is, interventions designed to facilitate shared decision-making with health professionals during clinical encounters. We found no difference in planned mode of birth: VBAC (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.97 to 1.10; I² = 0%) or caesarean birth (RR 0.96, 95% CI 0.84 to 1.10; I² = 0%). The proportion of women unsure about preference did not change (RR 0.87, 95% CI 0.62 to 1.20; I² = 0%). There was no difference in adverse outcomes reported between intervention and control groups (one trial, 1275 women/1280 babies): permanent (RR 0.66, 95% CI 0.32 to 1.36); severe (RR 1.02, 95% CI 0.77 to 1.36); unclear (0.66, 95% CI 0.27, 1.61). Overall, 64.8% of those indicating preference for VBAC achieved it, while 97.1% of those planning caesarean birth achieved this mode of birth. We found no difference in the proportion of women achieving congruence between preferred and actual mode of birth (RR 1.02, 95% CI 0.96 to 1.07) (three trials, 1921 women). More women had caesarean births (57.3%), including 535 women where it was unplanned (42.6% all caesarean deliveries and 24.4% all births). We found no difference in actual mode of birth between groups, (average RR 0.97, 95% CI 0.89 to 1.06) (three trials, 2190 women). Decisional conflict about preferred mode of birth was lower (less uncertainty) for women with decisional support (standardised mean difference (SMD) -0.25, 95% CI -0.47 to -0.02; two trials, 787 women; I² = 48%). There was also a significant increase in knowledge among women with decision support compared with those in the control group (SMD 0.74, 95% CI 0.46 to 1.03; two trials, 787 women; I² = 65%). However, there was considerable heterogeneity between the two studies contributing to this outcome ( I² = 65%) and attrition was greater than 15 per cent and the evidence for this outcome is considered to be moderate quality only. There was no difference in satisfaction between women with decision support and those without it (SMD 0.06, 95% CI -0.09 to 0.20; two trials, 797 women; I² = 0%). No study assessed decisional regret or whether women's information needs were met. Qualitative data gathered in interviews with women and health professionals provided information about acceptability of the decision support and its feasibility of implementation. While women liked the decision support there was concern among health professionals about their impact on their time and workload. Evidence is limited to independent and mediated decision supports. Research is needed on shared decision support interventions for women considering mode of birth in a pregnancy after a caesarean birth to use with their care providers. | We found three studies (involving 2270 women), all from high-income countries, that were suitable for this review. The studies looked at the effectiveness of decision support tools designed to be used either independently by women or mediated through the involvement of someone not associated with their care support. No studies looked at shared decision support tools that were intended to help with shared decision making with the pregnant women and their health professionals during pregnancy care visits. We found that the use of these decision support tools made no difference to the type of birth women planned, how women actually gave birth, or in the number of women and babies who experienced harm, although only one study reported harms. There was also no difference in the proportion of women who were unsure about what they wanted. Overall, nearly 65% of women who wanted a VBAC achieved it, while almost all women wanting a caesarean birth had one (97%). We found no difference in the proportion of women who achieved their preferred mode of birth. However, women who used decisional support interventions had less uncertainty about their decision than those that did not use them. Research is needed on the effectiveness of decision support interventions designed to be shared between women and the health professionals caring for them in pregnancy after a caesarean birth. |
We included 21 trials involving 4174 participants. Nine trials used a combination of venesection and plasma volume expander. Twelve trials used plasma volume expander alone. The plasma volume expander was plasma alone in one trial, dextran 40 in 12 trials, hydroxyethyl starch (HES) in five trials and albumin in three trials. Two trials tested haemodilution in combination with another therapy. Evaluation was blinded in 14 trials. Five trials probably included some participants with intracerebral haemorrhage. Haemodilution did not significantly reduce deaths within the first four weeks (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.90 to 1.34). Similarly, haemodilution did not influence deaths within three to six months (RR 1.05; 95% CI 0.93 to 1.20), or death and dependency or institutionalisation (RR 0.96; 95% CI 0.85 to 1.07). The results were similar in confounded and unconfounded trials, and in trials of isovolaemic and hypervolaemic haemodilution. No statistically significant benefits were documented for any particular type of haemodiluting agents, but the statistical power to detect effects of HES was weak. Six trials reported venous thromboembolic events. There was a tendency towards reduction in deep venous thrombosis or pulmonary embolism or both at three to six months' follow-up (RR 0.68; 95% CI 0.37 to 1.24). There was no statistically significant increased risk of serious cardiac events among haemodiluted participants. The overall results of this review showed no clear evidence of benefit of haemodilution therapy for acute ischaemic stroke. These results are compatible with no persuasive beneficial evidence of haemodilution therapy for acute ischaemic stroke. This therapy has not been proven to improve survival or functional outcome. | We identified 21 trials involving 4174 adult, male and female participants with presumed acute ischaemic stroke. The evidence is current to February 2014. Many trials followed participants for at least three to six months. Interventions included isovolaemic regimens (replacing a portion of blood volume with fluid) and hypervolaemic regimens (increasing the total volume of blood by adding fluid) using different types of solutions. This review showed that, when all the studies are taken together, there is no clear evidence of benefit from haemodilution. There is also no clear evidence that any particular mode of haemodilution, with or without blood-letting, using various types of haemodiluting agents, etc, is beneficial. There were no significant serious side effects of this treatment. It is concluded that there is no clear scientific support for the use of haemodilution in the routine treatment of people with acute ischaemic stroke. The overall quality of the evidence was moderate as individual trials were of varying quality. There was little variation among trials. |
A total of 131 studies with 10,514 randomised participants are now included. Overall only 8% of these studies were assessed as being at low risk of bias. Ten interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These ten interventions were: aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate. Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent. | Different strategies are used to try and prevent this condition, and the review of trials found that some of these are effective. Two interventions, cryotherapy (ice chips) and keratinocyte growth factor (palifermin®) showed some benefit in preventing mucositis. Sucralfate is effective in reducing the severity of mucositis, and a further seven interventions, aloe vera, amifostine, intravenous glutamine, granulocyte-colony stimulating factor (G-CSF), honey, laser and antibiotic lozenges containing polymixin/tobramycin/amphotericin (PTA) showed weaker evidence of benefit. These were evaluated in patients with different types of cancer, undergoing different types of cancer treatment. Benefits may be restricted to the disease and treatment combinations evaluated. |
Six randomized controlled trials were included (total 162 participants, age range 7 to 53 years). Pimozide was compared with: placebo and haloperidol (two trials), placebo (one trial), haloperidol (one trial), and risperidone (two trials). Methodological quality was rated ‘fair’ for all studies. Studies used different outcome measurement scales for assessing tic severity and adverse effects. Significant clinical heterogeneity made meta-analysis inappropriate. Pimozide was superior to placebo in three studies, though it caused more side effects than placebo in one of these. Pimozide was inferior to haloperidol in one of three studies (the other two showed no significant difference between the drugs), which also showed significantly fewer side effects associated with pimozide. No significant differences between pimozide and risperidone were detected. Pimozide is an effective treatment for tics in Tourette Syndrome, though the number of trials comparing its effect to placebo and other drugs is limited. Trials of longer duration (minimum six months) are needed to investigate the longer-term effects of pimozide compared to atypical neuroleptics. Future trials should use the Yale Global Tic Severity Scale to assess the main outcome measure, and quantify adverse events with the Extrapyramidal Symptoms Rating Scale. | The review authors searched the medical literature for clinical trials that compared pimozide to other drugs, or a dummy drug (placebo), for treating tics in patients with Tourette Syndrome. The trials identified showed that pimozide was more effective at reducing tics than placebo. It was slightly less effective than the drug haloperidol, but showed fewer side effects. There were no important differences between pimozide and risperidone for either reduction of tics or side effects. In future, if trials could be run for longer, it would help the investigation of the nature of side effects caused by these drugs. |
The database search identified 3963 references. Nineteen trials with 1592 participants were included. Psychological intervention studies (eight trials, 1122 participants, duration of therapy three weeks to 12 months, follow-up after treatment zero to six months) showed beneficial effects on short (i.e. end of treatment), medium (i.e. one to six months after treatment) and long-term (i.e. more than six months after treatment) depression severity (range of standardised mean differences (SMD) -1.47 to -0.14; eight trials). However, between-study heterogeneity was substantial and meta-analyses were not conducted. Short-term depression remission rates (OR 2.88; 95% confidence intervals (CI) 1.58 to 5.25; P = 0.0006; 647 participants; four trials) and medium-term depression remission rates (OR 2.49; 95% CI 1.44 to 4.32; P = 0.001; 296 participants; two trials) were increased in psychological interventions compared to usual care. Evidence regarding glycaemic control in psychological intervention trials was heterogeneous and inconclusive. QoL did not improve significantly based on the results of three psychological intervention trials compared to usual care. Healthcare costs and adherence to diabetes and depression medication were examined in only one study and reliable conclusions cannot be drawn. Diabetes complications and death from any cause have not been investigated in the included psychological intervention trials. With regards to the comparison of pharmacological interventions versus placebo (eight trials; 377 participants; duration of intervention three weeks to six months, no follow-up after treatment) there was a moderate beneficial effect of antidepressant medication on short-term depression severity (all studies: SMD -0.61; 95% CI -0.94 to -0.27; P = 0.0004; 306 participants; seven trials; selective serotonin reuptake inhibitors (SSRI): SMD -0.39; 95% CI -0.64 to -0.13; P = 0.003; 241 participants; five trials). Short-term depression remission was increased in antidepressant trials (OR 2.50; 95% CI 1.21 to 5.15; P = 0.01; 136 participants; three trials). Glycaemic control improved in the short term (mean difference (MD) for glycosylated haemoglobin A1c (HbA1c) -0.4%; 95% CI -0.6 to -0.1; P = 0.002; 238 participants; five trials). HRQoL and adherence were investigated in only one trial each showing no statistically significant differences. Medium- and long-term depression and glycaemic control outcomes as well as healthcare costs, diabetes complications and mortality have not been examined in pharmacological intervention trials. The comparison of pharmacological interventions versus other pharmacological interventions (three trials, 93 participants, duration of intervention 12 weeks, no follow-up after treatment) did not result in significant differences between the examined pharmacological agents, except for a significantly ameliorated glycaemic control in fluoxetine-treated patients (MD for HbA1c -1.0%; 95% CI -1.9 to -0.2; 40 participants) compared to citalopram in one trial. Psychological and pharmacological interventions have a moderate and clinically significant effect on depression outcomes in diabetes patients. Glycaemic control improved moderately in pharmacological trials, while the evidence is inconclusive for psychological interventions. Adherence to diabetic treatment regimens, diabetes complications, death from any cause, health economics and QoL have not been investigated sufficiently. Overall, the evidence is sparse and inconclusive due to several low-quality trials with substantial risk of bias and the heterogeneity of examined populations and interventions. | This review examined clinical trials on psychological treatments and antidepressant drugs in depressed patients with diabetes. The objective was to determine the effects of these treatments on depression, blood sugar, adherence to diabetic treatment regimens, diabetes complications, death from any cause, healthcare costs and health-related quality of life. Nineteen trials with 1592 participants were identified as relevant for the review. Eight trials with 1122 participants investigated psychological treatments versus usual care (duration of therapy three weeks to 12 months, follow-up after treatment zero to six months). Eight trials with 377 participants examined antidepressant drugs versus placebo (duration of intervention three weeks to six months, no follow-up after treatment). Three trials with 93 participants compared the effects of two different antidepressant medications (duration of intervention 12 weeks, no follow-up after treatment). In summary, psychological treatments and antidepressant drugs have a moderate, yet positive, effect on depression outcomes in diabetes patients. Antidepressant drugs have a positive effect on blood glucose, whereas effects on blood glucose are inconclusive for psychological treatments. Patient-rated quality of life did not benefit from psychological or antidepressant drug treatments. Healthcare costs, death from any cause and diabetes complications have not been examined sufficiently. Serious or severe adverse effects were either rare (pharmacological treatments) or not reported (psychological treatments). Overall, the evidence is sparse and inconclusive due to several low-quality trials and the large variety regarding trial characteristics. |
We included four trials with a total of 924 women, with a mean age of 33 years. All assessed the role of metabolomic investigation of embryo viability. We found no RCTs that addressed the metabolomic assessment of oocyte quality or endometrial receptivity. We found low-quality evidence of little or no difference between metabolomic and non-metabolomic assessment of embryos for rates of live birth or ongoing pregnancy (OR 1.02, 95% CI 0.77 to 1.35, I² = 0%; four RCTs; N = 924), live birth alone (OR 0.99, 95% CI 0.69 to 1.44, I² = 0%; three RCTs; N = 597), or miscarriage (OR 1.18, 95% CI 0.77 to 1.82; I² = 0%; three RCTs; N = 869). A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for live birth or ongoing pregnancy (OR 0.90, 95% CI 0.66 to 1.25, I² = 0%; two RCTs; N = 744). Our findings suggested that if the rate of live birth or ongoing pregnancy was 36% in the non-metabolomic group, it would be between 32% and 45% with the use of metabolomics. We found low-quality evidence of little or no difference between groups in rates of clinical pregnancy (OR 1.11, 95% CI 0.85 to 1.45; I²= 44%; four trials; N = 924) or multiple pregnancy (OR 1.50, 95% CI 0.70 to 3.19; I² = 0%; two RCTs, N = 180). Rates of cycle cancellation were higher in the metabolomics group (OR 1.78, 95% CI 1.18 to 2.69; I² = 51%; two RCTs; N = 744, low quality evidence). There was very low-quality evidence of little or no difference between groups in rates of ectopic pregnancy rates (OR 3.00, 95% CI 0.12 to 74.07; one RCT; N = 417), and foetal abnormality (no events; one RCT; N = 125). Data were lacking on other adverse effects. A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for clinical pregnancy (OR 1.03, 95% CI 0.76 to 1.38; I² = 40%; two RCTs; N = 744). The overall quality of the evidence ranged from very low to low. Limitations included serious risk of bias (associated with poor reporting of methods, attrition bias, selective reporting, and other biases), imprecision, and inconsistency across trials. According to current trials in women undergoing ART, there is no evidence to show that metabolomic assessment of embryos before implantation has any meaningful effect on rates of live birth, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy or foetal abnormalities. The existing evidence varied from very low to low-quality. Data on other adverse events were sparse, so we could not reach conclusions on these. At the moment, there is no evidence to support or refute the use of this technique for subfertile women undergoing ART. Robust evidence is needed from further RCTs, which study the effects on live birth and miscarriage rates for the metabolomic assessment of embryo viability. Well designed and executed trials are also needed to study the effects on oocyte quality and endometrial receptivity, since none are currently available. | We found four randomised controlled trials, with a total of 924 women, that compared metabolomic profile assessment with morphology assessment of embryos. The women were an average age of 33 years old. All studies were conducted between 2011 and 2013; length of follow-up was not specified in any of them. The evidence is current to 26 Feburary 2018. One study was supported by an unconditional grant from a biotechnology company (Molecular Biometrics Inc.). The very low conditional superiority for the primary outcome and premature termination of the trial were potentially associated with the funder's interest in the results. One study received funding from a national health organisation, but the equipment was provided by Molecular Biometrics Inc., one was self-funded, while the source of funding was not stated in the fourth study. We found low-quality evidence of no meaningful difference between the intervention and control groups in rates of live birth, ongoing pregnancy, miscarriage, or clinical pregnancy, and multiple pregnancy. We found very low-quality evidence of no meaningful difference between the groups for ectopic pregnancy, and low-quality evidence that cancellation rates were higher in the intervention group. Our findings suggest that if the rate of live birth or ongoing pregnancy was 36% in the non-metabolomic group, it would be between 32% and 45% with the use of metabolomics. Data were lacking on other adverse effects. No properly designed studies reported metabolomic assessment of oocyte quality or endometrium receptivity. The overall quality of evidence ranged from low to very low. Limitations included serious risk of bias (associated with poor reporting of methods, attrition bias, selective reporting and other bias), imprecision, and inconsistency across trials. |
Nine completed RCTs met the inclusion criteria, of which four were cluster-randomised. We also identified five ongoing trials. The included studies had a high or unclear risk of bias, and the GRADE ratings of overall quality were low or very low. The length of follow-up varied from one year in four studies, three years in one study, five or six years in two studies, and ten years in two studies. Eight studies recruited participants from the general population, although there were differences in the age ranges targeted. One study recruited family members of cardiac patients (high risk assessment). There were considerable differences between the studies in the interventions received by the intervention and control groups. There was insufficient evidence to stratify by the types of risk assessment approaches. Limited data were available on all-cause mortality (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.93 to 1.03; 3 studies,103,571 participants, I² = 0%; low-quality evidence) and cardiovascular mortality (RR 1.00, 95% CI 0.90 to 1.11; 2 studies, 43,955 participants, I² = 0%), and suggest that screening has no effect on these outcomes. Data were also limited for combined non-fatal endpoints; overall, evidence indicates no difference in total coronary heart disease (RR 1.01, 95% CI 0.95 to 1.07; 4 studies, 5 comparisons, 110,168 participants, I² = 0%; low-quality evidence), non-fatal coronary heart disease (RR 0.98, 95% CI 0.89 to 1.09; 2 studies, 43,955 participants, I² = 39%), total stroke (RR 0.99, 95% CI 0.90 to 1.10; 2 studies, 79,631 participants, I² = 0%, low-quality evidence), and non-fatal stroke (RR 1.17, 95% CI 0.94 to 1.47; 1 study, 20,015 participants). Overall, systematic risk assessment appears to result in lower total cholesterol levels (mean difference (MD) -0.11 mmol/l, 95% CI -0.17 to -0.04, 6 studies, 7 comparisons, 12,591 participants, I² = 57%; very low-quality evidence), lower systolic blood pressure (MD -3.05 mmHg, 95% CI -4.84 to -1.25, 6 studies, 7 comparisons, 12,591 participants, I² = 82%; very low-quality evidence) and lower diastolic blood pressure (MD -1.34 mmHg, 95% CI -1.76 to -0.93, 6 studies, 7 comparisons, 12,591 participants, I² = 0%; low-quality evidence). One study assessed adverse effects and found no difference in psychological distress at five years (1126 participants). The results are limited by the heterogeneity between trials in terms of participants recruited, interventions and duration of follow-up. Limited data suggest that systematic risk assessment for CVD has no statistically significant effects on clinical endpoints. There is limited evidence to suggest that CVD systematic risk assessment may have some favourable effects on cardiovascular risk factors. The completion of the five ongoing trials will add to the evidence base. | We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments), looking at the effects of systematic risk assessment in healthy adults or those at high risk of developing CVD. We did not include people who already had CVD (e.g. heart attacks and strokes), as these are already known to health services and are being treated. The evidence is current to January 2015. Nine trials met our inclusion criteria. Limited data suggest that screening has no effect on deaths (from any cause) or the number of people having a stroke or developing coronary heart disease. Data were also limited for cardiovascular risk factors (blood lipids and blood pressure) where there were some favourable effects with systematic risk assessment, but there were differences between studies and so results are not certain. The evidence was generally of low or very low quality. Included studies were at some risk of bias, with four studies judged at high risk of bias. Bearing this in mind, the results of this review need to be interpreted cautiously. There is currently limited evidence on the effects of systematic risk assessment for the prevention of CVD. We identified five ongoing trials and when the results are available we will incorporate these. |
We included 15 trials involving 17,674 women. We assessed the quality of the trial evidence for all primary outcomes (i.e. regional analgesia (epidural/spinal), caesarean birth, instrumental vaginal birth (forceps/vacuum), spontaneous vaginal birth, intact perineum, preterm birth (less than 37 weeks) and all fetal loss before and after 24 weeks plus neonatal death using the GRADE methodology: all primary outcomes were graded as of high quality. For the primary outcomes, women who had midwife-led continuity models of care were less likely to experience regional analgesia (average risk ratio (RR) 0.85, 95% confidence interval (CI) 0.78 to 0.92; participants = 17,674; studies = 14; high quality), instrumental vaginal birth (average RR 0.90, 95% CI 0.83 to 0.97; participants = 17,501; studies = 13; high quality), preterm birth less than 37 weeks (average RR 0.76, 95% CI 0.64 to 0.91; participants = 13,238; studies = eight; high quality) and less all fetal loss before and after 24 weeks plus neonatal death (average RR 0.84, 95% CI 0.71 to 0.99; participants = 17,561; studies = 13; high quality evidence). Women who had midwife-led continuity models of care were more likely to experience spontaneous vaginal birth (average RR 1.05, 95% CI 1.03 to 1.07; participants = 16,687; studies = 12; high quality). There were no differences between groups for caesarean births or intact perineum. For the secondary outcomes, women who had midwife-led continuity models of care were less likely to experience amniotomy (average RR 0.80, 95% CI 0.66 to 0.98; participants = 3253; studies = four), episiotomy (average RR 0.84, 95% CI 0.77 to 0.92; participants = 17,674; studies = 14) and fetal loss less than 24 weeks and neonatal death (average RR 0.81, 95% CI 0.67 to 0.98; participants = 15,645; studies = 11). Women who had midwife-led continuity models of care were more likely to experience no intrapartum analgesia/anaesthesia (average RR 1.21, 95% CI 1.06 to 1.37; participants = 10,499; studies = seven), have a longer mean length of labour (hours) (mean difference (MD) 0.50, 95% CI 0.27 to 0.74; participants = 3328; studies = three) and more likely to be attended at birth by a known midwife (average RR 7.04, 95% CI 4.48 to 11.08; participants = 6917; studies = seven). There were no differences between groups for fetal loss equal to/after 24 weeks and neonatal death, induction of labour, antenatal hospitalisation, antepartum haemorrhage, augmentation/artificial oxytocin during labour, opiate analgesia, perineal laceration requiring suturing, postpartum haemorrhage, breastfeeding initiation, low birthweight infant, five-minute Apgar score less than or equal to seven, neonatal convulsions, admission of infant to special care or neonatal intensive care unit(s) or in mean length of neonatal hospital stay (days). Due to a lack of consistency in measuring women's satisfaction and assessing the cost of various maternity models, these outcomes were reported narratively. The majority of included studies reported a higher rate of maternal satisfaction in midwife-led continuity models of care. Similarly, there was a trend towards a cost-saving effect for midwife-led continuity care compared to other care models. This review suggests that women who received midwife-led continuity models of care were less likely to experience intervention and more likely to be satisfied with their care with at least comparable adverse outcomes for women or their infants than women who received other models of care. Further research is needed to explore findings of fewer preterm births and fewer fetal deaths less than 24 weeks, and all fetal loss/neonatal death associated with midwife-led continuity models of care. | We identified 15 studies involving 17,674 mothers and babies (search date 25 January 2016). We included women at low risk of complications as well as women at increased risk, but not currently experiencing problems. All the trials involved professionally-qualified midwives and no trial included models of care that offered home birth. We used reliable methods to assess the quality of the evidence and looked at seven key outcomes: preterm birth (birth before 37 weeks of pregnancy); the risk of losing the baby in pregnancy or in the first month after birth; spontaneous vaginal birth (when labour was not induced and birth not assisted by forceps; caesarean birth; instrumental vaginal birth (births using forceps or ventouse); whether the perineum remained intact, and use of regional analgesia (such as epidural). The main benefits were that women who received midwife-led continuity of care were less likely to have an epidural. In addition, fewer women had episiotomies or instrumental births. Women’s chances of a spontaneous vaginal birth were also increased and there was no difference in the number of caesarean births. Women were less likely to experience preterm birth, and they were also at a lower risk of losing their babies. In addition, women were more likely to be cared for in labour by midwives they already knew. The review identified no adverse effects compared with other models. The trials contributed enough high quality evidence for each key outcome to give us reliable results for each one. We can be reasonably confident that future trials would find similar results for these outcomes. Most women should be offered ‘midwife-led continuity of care’. It provides benefits for women and babies and we have identified no adverse effects. However, we cannot assume the same applies to women with existing serious pregnancy or health complications, because these women were not included in the evidence assessed. |
Six randomised controlled trials (overall 876 participants) lasting 6 to 24 months were included. Two studies (overall 312 participants) compared valproate with placebo, four studies (overall 618 participants) valproate with lithium, one study (overall 23 participants) valproate with olanzapine and one study (overall 220 participants) valproate with the combination of valproate plus lithium. In terms of study quality, most studies reported the methods used to generate random sequence; however, only one study reported enough details on allocation concealment. Four of six included studies described their design as “double blind”, but only two trials reported full details about blinding. Valproate was more effective than placebo in preventing study withdrawal due to any mood episode (RR 0.68, 95% CI 0.49 to 0.93; NNTB 8), but no difference in efficacy was found between valproate and lithium (RR 1.02, 95% CI 0.87 to 1.20). Valproate was associated with fewer participants dropping out of treatment for any cause when compared with placebo or lithium (RR 0.82, 95% CI 0.71 to 0.95 and RR 0.87, 95% CI 0.77 to 0.98, respectively). However, combination therapy with lithium plus valproate was more likely to prevent relapse than was monotherapy with valproate (RR 0.78, 95% CI 0.63 to 0.96). Significant differences in adverse event frequencies were found, and lithium was associated with more frequent diarrhoea, polyuria, increased thirst and enuresis, whereas valproate was associated with increased sedation and infection. Limited evidence supports the efficacy of valproate in the long-term treatment of bipolar disorder. Clinicians and patients should consider acceptability and tolerability profile when choosing between lithium and valproate—their combination or other agents—as long-term treatment for bipolar disorder. | We searched, in a wide-ranging way, for all the useful studies (randomised controlled trials, or RCTs) we could find on long-term treatment of people with bipolar disorder using valproate or any other mood stabiliser, or antipsychotic drugs, or placebo. Three of us looked at RCTs to make sure they were fair experiments. We extracted data from the studies, put all of the evidence together and carried out a statistical analysis to look for significant results. We conducted these searches to 11 January 2013 and found six studies, including a total of 876 participants. The quality of the studies in terms of design was not good, which means that the effects of some drugs might have been overestimated. All of the trials taken together suggest that valproate might help to prevent relapse in bipolar disorder, especially depressive episodes. However, because of limited available evidence, conclusions on valproate compared with placebo and lithium (or other active drugs) cannot be made with any reliable degree of confidence. Lithium is an important drug to compare with valproate because lithium is already known to be effective in preventing relapses of bipolar disorder. When we combined the findings of all studies comparing valproate with lithium, the evidence did not favour valproate or lithium in terms of efficacy. People taking valproate over a long time were more likely than patients given lithium to keep taking their allocated medication. Clinicians and patients should consider the side effects of valproate, including alopecia, tremor and weight gain. We also found a study that compared valproate taken alone with valproate combination therapy (two drugs taken at the same time). This study compared people who took lithium only or valproate only with people who took valproate and lithium together. No evidence showed that use of valproate and lithium compared with lithium alone helped to ensure that patients kept taking their allocated medication. |
Forty-five studies, randomising 1863 participants were included in this review. Thirty two studies presented data that could be meta-analysed. Types of exercise training included cardiovascular training, mixed cardiovascular and resistance training, resistance-only training and yoga. Some studies used supervised exercise interventions and others used unsupervised interventions. Exercise intensity was classed as 'high' or 'low', duration of individual exercise sessions ranged from 20 minutes/session to 110 minutes/session, and study duration was from two to 18 months. Seventeen per cent of studies were classed as having an overall low risk of bias, 33% as moderate, and 49% as having a high risk of bias. The results shows that regular exercise significantly improved: 1) physical fitness (aerobic capacity, 24 studies, 847 participants: SMD -0.56, 95% CI -0.70 to -0.42; walking capacity, 7 studies, 191 participants: SMD -0.36, 95% CI-0.65 to -0.06); 2) cardiovascular dimensions (resting diastolic blood pressure, 11 studies, 419 participants: MD 2.32 mm Hg, 95% CI 0.59 to 4.05; resting systolic blood pressure, 9 studies, 347 participants: MD 6.08 mm Hg, 95% CI 2.15 to 10.12; heart rate, 11 studies, 229 participants: MD 6 bpm, 95% CI 10 to 2); 3) some nutritional parameters (albumin, 3 studies, 111 participants: MD -2.28 g/L, 95% CI -4.25 to -0.32; pre-albumin, 3 studies, 111 participants: MD - 44.02 mg/L, 95% CI -71.52 to -16.53; energy intake, 4 studies, 97 participants: SMD -0.47, 95% CI -0.88 to -0.05); and 4) health-related quality of life. Results also showed how exercise should be designed in order to optimise the effect. Other outcomes had insufficient evidence. There is evidence for significant beneficial effects of regular exercise on physical fitness, walking capacity, cardiovascular dimensions (e.g. blood pressure and heart rate), health-related quality of life and some nutritional parameters in adults with CKD. Other outcomes had insufficient evidence due to the lack of data from RCTs. The design of the exercise intervention causes difference in effect size and should be considered when prescribing exercise with the aim of affecting a certain outcome. Future RCTs should focus more on the effects of resistance training interventions or mixed cardiovascular- and resistance training as these exercise types have not been studied as much as cardiovascular exercise. | Forty-five studies, randomising 1863 participants were included in this review. Thirty two studies presented data that could be included in the meta-analyses.This review showed that regular exercise training significantly improved physical fitness, physical functioning (e.g. walking capacity), and health-related quality of life in adults with chronic kidney disease (CKD). Beneficial effects were also seen on other outcome measures, such as blood pressure, but where the level of evidence is somewhat lower due to too few research studies and or small study populations. Beneficial effects were present in both adults with CKD but not yet in need of dialysis treatment, patients with dialysis (haemodialysis and peritoneal dialysis) and kidney transplant recipients. This systematic review and meta-analysis presents evidence-based data to clinicians and patients on which type of exercise regimen (type of exercises, intensity, frequency and duration of exercise) that should be used to optimise the effect size. The results should be implemented by clinicians who should encourage and inform adults with CKD that there is scientific evidence for beneficial effects of regular exercise training, and who should use an adequate exercise intervention in order to achieve the patient’s and the clinician's goal with the regular exercise. |
Four RCTs (262 adult participants) met the inclusion criteria. One study (N = 33) compared an elemental diet to a non-elemental (polymeric) diet. One study (N = 51) compared a half elemental diet to a regular free diet. Another study (N = 95) compared an elemental diet to 6-mercaptopurine (6-MP) or a no treatment control group. One study (N= 83) compared a polymeric diet to mesalamine. Two studies were rated as high risk of bias due to lack of blinding or incomplete outcome data. The other two studies were judged to have an unclear risk of bias. The studies were not pooled due to differences in control interventions and the way outcomes were assessed. The effect of an elemental diet compared to a polymeric diet on remission rates or withdrawal due to adverse events is uncertain. Fifty-eight per cent (11/19) of participants in the elemental diet group relapsed at 12 months compared to 57% (8/14) of participants in the polymeric diet group (RR 1.01, 95% CI 0.56 to 1.84; very low certainty evidence). Thirty-two per cent (6/19) of participants in the elemental diet group were intolerant to the enteral nutritional formula because of taste or smell and were withdrawn from the study in the first 2 weeks compared to zero participants (0/14) in the polymeric diet group (RR 9.75, 95% CI 0.59 to 159.93; low certainty evidence). Anthropometric measures, QoL, adverse events and serious adverse events were not reported as outcomes. The effect of an elemental diet (half of total daily calorie requirements) compared to a normal free diet on relapse rates is uncertain. Thirty-five per cent (9/26) of participants in the elemental diet group relapsed at 12 months compared to 64% (16/25) of participants in the free diet group (RR 0.54, 95% CI 0.30 to 0.99; very low certainty evidence). No adverse events were reported. This study reported no differences in weight change between the two diet groups. Height and QoL were not reported as outcomes. The effect of an elemental diet compared to 6-MP on relapse rates or adverse events is uncertain. Thirty-eight per cent (12/32) of participants in the elemental diet group relapsed at 12 months compared to 23% (7/30) of participants in the 6-MP group (RR 1.61; 95% CI 0.73 to 3.53; very low certainty evidence). Three per cent (1/32) of participants in the elemental diet group had an adverse event compared to 13% (4/30) of participants in the 6-MP group (RR 0.23, 95% CI 0.03 to 1.98; low certainty evidence). Adverse events in the elemental diet group included surgery due to worsening CD. Adverse events in the 6-MP group included liver injury (n = 2), hair loss (n = 1) and surgery due to an abscess (n = 1). No serious adverse events or withdrawals due to adverse events were reported. Weight, height and QoL were not reported as outcomes The effect of a polymeric diet compared to mesalamine on relapse rates and weight is uncertain. Forty-two per cent (18/43) of participants in the polymeric diet group relapsed at 6 months compared to 55% (22/40) of participants in the mesalamine group (RR 0.76; 95% CI 0.49 to 1.19; low certainty evidence). The mean difference in weight gain over the study period was 1.9 kg higher in the polymeric diet group compared to mesalamine (95% CI -4.62 to 8.42; low certainty evidence). Two participants in the polymeric diet group experienced nausea and four had diarrhoea. It is unclear if any participants in the mesalamine group had an adverse event. Height, QoL, serious adverse events and withdrawal due to adverse events were not reported as outcomes. The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn. More research is needed to determine the efficacy and safety of using enteral nutrition as maintenance therapy in CD. Currently, there are four ongoing studies (estimated enrolment of 280 participants). This review will be updated when the results of these studies are available. | Four studies including 262 adult participants with Crohn's disease in remission were included. One study (33 participants) compared an elemental diet to a non-elemental (polymeric) diet. One study (51 participants) compared an elemental diet to a normal diet (no supplements). One study (95 participants) compared an elemental diet to 6-mercaptopurine or a no treatment control group. One study (83 participants) compared a non-elemental polymeric diet to mesalamine. The researchers searched the medical literature extensively up to 27 July 2018. The study comparing an elemental diet to a polymeric diet found no difference in remission rates at 12 months. Six elemental diet participants were not able to tolerate the enteral nutritional formula because of taste or smell and were withdrawn from the study. Participants who received half of their total daily calorie requirements as elemental diet and the remaining half by normal diet had a lower chance of relapse at 12 months compared to participants who received a free diet. No side effects were reported in this study. The study comparing an elemental diet to 6-mercaptopurine did not show any difference in relapse rates at 12 months. There was no difference in side effect rates. The only side effect reported in the elemental diet group was surgery due to worsening Crohn's disease. Side effects in the 6-mercaptopurine group included liver injury in two participants, hair loss in one participant and surgery to treat an abscess in one participant. The study comparing a polymeric diet to mesalamine found no difference in relapse rates at six months. Two participants the polymeric diet group experienced nausea and four had diarrhoea. It is unclear if any participants in the mesalamine group had side effects. No serious side effects were reported in any of the studies. The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the effectiveness and safety of enteral nutrition for maintenance of remission in Crohn's disease can be drawn. More research is needed to determine the effectiveness and safety of using enteral nutrition as maintenance therapy in Crohn's disease. Currently, there are four ongoing studies (estimated enrolment of 280 participants). This review will be updated when the results of these studies are available. |
We included 81 studies (69,094 participants), five of which are new to this update. We judged 22 studies to be at high risk of bias, 53 to be at unclear risk of bias, and six studies to be at low risk of bias. Fifty studies included abstainers, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty-eight studies focused on special populations who were abstinent because of pregnancy (19 studies), hospital admission (six studies), or military service (three studies). Most studies used behavioural interventions that tried to teach people skills to cope with the urge to smoke, or followed up with additional support. Some studies tested extended pharmacotherapy. We focused on results from those studies that randomised abstainers, as these are the best test of relapse prevention interventions. Of the 12 analyses we conducted in abstainers, three pharmacotherapy analyses showed benefits of the intervention: extended varenicline in assisted abstainers (2 studies, n = 1297, risk ratio (RR) 1.23, 95% confidence interval (CI) 1.08 to 1.41, I2 = 82%; moderate-certainty evidence), rimonabant in assisted abstainers (1 study, RR 1.29, 95% CI 1.08 to 1.55), and nicotine replacement therapy (NRT) in unaided abstainers (2 studies, n = 2261, RR 1.24, 95% Cl 1.04 to 1.47, I2 = 56%). The remainder of analyses of pharmacotherapies in abstainers had wide confidence intervals consistent with both no effect and a statistically significant effect in favour of the intervention. These included NRT in hospital inpatients (2 studies, n = 1078, RR 1.23, 95% CI 0.94 to 1.60, I2 = 0%), NRT in assisted abstainers (2 studies, n = 553, RR 1.04, 95% CI 0.77 to 1.40, I2 = 0%; low-certainty evidence), extended bupropion in assisted abstainers (6 studies, n = 1697, RR 1.15, 95% CI 0.98 to 1.35, I2 = 0%; moderate-certainty evidence), and bupropion plus NRT (2 studies, n = 243, RR 1.18, 95% CI 0.75 to 1.87, I2 = 66%; low-certainty evidence). Analyses of behavioural interventions in abstainers did not detect an effect. These included studies in abstinent pregnant and postpartum women at the end of pregnancy (8 studies, n = 1523, RR 1.05, 95% CI 0.99 to 1.11, I2 = 0%) and at postpartum follow-up (15 studies, n = 4606, RR 1.02, 95% CI 0.94 to 1.09, I2 = 3%), studies in hospital inpatients (5 studies, n = 1385, RR 1.10, 95% CI 0.82 to 1.47, I2 = 58%), and studies in assisted abstainers (11 studies, n = 5523, RR 0.98, 95% CI 0.87 to 1.11, I2 = 52%; moderate-certainty evidence) and unaided abstainers (5 studies, n = 3561, RR 1.06, 95% CI 0.96 to 1.16, I2 = 1%) from the general population. Behavioural interventions that teach people to recognise situations that are high risk for relapse along with strategies to cope with them provided no worthwhile benefit in preventing relapse in assisted abstainers, although unexplained statistical heterogeneity means we are only moderately certain of this. In people who have successfully quit smoking using pharmacotherapy, there were mixed results regarding extending pharmacotherapy for longer than is standard. Extended treatment with varenicline helped to prevent relapse; evidence for the effect estimate was of moderate certainty, limited by unexplained statistical heterogeneity. Moderate-certainty evidence, limited by imprecision, did not detect a benefit from extended treatment with bupropion, though confidence intervals mean we could not rule out a clinically important benefit at this stage. Low-certainty evidence, limited by imprecision, did not show a benefit of extended treatment with nicotine replacement therapy in preventing relapse in assisted abstainers. More research is needed in this area, especially as the evidence for extended nicotine replacement therapy in unassisted abstainers did suggest a benefit. | We updated our searches of research databases in May 2019. We found 81 studies that tested various ways of trying to help people who had recently quit smoking not to relapse. Five of them were new for this update. Fifty studies included people who had already quit, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty-eight studies focused on people who needed to stop smoking for a limited period of time because they were pregnant (19 studies), in hospital (six studies), or because of military service (three studies). Most of the studies used behavioural support treatments that tried to teach people skills to cope with the urge to smoke, or followed up with additional leaflets or calls, internet or mobile phone resources, or additional counselling. Some studies tested extending the use of medicines for helping people to quit smoking, in the hope of preventing relapse. The evidence we found does not support the use of behavioural treatments to help prevent relapse after quitting smoking. This result was the same in all of the different groups of people studied. The most promising treatments involved extending treatment with stop-smoking medicine, in particular, varenicline. Extending treatment with bupropion did not appear to help and there was not enough evidence on extending treatment with nicotine replacement therapy. For behavioural treatments, the certainty of the evidence was moderate. This is because of the diversity of results among studies. The certainty of evidence for treatments with quit-smoking medicines varied. There was moderate-certainty evidence for varenicline, moderate-certainty evidence for bupropion, and low-certainty evidence for nicotine replacement therapy (NRT), and for NRT and bupropion together. Certainty in the evidence was limited by small study sizes. |
Two trials (341 eyes of 238 children and adults) were included comparing efficacy and safety of laser photocoagulation to no therapy in people with proliferative sickle retinopathy. There were 121 males and 117 females with an age range from 13 to 67 years. The laser photocoagulation technique used was different in the two trials; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; and the second, two-centre trial, employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre. The follow-up period ranged from a mean of 21 to 32 months in one trial and 42 to 47 months in the second. Both trials were at risk of selection bias (random sequence generation) because of the randomisation method employed for participants with bilateral disease. One study was considered to be at risk of reporting bias. Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported that complete regression of proliferative sickle retinopathy was seen in 30.2% in the laser group and 22.4% in the control group (no difference between groups). The same trial reported the development of new proliferative sickle retinopathy in 34.3% of laser-treated eyes and in 41.3% of eyes given no treatment; again, there was no difference between treatment groups. The second trial, using feeder vessel coagulation, did not present full data for either treatment group for these outcomes. There was evidence from both trials (341 eyes) that laser photocoagulation using scatter laser or feeder vessel coagulation may prevent the loss of vision in eyes with proliferative sickle retinopathy (at median follow up of 21 to 47 months). Data from both trials indicated that laser treatment prevented the occurrence of vitreous haemorrhage with both argon and xenon laser; with the protective effect being greater with feeder vessel laser treatment compared to scatter photocoagulation. Regarding adverse effects, the incidence of retinal tear was minimal, with only one event reported. Combined data from both trials were available for 341 eyes; there was no difference between the laser and control arms for retinal detachment. In relation to choroidal neovascularization, treatment with xenon arc was found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow up of three years or more. Data regarding quality of life and other adverse effects were not reported in the included trials. Our conclusions are based on the data from two trials conducted over 20 years ago. In the absence of further evidence, laser treatment for sickle cell disease-related retinopathy should be considered as a one of therapeutic options for preventing visual loss and vitreous haemorrhage. However, it does not appear to have a significant different effect on other clinical outcomes such as regression of proliferative sickle retinopathy and development of new ones. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). There is limited evidence on safety, overall, scatter argon laser photocoagulation is superior in terms of adverse effects, although feeder vessel coagulation has a better effect in preventing vitreous haemorrhage. Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors. In addition, patient-important outcomes as well as cost-effectiveness should be addressed. | We included two randomised trials with 341 eyes of 238 participants comparing laser treatment to no intervention. There were 121 males and 117 females with an age range from 13 to 67 years. The trials employed different types of laser treatment. One trial employed scatter laser treatment in which lasers were applied to the retina near the new blood vessels using argon laser. Another employed feeder vessel laser coagulation in which lasers were applied directly to feeding blood vessels using xenon arc as well as argon laser. Participants were followed up for an average of 21 to 47 months. There is mixed evidence on the benefits of using laser therapy in people with retinopathy related to sickle cell disease. For instance, the effect of laser therapy on stopping the progression of new blood vessels and the development of new lesions did not differ greatly between the groups. However, there is evidence that laser therapy may prevent loss of vision and sight-threatening complications. Patient-important outcome data, such as quality of life, were not reported. The safety of laser treatment is acceptable, particularly scatter laser treatment using an argon laser. Although xenon arc lasers are associated with a higher number of complications, a loss of vision is not common. However, given that there are few trials with relatively low quality evidence, results should be treated with caution. Further research is needed to examine the safety of laser treatment compared to other interventions. In addition, patient-important outcomes (such as quality of life and loss of driving licence) as well as cost-effectiveness should be addressed. Both trials were at risk of bias due to the way participants were selected for groups (especially since treatment may be required for both eyes). One study was considered to be at risk of reporting bias as some results were only presented for one of the two treatment groups. |
Nine studies of 3449 participants were included. The rate of exchange transfusion was reduced in one study with liberal transfusion criteria (risk ratio (RR) 0.20; 95% confidence interval (CI) 0.13 to 0.31) but not in the other two more recent studies with stringent criteria (typical RR 0.66; 95% CI 0.19 to 2.28). There was no statistically significant difference in the rate of cerebral palsy (typical RR 0.96; 95% CI 0.50 to 1.85; two studies, 756 participants). However, one large study that reported on neurodevelopmental impairment (a composite outcome including cerebral palsy) found a slightly lower rate of neurodevelopmental impairment with prophylactic phototherapy (RR 0.85; 95% CI 0.74 to 0.99; 1804 participants). The prophylactic phototherapy group had lower peak bilirubin levels (mean difference (MD) -2.73; 95% CI -2.89 to -2.57; six studies, 2319 participants) and had fewer neonates with peak unconjugated serum bilirubin levels > 10 mg/dl (typical RR 0.27; 95% CI 0.22 to 0.33; three studies, 1090 participants) or peak unconjugated serum bilirubin levels > 15 mg/dl (typical RR 0.13; 95% CI 0.07 to 0.23; four studies, 1116 participants). There was no statistically significant difference in the rate of all-cause mortality between the two groups (typical RR 1.08; 95% CI 0.93 to 1.26; four studies, 3044 participants). Prophylactic phototherapy helps to maintain a lower serum bilirubin concentration and may have an effect on the rate of exchange transfusion and the risk of neurodevelopmental impairment. However, further well-designed studies are needed to determine the efficacy and safety of prophylactic phototherapy on long-term outcomes including neurodevelopmental outcomes. | In this review we evaluated the efficacy and safety of prophylactic phototherapy in preventing jaundice in preterm or LBW infants. A total of nine clinical trials representing 3449 infants were included. The findings suggest that phototherapy initiated soon after birth (within 36 hours) for preterm or low birth weight infants may prevent the serum bilirubin from reaching a level that would require exchange transfusion and may reduce the risk of impairment of brain and central nervous system development. However, further well-designed studies are needed to evaluate the effects of prophylactic phototherapy on brain and central nervous system development and other long-term outcomes. |
Nine trials (666 participants) evaluated nicotine for postoperative pain. Nicotine may reduce postoperative pain scores at 24 hours by a small amount compared with placebo (eight trials, mean difference -0.88 on a 0 to 10 scale, 95% confidence interval (CI) -1.58 to -0.18; low quality evidence). The effect on pain at one hour and 12 hours postoperatively was less certain (very low quality evidence). Statistical heterogeneity was substantial and not adequately explained by stratification of trials according to type of surgical procedure, smoking status, mode of nicotine administration, timing of administration, or assessed risk of bias. Excluding one trial at high risk of bias resulted in similar findings. The effect of nicotine on postoperative opioid use was uncertain due to small number of participants in the studies. Nicotine probably increases the risk of postoperative nausea (seven trials, RR 1.24, 95% CI 1.03 to 1.50; moderate quality evidence). Three trials assessed sedation but the effect is very uncertain due to the very low quality of evidence. We found no evidence that nicotine increased the risk of vomiting (seven studies, risk difference (RD) 0.03, 95% CI -0.04 to 0.09; low quality evidence). The results from one single small trial were insufficient to establish whether nicotine led to an earlier hospital discharge (very low quality evidence). Based on evidence of generally low quality, nicotine may reduce postoperative pain at 24 hours compared with placebo, but the effects were relatively small (less than 1 point on a 10 point pain scale) and there was substantial heterogeneity in the results of our analyses. Nicotine does not appear to reduce postoperative use of opioids or opioid-related adverse events but probably increases the risk of nausea. More research is needed to determine the effectiveness of nicotine for postoperative pain and to understand the optimal timing, dose, and method of delivery of nicotine. | Major surgery is usually associated with significant pain. The mainstay of treatment for pain following major surgery is opioid medications (strong pain killers such as morphine). However, opioids are not always entirely effective and are associated with side effects including sleepiness (sedation), shallow breathing (respiratory depression), feeling sick (nausea), and being sick (vomiting). Co-administered medications, like paracetamol, may help improve postoperative pain control and reduce the need for opioids. We included nine clinical trials with a total of 666 participants. We searched several databases to March 2014, to find placebo-controlled, randomized trials (clinical studies where people are randomly put into one of two or more treatment groups, one of which includes a pretend (placebo) group) of nicotine for postoperative pain. We also contacted study authors for additional data. Not all studies reported all of the symptoms (outcomes) listed above, so what we can say about some outcomes is limited. We re-ran the search on 28 April 2015. We will assess the one study of interest when we update this review. Our results indicated that there is low quality evidence that nicotine use results in slightly lower postoperative pain scores 24 hours after surgery. At one hour and 12 hours postoperatively the effect was less certain. Nicotine appeared not to reduce use of opioids at 60 minutes or 24 hours, neither was there evidence that it reduced sedation or vomiting. Nicotine was associated with higher risk of nausea than placebo, and this may limit its use. There was not enough data to evaluate the effects of nicotine use on other side effects associated with opioids, including respiratory depression, or the effects of nicotine use on length of hospital stay following surgery. We downgraded the quality of the evidence to low or very low quality largely because of problems with the way that the studies were designed, which could have exaggerated the results, because there was insufficient data in many of the analyses to be certain about the size of the average effect and because the results of some of the studies varied substantially. |
Eleven trials that involved 3435 patients were identified. Of 3435 patients, 52 patients were randomised more than once for different painful bone metastasis sites. Altogether, 3487 painful sites were randomised. The trials included patients with painful bone metastases of any primary sites, but were mainly prostate, breast and lung. The overall pain response rates for single fraction radiotherapy and multifraction radiotherapy were 60% (1059/1779) and 59% (1038/1769) respectively, giving an odds ratio of 1.03 (95% confidence interval [CI], 0.89 to 1.19) indicating no difference between the two radiotherapy schedules. There was also no difference in complete pain response rates for single fraction radiotherapy (34% [497/1441]) and multifraction radiotherapy (32% [463/1435]) with an odds ratio of 1.11 (95% CI 0.94 to 1.30). Patients treated by single fraction radiotherapy had a higher re-treatment rate with 21.5% (267/1240) requiring re-treatment compared to 7.4% (91/1236) of patients in the multifraction radiotherapy arm (odds ratio 3.44 [95% CI 2.67 to 4.43]). The pathological fracture rate was also higher in single fraction radiotherapy arm patients. Three percent (37/1240) of patients treated by single fraction radiotherapy developed pathological fracture compared to 1.6% (20/1236) for those treated by multifraction radiotherapy (odds ratio 1.82 [95% CI 1.06 to 3.11]). The spinal cord compression rates were similar for both arms (odds ratio 1.41 [95% CI 0.72 to 2.75]). Repeated analyses excluding dropout patients gave similar results. Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the retreatment rate and pathological fracture rates were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option. | This review compares whether a single fraction of radiotherapy is better than multifractions of radiotherapy for alleviating the symptoms associated with tumours that have spread to the bone. Eleven randomised trials were identified in the published literature that compared single versus multifraction radiotherapy for bone metastases. Pooled analysis of these trials suggested that single fraction radiotherapy was as effective as multifraction radiotherapy in controlling bone pain. However, there were more bone fractures in patients treated by single fraction radiotherapy, and they received further treatment sessions more often than those receiving multifraction radiotherapy. |
In this update, we found four new studies, for a total of ten studies. We included seven RCTs and three cluster-RCTs involving a total of 4527 participants, although we were unable to pool the data from one cluster-RCT. Three of the ten studies were conducted in low- or middle- income countries. All included studies compared face-to-face interventions with control. Most studies evaluated the effectiveness of a single intervention session delivered to individual parents. The interventions were an even mix of short (ten minutes or less) and longer sessions (15 minutes to several hours). Overall, elements of the study designs put them at moderate to high risk of bias. All studies but one were at low risk of bias for sequence generation (i.e. used a random number sequence). For allocation concealment (i.e. the person randomising participants was unaware of the study group to which participant would be allocated), three were at high risk and one was judged at unclear risk of bias. Due to the educational nature of the intervention, blinding of participants and personnel was not possible in any studies. The risk of bias due to blinding of outcome assessors was judged as low for four studies. Most studies were at unclear risk of bias for incomplete outcome data and selective reporting. Other potential sources of bias included failure to account for clustering in a cluster-RCT and significant unexplained baseline differences between groups. One cluster-RCT was at high risk for selective recruitment of participants. We judged the certainty of the evidence to be low for the outcomes of children's vaccination status, parents' attitudes or beliefs, intention to vaccinate, adverse effects (e.g. anxiety), and immunisation cost, and moderate for parents' knowledge or understanding. All studies had limitations in design. We downgraded the certainty of the evidence where we judged that studies had problems with randomisation or allocation concealment, or when outcomes were self-reported by participants who knew whether they'd received the intervention or not. We also downgraded the certainty for inconsistency (vaccination status), imprecision (intention to vaccinate and adverse effects), and indirectness (attitudes or beliefs, and cost). Low-certainty evidence from seven studies (3004 participants) suggested that face-to-face interventions to inform or educate parents may improve vaccination status (risk ratio (RR) 1.20, 95% confidence interval (CI) 1.04 to 1.37). Moderate-certainty evidence from four studies (657 participants) found that face-to-face interventions probably slightly improved parent knowledge (standardised mean difference (SMD) 0.19, 95% CI 0.00 to 0.38), and low-certainty evidence from two studies (179 participants) suggested they may slightly improve intention to vaccinate (SMD 0.55, 95% CI 0.24 to 0.85). Low-certainty evidence found the interventions may lead to little or no change in parent attitudes or beliefs about vaccination (SMD 0.03, 95% CI -0.20 to 0.27; three studies, 292 participants), or in parents’ anxiety (mean difference (MD) -1.93, 95% CI -7.27 to 3.41; one study, 90 participants). Only one study (365 participants) measured the intervention cost of a case management strategy, reporting that the estimated additional cost per fully immunised child for the intervention was approximately eight times higher than usual care (low-certainty evidence). No included studies reported outcomes associated with parents’ experience of the intervention (e.g. satisfaction). There is low- to moderate-certainty evidence suggesting that face-to-face information or education may improve or slightly improve children's vaccination status, parents' knowledge, and parents' intention to vaccinate. Face-to-face interventions may be more effective in populations where lack of awareness or understanding of vaccination is identified as a barrier (e.g. where people are unaware of new or optional vaccines). The effect of the intervention in a population where concerns about vaccines or vaccine hesitancy is the primary barrier is less clear. Reliable and validated scales for measuring more complex outcomes, such as attitudes or beliefs, are necessary in order to improve comparisons of the effects across studies. | We included trials published up to July 2017. We found ten studies with a total of 4527 participants that looked at the effects of face-to-face information or education for parents. Seven studies were from high-income countries, and three were from low- or middle-income countries. The interventions were a mix of short (under ten minutes) and longer sessions (15 minutes to several hours) that were delivered to new or expectant parents. We analysed data on the effects of face-to-face information or education on seven different outcomes. According to the included studies, face-to-face information or education may have improved children’s vaccination status, probably slightly improved parents’ knowledge or understanding of vaccination, and may slightly have improved parents’ intention to vaccinate. These interventions may have led to little or no difference in parental attitudes or anxiety related to the intervention. Only one study measured the cost of a face-to-face case management strategy. In this study, the cost of fully immunising one additional child was eight times the cost of usual care, but the intervention was complex, and the study was older, and not widely generalisable. No studies measured parents’ satisfaction with the face-to-face intervention. We judged the certainty of the evidence to be moderate for parents' knowledge or understanding, but low for all other outcomes. We downgraded the certainty of the evidence where studies were judged to have problems with bias from different sources (e.g. the way in which participants were assigned to study groups), where there was a lot of variability in results or imprecise estimates, or where we had misgivings about the choice of outcomes measures. This review suggests that immunisation-focused educational messages may be sufficient to improve vaccination coverage and, to a small degree, knowledge, particularly where awareness is identified as a barrier to vaccination. |
Three trials, involving 233 women, are included. There was no evidence of differences in caesarean section rates between the two interventions in the two trials reporting this outcome (risk ratio (RR) 2.04, 95% confidence interval (CI) 0.92 to 4.55). There were no data presented on neonatal or maternal mortality or morbidity. There was no evidence of a difference between castor oil and placebo/no treatment for the rate of instrumental delivery, meconium-stained liquor, or Apgar score less than seven at five minutes. The number of participants was too small to detect all but large differences in outcome. All women who ingested castor oil felt nauseous (RR 59.92, 95% CI 8.46 to 424.52). The three trials included in the review contain small numbers of women. All three studies used single doses of castor oil. The results from these studies should be interpreted with caution due to the risk of bias introduced due to poor methodological quality. Further research is needed to attempt to quantify the efficacy of castor oil as an cervical priming and induction agent. | The review of three trials, involving 233 women, found there has not been enough research done to show the effects of castor oil on ripening the cervix or inducing labour or compare it to other methods of induction. The review found that all women who took castor oil by mouth felt nauseous. More research is needed into the effects of castor oil to induce labour. |
Two randomized controlled trials evaluated the no-scalpel technique and differed in their findings. The larger trial demonstrated less perioperative bleeding (OR 0.49; 95% CI 0.27 to 0.89) and pain during surgery (OR 0.75; 95% CI 0.61 to 0.93), scrotal pain (OR 0.63; 95% 0.50 to 0.80), and incisional infection (OR 0.21; 95% CI 0.06 to 0.78) during follow up than the standard incisional group. Both studies found less hematoma with the no-scalpel technique (OR 0.23; 95% CI 0.15 to 0.36). Operations using the no-scalpel approach were faster and had a quicker resumption of sexual activity. The smaller study did not find these differences; however, the study could have failed to detect differences due to a small sample size as well as a high loss to follow up. Neither trial found differences in vasectomy effectiveness between the two approaches to the vas. The no-scalpel approach to the vas resulted in less bleeding, hematoma, infection, and pain as well as a shorter operation time than the traditional incision technique. No difference in effectiveness was found between the two approaches. | In February 2014, we did a computer search for studies comparing the no-scalpel approach to the vas with the scalpel method. We included randomized controlled trials in any language. For the initial review, we also looked at reference lists of articles and book chapters. We found two trials that looked at the no-scalpel approach to the vas. The trials had somewhat different results. The larger trial showed the no-scalpel method led to less bleeding, infection, and pain during and after the procedure. The no-scalpel approach required less time for the operation and had a faster return to sexual activity. The smaller study did not show these differences. However, the study may have been too small and many men dropped out. The two methods did not differ in the numbers of men who became sterile. |
We included three trials in which a total of 114 infants participated. In one trial, participants were exclusively infants with severe encephalopathy. The other trials also included infants with mild and moderately severe encephalopathy. These studies were generally of good methodological quality, but were too small to exclude clinically important effects of allopurinol on mortality and morbidity. Meta-analysis did not reveal a statistically significant difference in the risk of death (typical risk ratio 0.88; 95% confidence interval (95% CI) 0.56 to 1.38; risk difference -0.04; 95% CI -0.18 to 0.10) or a composite of death or severe neurodevelopmental disability (typical risk ratio 0.78; 95% CI 0.56 to 1.08; risk difference -0.14; 95% CI -0.31 to 0.04). The available data are not sufficient to determine whether allopurinol has clinically important benefits for newborn infants with hypoxic-ischaemic encephalopathy. Much larger trials are needed. Such trials could assess allopurinol as an adjunct to therapeutic hypothermia in infants with moderate and severe encephalopathy and should be designed to exclude important effects on mortality and adverse long-term neurodevelopmental outcomes. | Studies using animal models suggest that allopurinol (a drug commonly used for preventing gout) can reduce the level of brain damage following perinatal asphyxia. Three small randomised controlled trials that examined whether giving allopurinol to newborn infants following perinatal asphyxia affected their outcomes were identified. None of these trials provided any evidence of benefit. Larger trials are needed to exclude important effects on survival and disability. |
We only considered one study eligible for this review (20 participants). Assessments of risk of bias for most domains were unclear or low. Adverse events were only reported in participants from the zonisamide group, making it possible that they were aware of treatment group assignment. We are uncertain as to the effects of zonisamide on motor tasks (mean difference (MD) -0.00, 95% confidence interval (CI) -1.51 to 1.51, very low-quality evidence) and functional disabilities (MD -0.30, 95% CI -1.23 to 0.63, very low-quality evidence) when compared with placebo. Three participants in the zonisamide group (30%) and two participants in the placebo group (20%) discontinued the treatment and withdrew from the study for any reason (very low-quality evidence), however the increased risk of withdrawal in the zonisamide group was statistically non-significant (risk difference (RD) 0.1, 95% CI -0.28 to 0.48). Six participants in the zonisamide group (60%) and none of the participants in the placebo group (0%) developed adverse events (AEs), with a RD of 0.60 (95% CI 0.28 to 0.92; very low quality evidence). The most common AEs, experienced with zonisamide treatment, were headache, nausea, fatigue, sleepiness, and diarrhoea. Quality of life was not assessed in the study included. Based on currently available data, there is insufficient evidence to assess the efficacy and safety of zonisamide treatment for ET. | We found one study comparing zonisamide versus placebo, involving a total of 20 randomised participants with essential tremor. The impact of zonisamide on functional abilities, risk of treatment discontinuation, and adverse events is uncertain because the quality of evidence is very low. Adverse events were only reported in participants from the zonisamide group, making it possible that they were aware of which treatment they had been receiving. Quality of life was not assessed in the study included. The single study we found was small and the possibility of study participants becoming aware of the treatment group means that we cannot be certain about the risk-benefit profile of this treatment. |
We found 21 RCTs including 2482 participants with migraine, and we extracted meta-analytic data from 14 of these studies. The majority of studies recruited participants through advertisements, included participants with migraine according to the International Classification of Headache Disorders (ICHD) criteria and those with and without aura. Most intervention arms were a form of behavioural or cognitive-behavioural therapy. The majority of comparator arms were no treatment, routine care or waiting list. Interventions varied from one 20-minute session to 14 hours of intervention. No study had unequivocally low risk of bias; all had at least one domain at high risk of bias, and 20 had two to five domains at high risk. Reporting of randomisation procedures and allocation concealment were at high or unclear risk of bias. We downgraded the quality of evidence for outcomes to very low, due to very serious limitations in study quality and imprecision. Reporting in trials was poor; we found no preregistrations stipulating the outcomes, or demonstrating equivalent expectations between groups. Few studies reported our outcomes of interest, most only reported outcomes post treatment; follow-up data were sparse. Post-treatment effects We found no evidence of an effect of psychological interventions for migraine frequency in number of migraines or days with migraine (standardised mean difference (SMD) −0.02, 95% confidence interval (CI) −0.17 to 0.13; 4 studies, 681 participants; very low-quality evidence). The responder rate (proportion of participants with migraine frequency reduction of more than 50%) was greater for those who received a psychological intervention compared to control: 101/186 participants (54%) with psychological therapy; 37/152 participants (24%) with control (risk ratio (RR) 2.21, 95% CI 1.63 to 2.98; 4 studies, 338 participants; very low-quality evidence). We found no effect of psychological therapies on migraine intensity (SMD −0.13, 95% CI −0.28 to 0.02; 4 studies, 685 participants). There were no data for migraine duration (hours of migraine per day). There was no effect on migraine medication usage (SMD −0.06, 95% CI −0.35 to 0.24; 2 studies, 483 participants), mood (mean difference (MD) 0.08, 95% CI −0.33 to 0.49; 4 studies, 432 participants), quality of life (SMD −0.02, 95% CI −0.30 to 0.26; 4 studies, 565 participants), or migraine-related disability (SMD −0.67, 95% CI −1.34 to 0.00; 6 studies, 952 participants). The proportion of participants reporting adverse events did not differ between those receiving psychological treatment (9/107; 8%) and control (30/101; 30%) (RR 0.16, 95% CI 0.00 to 7.85; 2 studies, 208 participants). Only two studies reported adverse events and so we were unable to draw any conclusions. We rated evidence from all studies as very low quality. Follow-up Only four studies reported any follow-up data. Follow-ups ranged from four months following intervention to 11 months following intervention. There was no evidence of an effect on any outcomes at follow-up (very low-quality evidence). This review identified 21 studies of psychological interventions for the management of migraine. We did not find evidence that psychological interventions affected migraine frequency, a result based on four studies of primarily brief treatments. Those who received psychological interventions were twice as likely to be classified as responders in the short term, but this was based on very low-quality evidence and there was no evidence of an effect of psychological intervention compared to control at follow-up. There was no evidence of an effect of psychological interventions on medication usage, mood, migraine-related disability or quality of life. There was no evidence of an effect of psychological interventions on migraine frequency in the short-term or long-term. In terms of adverse events, we were unable to draw conclusions as there was insufficient evidence. High and unclear risk of bias in study design and reporting, small numbers of participants, performance and detection bias meant that we rated all evidence as very low quality. Therefore, we conclude that there is an absence of high-quality evidence to determine whether psychological interventions are effective in managing migraine in adults and we are uncertain whether there is any difference between psychological therapies and controls. | We searched databases in July 2018 and found 21 studies with 2482 participants. Most studies investigated one of three interventions, namely a form of psychological therapy called cognitive-behaviour therapy (CBT), which teaches skills to change thoughts and behaviours. Skills include coping strategies, or biofeedback or relaxation, which teaches people to reduce their tension either by concentrating on relaxing exercises or through a machine that gives feedback about muscle tension or body temperature. The remaining psychological treatments were examined in single studies; they included writing about emotions and eye movement desensitisation, and reprocessing, which uses eye movements to help people accept their pain and other negative experiences. We were interested in outcomes following treatment and at the longest available follow-up. We found no evidence that psychological treatments resulted in less migraine frequency in the four weeks following treatment. However, we could only include four studies in this analysis that were not high quality. Four studies reported the proportion of people whose migraines reduced in frequency by 50% or more, and in those studies, people who received psychological treatment were twice as likely to respond to treatment (i.e. 50% reduction in migraine frequency) as those in the control group. There was no evidence that psychological treatments affected migraine intensity, medication use for migraine, mood or quality of life. Only two studies assessed adverse events, and so we were unable to draw conclusions. We found very few follow-up data, and no evidence to support or refute any long-term effects of psychological treatment. We rated the quality of the evidence using four levels: very low, low, moderate, or high. High-quality evidence means that we are very confident in the results. Very low-quality evidence means that we are very uncertain about the results. We judged the quality of evidence as very low. There is no evidence that psychological treatments affect the frequency of migraine. More responders (i.e. those reporting a 50% reduction) received psychological treatment than control, but this was based on very low-quality evidence and therefore we are uncertain of this result. In terms of adverse events, we were unable to draw conclusions as there was insufficient evidence. There were very few long-term data available, and no indication that psychological interventions had any long-term effects. Overall there was an absence of high-quality evidence for the effect of psychological treatment on migraines and therefore we are uncertain whether there is any difference between psychological therapies and controls. Funding of high-quality studies is needed and additional studies may change the conclusions of this review. |
We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study (1 RCT, n=110, RR 1.37, CI 0.84 to 2.24, low-quality evidence). Although there were some data for the outcomes listed above, there were no data on most of the binary outcomes and none on service outcomes (use of hospital/police), satisfaction with treatment, acceptance of treatment, quality of life or economics. Only one study could be included and most data were heavily skewed, almost impossible to interpret and oflow quality. There were also some limitations in the study design with unclear description of allocation concealment and high risk of bias for selective reporting, so no firm conclusions can be made. This review shows how trials in this group of people are possible - albeit difficult. Further relevant trials are needed to evaluate use of haloperidol in treatment of long-term/persistent aggression in people living with psychosis. | The Cochrane Schizophrenia Group ran an electronic search for clinical trials involving the use of haloperidol for psychosis-induced aggression in July 2011 and April 2015. We found one study with 110 participants, diagnosed with schizophrenia or schizoaffective disorder. Participants had been physically aggressive during recent hospitalisation and involved in at least one other aggressive event. The study randomised participants to receive either haloperidol, clozapine or olanzapine. Most data presented were impossible to use and it is unclear if haloperidol is effective for reducing aggression or improving mental state for people who are aggressive due to psychosis. There were no data regarding side effects. The number of people leaving the study early from each treatment group was similar. The quality of evidence available is low, only one study with a high risk of selective reporting of results provided data. No firm conclusions can be made until further good-quality data are available. |
Nine trials were included in the review. Seven trials, comparing antibiotics to placebo or no treatment, were meta-analysed. Systematic bias in design or publication is suggested by trial results. The randomisation results suggest that the probability that true randomisation took place in all trials is very small and the report of most trials regarding design was poor. The proportion of participants with spontaneous bacterial peritonitis varied between the trials from 15% to 50%. The calculated relative risks (95% confidence interval) of spontaneous bacterial peritonitis and mortality among patients treated with antibiotics compared with no treatment/placebo were 0.20 (0.11 to 0.37) and 0.61 (0.43 to 0.87). There were very few reports of adverse events. The pooled estimates suggest that antibiotic prophylaxis might be prudent among cirrhotic patients with ascites and no gastrointestinal bleeding. However, poor trial methodology and report coupled with findings suggesting systematic bias in publication and design reflect the fragility of these findings. Potential hazard to society and the patients themselves from resistant pathogens should be considered when promoting long-lasting antibiotic prophylaxis. It seems that recommending antibiotic prophylaxis is still far from being a substantiated prevention strategy. Trials of better design, well reported, and of longer follow-up are greatly needed. | This systematic review of randomised clinical trials assesses whether antibiotic prophylaxis prevents spontaneous bacterial peritonitis and mortality among cirrhotic patients with ascites (excess fluid in the abdominal cavity) and no gastrointestinal bleeding. Nine trials are included in the review. The pooled rates of spontaneous bacterial peritonitis and mortality indicate that antibiotic prophylaxis reduces both. There are very few reports of adverse events. Reviewing these trials, we found poor methodology, evidence suggesting publication bias, and limited follow-up periods. Thus, the recommendation to prescribe prophylactic antibiotics to cirrhotic patients without gastrointestinal bleeding is hampered by quality of the trials that generated the data. Due to potential hazards, both to society as a whole and the patients, as individuals, before antibiotic prophylaxis can be confidently recommended, trials of better design, well reported, and of longer follow-up are required. |
We included two large trials. One trial compared three-weekly PLD and carboplatin (PLD/carbo) with PAC/carbo. The other trial included four experimental arms, one of which was PLD plus PAC/carbo, that were compared with the standard PAC/carbo regimen. We did not combine results of these two trials in the meta-analysis. We considered the two studies to be at low risk of bias. For the comparison PLD/carbo versus PAC/carbo (820 women; stages Ic to IV), no statistically significant differences in progression-free survival (PFS) (hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.85 to 1.19) or overall survival (OS) (HR 0.94, 95% CI 0.78 to 1.13) were noted between study arms. Severe anaemia (risk ratio [RR] 2.74, 95% CI 1.54 to 4.88) and thrombocytopenia (RR 8.09, 95% CI 3.93 to 16.67) were significantly more common with PLD/carbo, whereas alopecia (RR 0.09, 95% CI 0.06 to 0.14) and severe neurotoxicity (RR 0.09, 95% CI 0.01 to 0.66) were significantly more common with PAC/carbo. Quality of life scores were not significantly different. For the comparison PLD/PAC/carbo versus PAC/carbo (1726 women; stage III/IV), it is important to note that PLD was given for alternate cycles only (i.e. every 6 weeks). No statistically significant difference in PFS (HR 0.98, 95% CI 0.88 to 1.09) or OS (HR 0.95, 95% CI 0.84 to 1.08) between these two treatment arms was reported. However, women in the triplet arm experienced significantly more severe haematological adverse events (anaemia, thrombocytopenia, neutropenia and febrile neutropenia) compared with those given standard treatment. No RCTs evaluated single-agent PLD for first-line treatment of EOC. PLD/carbo is a reasonable alternative to PAC/carbo for the first-line treatment of EOC. Although three-weekly PLD/carbo may be associated with increased dose delays and discontinuations compared with the standard PAC/carbo regimen, it might be more acceptable to women who wish to avoid alopecia or those at high risk of neurotoxicity. No survival benefits appear to be associated with the alternating triplet regimen, and the additional toxicity associated with adding PLD to PAC/carbo limits further investigation. Further studies are needed to establish the safest, most effective PLD/carbo regimen for newly diagnosed disease. | One study compared PLD plus carbo given to women every three weeks versus the standard treatment (paclitaxel (PAC)/carbo every three weeks), and the other added PLD to the standard treatment and compared it with standard treatment only (the latter study also included other treatments not relevant to this review). These studies spanned three years and included 820 and 4100 women, respectively. Most women in these studies had advanced cancer and had undergone surgery to remove as much of the cancer as possible. Key findings Women receiving the PLD/carbo treatment and those given the standard treatment survived for a similar period, but PLD/carbo caused more women to experience low blood counts (anaemia and low platelets) that often led to a delay in treatment or the need to stop treatment. However, PLD/carbo caused far fewer women to experience hair loss and neuropathy (nerve damage causing symptoms such as tingling, numbness, pain, loss of sensation and/or coordination), and so it might help women who find these side effects unacceptable or intolerable. We concluded that three-weekly PLD/carbo is a reasonable alternative to standard platinum-based treatment for newly diagnosed EOC, but more research is needed to establish the safest and most effective dosage and dose frequency. Adding PLD to standard treatment (PAC/carbo) every six weeks did not help women with newly diagnosed ovarian cancer survive longer and was associated with worse effects on blood counts that increased the chance of infection; therefore this triple drug treatment cannot be recommended. Quality of the evidence We considered the evidence related to survival of women after they are treated with PLD/carbo or PAC/carbo, and the evidence related to adverse drug effects to be of high quality. |
We included two trials in this review, with 62 participants included in the analyses. Both trials were conducted in university dental schools in the USA and compared the effects of oral penicillin V potassium (penicillin VK) versus a matched placebo when provided in conjunction with a surgical intervention (total or partial pulpectomy) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth. The patients included in these trials had no signs of spreading infection or systemic involvement (fever, malaise). We assessed one study as having a high risk of bias and the other study as having unclear risk of bias. The primary outcome variables reported in both studies were participant-reported pain and swelling (one trial also reported participant-reported percussion pain). One study reported the type and number of analgesics taken by participants. One study recorded the incidence of postoperative endodontic flare-ups (people who returned with symptoms that necessitated further treatment). Adverse effects, as reported in one study, were diarrhoea (one participant, placebo group) and fatigue and reduced energy postoperatively (one participant, antibiotic group). Neither study reported quality of life measurements. Objective 1: systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscess Two studies provided data for the comparison between systemic antibiotics (penicillin VK) and a matched placebo for adults with acute apical abscess or a symptomatic necrotic tooth when provided in conjunction with a surgical intervention. Participants in one study all underwent a total pulpectomy of the affected tooth, while participants in the other study had their tooth treated by either partial or total pulpectomy. Participants in both trials received oral analgesics. There were no statistically significant differences in participant-reported measures of pain or swelling at any of the time points assessed within the review. The MD for pain (short ordinal numerical scale 0 to 3) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours; and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The SMD for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours; and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The body of evidence was assessed as at very low quality. Objective 2: systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscess We found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults. There is very low-quality evidence that is insufficient to determine the effects of systemic antibiotics on adults with symptomatic apical periodontitis or acute apical abscess. | The evidence on which this review is based was up-to-date as of 26 February 2018. We searched scientific databases and found two trials, with 62 participants included in the analysis. Both trials were conducted at dental schools in the USA and evaluated the use of oral antibiotics in the reduction of pain and swelling reported by adults after having the first stage of root canal treatment under local anaesthetic. The antibiotic used in both trials was penicillin VK and all participants also received painkillers. Key results The two studies included in the review reported that there were no clear differences in the pain or swelling reported by participants who received oral antibiotics compared with a placebo (a dummy treatment) when provided alongside the first stage of root canal treatment and painkillers. However, the studies were small and produced poor quality evidence, and therefore we cannot be certain if the results are correct. Neither study examined the effect of antibiotics on their own, without surgical dental treatment. One trial reported side effects among participants: one person who received the placebo medication had diarrhoea and one person who received antibiotics experienced tiredness and reduced energy after their treatment. Quality of evidence We judged the quality of evidence to be very low. There is currently insufficient evidence to be able to determine the effects of antibiotics in these conditions. |
A single study enrolling 68 non-intubated children was found eligible for inclusion in review. The study had low or unclear risk of bias. It demonstrated no significant difference in respiratory rate, oxygen saturation, hospital admission rate (odds ratio (OR) 0.77; 95% confidence interval (CI) 0.23 to 2.58) and need for mechanical ventilation between ketamine (0.2 mg/kg intravenous bolus over one to two minutes, followed by a 0.5 mg/kg per hour continuous infusion for two hours) and placebo group. There were no significant side effects of ketamine in the study. There was also no difference in need for other adjuvant therapy (OR 2.19; 95% CI 0.19 to 25.40) and in Pulmonary Index Score (mean difference (MD) -0.40; 95% CI -1.21 to 0.41) between the groups. The single study on non-intubated children with severe acute asthma did not show significant benefit and does not support the case studies and observational reports showing benefits of ketamine in both non-ventilated and ventilated children. There were no significant side effects of ketamine. We could not find any trials on ventilated children. To prove that ketamine is an effective treatment for acute asthma in children, there is need for sufficiently powered randomised trials of high methodological quality with objective outcome measures of clinical importance. Future trials should also explore different doses of ketamine and its role in children needing ventilation because of severe acute asthma. | We found, through systematic search, only one study where investigators assessed the usefulness of ketamine for management of severe acute asthma in children. While this single study suggested that there is a lack of evidence for usefulness of ketamine in acute exacerbation of asthma in children, more trials are needed regarding the use of ketamine in acute asthma before more specific recommendations can be made. |
Sixteen studies were eligible for inclusion (n = 1811 participants), 12 (n = 1366 participants) of which were suitable for meta-analysis. No significant heterogeneity was detected. There were no significant differences between depot GnRHa and daily GnRHa in live birth/ongoing pregnancy rates (OR 0.95, 95% CI 0.70 to 1.31, seven studies, 873 women), but substantial differences could not be ruled out. Thus for a woman with a 24% chance of achieving a live birth or ongoing pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 18% and 29%. There was no significant difference between the groups in clinical pregnancy rate (OR 0.96, 95% CI 0.75 to 1.23, 11 studies, 1259 women). For a woman with a 30% chance of achieving clinical pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 25% and 35%. There was no significant difference between the groups in the rate of severe OHSS (OR 0.84, 95% CI 0.29 to 2.42, five studies, 570 women), but substantial differences could not be ruled out. For a woman with a 3% chance of severe OHSS using daily GnRHa injections, the corresponding risk using GnRHa depot would be between 1% and 6%. Compared to women using daily GnRHa, those on depot administration required significantly more gonadotrophin units for ovarian stimulation (standardised mean difference (SMD) 0.26, 95% CI 0.08 to 0.43, 11 studies, 1143 women) and a significantly longer duration of gonadotrophin use (mean difference (MD) 0.65, 95% CI 0.46 to 0.84, 10 studies, 1033 women). Study quality was unclear due to poor reporting. Only four studies reported live births as an outcome and only five described adequate methods for concealment of allocation. We found no evidence of a significant difference between depot and daily GnRHa use for pituitary down regulation in IVF cycles using the long protocol, but substantial differences could not be ruled out. Since depot GnRHa requires more gonadotrophins and a longer duration of use, it may increase the overall costs of IVF treatment. | The review of 16 randomised controlled trials found no evidence that depot versus daily GnRHa injections produce different rates of live birth/ongoing pregnancy, clinical pregnancy or ovarian hyperstimulation syndrome (OHSS). However, substantial differences could not be ruled out. For example, for a woman with a 25% chance of achieving a live birth or ongoing pregnancy using GnRHa depot, the corresponding chance using daily injection would be between 16% and 30%. For a woman with a 25% risk of severe OHSS using GnRHa depot, the corresponding risk using daily injection would be between 4% and 89%. For a woman with a 25% chance of achieving a live birth or ongoing pregnancy using daily GnRHa injections, the corresponding chance using a depot injection would be between 19% and 30% . For a woman with a 25 % chance of severe OHSS using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 9 % and 45 % . Depot GnRHa may increase the cost of an IVF cycle, because it lengthens the period to ovulation and requires the use of higher doses of other hormone drugs. The quality of the studies was unclear due to poor reporting, and only four studies reported live births. |
31 papers reporting the results of 26 trials were included in the review. For studies that compared a step down approach to a constant moderate/low ICS dose, there were no significant differences in lung function, symptoms, rescue medications or asthma control between the two treatment approaches. Significant but clinically small improvements in percent predicted FEV1 ( WMD 5.32, 95% CI 0.65 to 9.99) and non significant improvements in the change in morning PEF were found for high dose ICS compared to moderate dose ICS. There were no significant differences in efficacy between high and low dose ICS. For moderate dose ICS, compared to low dose ICS, there were significant improvements in the change in morning PEF L/min from baseline (WMD 11.14, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD -0.29, 95% CI -0.53 to -0.06 ) . Commencing ICS at double or quadruple a base moderate or low dose had no greater effect than commencing with the base dose. Several studies reported greater improvement in airway hyperresponsiveness for high dose ICS. For patients with asthma who require ICS, commencing with a moderate dose ICS is equivalent to commencing with a high dose ICS and down-titrating. The small significant benefits of commencing with a high ICS dose are not of sufficient clinical benefit to warrant its use when compared to moderate or low dose ICS. Initial moderate ICS dose appears to be more effective than initial low ICS dose. High dose ICS may be more effective than moderate or low dose ICS for airway hyperresponsiveness. There is no benefit in doubling or quadrupling ICS in subjects with stable asthma. | This review compared initial ICS doses for asthma . The results showed that commencing with a moderate dose ICS is as effective as commencing with a high dose ICS and then reducing the dose whilst monitoring symptoms. These results also show that initial moderate dose ICS maybe more effective than initial low dose ICS. No extra benefit was gained by doubling or quadrupling the starting ICS dose. People with asthma should start their treatment with low to moderate doses of ICS. |
In this update, we did not identify any new RCT studies for inclusion. We identified two RCT studies as ongoing that we are likely to include in future updates. Accordingly, our results are unchanged and include three RCTs with a total of 316 participants. All three studies compared the effectiveness of VM in reverting SVT with that of other vagal manoeuvres in a cross-over design. Two studies induced SVT within a controlled laboratory environment. Participants had ceased all medications prior to engaging in these studies. The third study reported on people presenting to a hospital emergency department with an episode of SVT. These participants were not controlled for medications or other factors prior to intervention. The two laboratory studies demonstrated reversion rates of 45.9% and 54.3%, whilst the clinical study demonstrated reversion success of 19.4%. This discrepancy may be due to methodological differences between studies, the effect of induced SVT versus spontaneous episodic SVT, and participant factors such as medications and comorbidities. We were unable to assess any of these factors, or adverse effects, further, since they were either not described in enough detail or not reported at all. Statistical pooling was not possible due to heterogeneity between the included studies. We did not find sufficient evidence to support or refute the effectiveness of VM for termination of SVT. Further research is needed, and this research should include a standardised approach to performance technique and methodology. | Three studies involving a total of 316 participants were included in this review. Analysis of the results showed that reversion success lies somewhere between 19.4% and 54.3%. We could not calculate the likelihood and severity of side effects (adverse events) as the studies provided insufficient information to perform this analysis. Potential side effects have been reported in other articles on the subject; these have included hypotension (sudden lowering of blood pressure) or syncope (brief loss of consciousness). No side effects were reported in the three studies reviewed here. In the three studies, reversion was achieved on completion of each VM. Overall, the VM appears to be a simple, non-invasive method of stopping abnormal heart rhythm, but its safety and overall effectiveness are difficult to quantify. Further research is required to improve the evidence surrounding this practice. |
Twenty two randomised controlled trials were included. Five studies analysed the use of a GnRH agonist versus control. No significant benefit was demonstrated when using GnRH agonists. No evidence of statistically significant benefit was found for one GnRH agonist over another, or vaginal over intramuscular progesterone administration. No difference in pregnancy rate was demonstrated when no treatment was compared to aspirin, steroids, ovarian stimulation, or human chorionic gonadotropin (hCG) prior to embryo transfer, although using hCG several times before the oocyte retrieval decreases the pregnancy rate. Finally, when oocyte recipients were studied further, starting progesterone on the day of oocyte pick-up (OPU) or the day after OPU produced a significantly higher pregnancy rate (OR 1.87, 95% CI 1.13 to 3.08) than when recipients started progesterone the day prior to OPU. There is insufficient evidence to recommend any one particular protocol for endometrial preparation over another with regard to pregnancy rates after embryo transfers. These were either frozen embryos or embryos derived from donor oocytes. However, there is evidence of a lower pregnancy rate and a higher cycle cancellation rate when the progesterone supplementation is commenced prior to oocyte retrieval in oocyte donation cycles. Adequately powered studies are needed to evaluate each treatment more accurately. | A total of 22 randomised controlled trials were included in this review. There is insufficient evidence from these trials to be able to identify one particular intervention for endometrial preparation that clearly improves the treatment outcome for women receiving embryo transfers with either frozen embryos or embryos derived from donated oocytes. Better quality studies are needed to more accurately evaluate each treatment. |
We included eight trials with a total of 5762 participants. The data showed that anticoagulants (in any intensity) are not more efficacious in the prevention of recurrent ischaemic stroke than antiplatelet therapy (medium intensity anticoagulation: relative risk (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.14; high intensity anticoagulation: RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents: RR 1.27 (95% CI 0.79 to 2.03). However, it was clear that medium and high intensity anticoagulation with vitamin K antagonists, with an INR of 2.0 to 4.5, were not safe because they yielded a higher risk of major bleeding complications (medium intensity anticoagulation: RR 1.93, 95% CI 1.27 to 2.94; high intensity anticoagulation: RR 9.0, 95% CI 3.9 to 21). For the secondary prevention of recurrent ischemic stroke after TIA or minor stroke of presumed arterial origin, there is sufficient evidence to conclude that vitamin K antagonists in any dose are not more efficacious than antiplatelet therapy and that medium and high intensity anticoagulation leads to a significant increase in major bleeding complications. | We reviewed eight trials involving 5762 participants that compared anticoagulants with antiplatelet agents for preventing recurrent stroke and found no benefit of low intensity anticoagulation over aspirin, and an increased risk of bleeding with high intensity anticoagulation. |
We included four studies involving 2302 children. One study was at unclear risk of bias and three were at high risk of bias. Included studies reported heterogeneity in both the intervention design and outcome measures used; this made statistical comparison difficult. Additionally this review is limited by poor reporting of intervention procedure and design. Several BCTs were identified in the trials: these included information around the consequences of twice daily brushing and controlling sugar snacking; information on consequences of adverse behaviour and instruction and demonstration regarding skill development of relevant oral health behaviours. Only one included study reported the primary outcome of development of caries. This small study at unclear risk of bias showed a prevented fraction of 0.65 (95% confidence interval (CI) 0.12 to 1.18) in the intervention group. However, as this is based on a single study, this finding should be interpreted with caution. Although no meta-analysis was performed with respect to plaque outcomes (due to differences in plaque reporting between studies), the three studies which reported plaque outcomes all found a statistically significant reduction in plaque in the intervention groups with respect to plaque outcomes. Two of these trials involved an 'active' home component where parents were given tasks relating to the school oral health programme (games and homework) to complete with their children. Secondary outcome measures from one study reported that the intervention had a positive impact upon children's oral health knowledge. Currently, there is insufficient evidence for the efficacy of primary school-based behavioural interventions for reducing caries. There is limited evidence for the effectiveness of these interventions on plaque outcomes and on children's oral health knowledge acquisition. None of the included interventions were reported as being based on or derived from behavioural theory. There is a need for further high quality research to utilise theory in the design and evaluation of interventions for changing oral health related behaviours in children and their parents. | This review examined how successful the interventions in the suitable studies were in improving dental health in children aged from 4 to 12 years. The latest search of relevant studies was carried out on 18th October 2012. Interventions were programmes that enabled children to. ∙ Making lasting changes to toothbrushing habits. ∙ Reduce the amount and how often food and drink known to cause tooth decay were consumed. The trials had to include an educational element which taught skills or gave instructions and one or more accepted techniques to change behaviour. Out of 1518 possible studies found only four were sufficiently relevant and of high enough quality to be included in this review. One small study showed that children who received the behavioural intervention developed fewer caries during the study. Three studies showed that there was less dental plaque (better oral hygiene) in the children in the behavioural intervention groups. More research is needed to confirm these findings. The dental health of 4 to 12 year olds is an important issue - reducing the amount of decay in this group would have a positive impact on overall health, particularly for those living in the poorest communities. More high quality research with well designed programmes will help to establish which techniques are most effective at changing child and parent behaviour to encourage good toothbrushing and discourage sugar snacking. |
We included one randomised clinical trial that compared four groups: electro-coagulation alone, electro-coagulation + dimethyl sulphoxide, electro-coagulation + allopurinol, and control (Salim 1993). The risk of bias in the trial is high. In three groups, patients had their metastases destroyed with diathermy electro-coagulation (current set at No 5) and received: 1) solution of allopurinol by mouth 5 mL 4 x a day or 2) allopurinol by mouth 5 mL (50 mg) 4 x a day or 3) dimethyl sulphoxide by mouth 5 mL (500 mg) 4 x a day. In the control group patients received a solution of allopurinol by mouth 5 mL 4 x a day. The treatment was started in the fifth postoperative day and was continued for five years. Three hundred and six patients who had undergone resection of the sigmoid colon and who had five or more hepatic metastases were included; 75 received electro-coagulation alone (58 were evaluable), 76 received electro-coagulation plus allopurinol (53 were evaluable), 78 received electro-coagulation plus dimethyl sulphoxide (57 were evaluable), and 77 were in the control group (55 evaluable). The authors reported the number of deaths due to disease spread (100% in the control, 98% in electro-coagulation, 87% in electro-coagulation + allopurinol, and 86% in the electro-coagulation + dimethyl sulphoxide groups). There was a significant benefit in favour of the electro-coagulation + allopurinol (risk ratio (RR) 0.87 (95% confidence interval (CI) 0.78 to 0.96)) and electro-coagulation + dimethyl sulphoxide (RR 0.86 (95% CI 0.77 to 0.95)) groups compared to the control group, but no such benefit in the electro-coagulation alone group (RR 0.98 (95% CI 0.95 to 1.02)) compared to the control group. There were no local recurrences, no positive tests for occult blood, and observed pulmonary metastases were always with ultrasonographic evidence of hepatic secondaries and were not significantly different for the experimental groups compared to the control group (electro-coagulation: RR 1.11 (95% CI 0.4 to 3.09)), electro-coagulation + allopurinol (RR 0.86 (95% CI 0.28 to 2.66)), electro-coagulation + dimethyl sulphoxide (RR 0.8 (95% CI 0.26 to 2.48)). None of the adverse events were significantly associated with treatment. On the basis of one randomised trial which did not describe its methodology in sufficient detail to assess risk of bias and quality, excluded 27% of patients after randomisation due to various reasons, and is probably not free from selective outcome reporting bias, there is insufficient evidence to conclude that in patients with colonic cancer liver metastases, electro-coagulation alone brings any significant benefit in terms of survival or recurrence compared with the control. In addition, there is insufficient evidence for the effectiveness of adding allopurinol or dimethyl sulphoxide to electro-coagulation. The probability for selective outcome reporting bias in the trial is high. More randomised trials are needed in order to sufficiently validate electro-coagulation with or without co-interventions. | One randomised clinical trial was included comparing four arms: electro-coagulation alone, electro-coagulation + dimethyl sulphoxide, electro-coagulation + allopurinol and control. The treatment was started in the fifth postoperative day and was continued for five years. Three hundred and six patients were included, but only 223 could be included in the analyses. On the basis of one randomised trial, which did not describe its methodology in sufficient detail to assess risk of bias and quality, excluded 27% of patients after randomisation due to various reasons, and is probably not free from selective outcome reporting bias, there is insufficient evidence to conclude that in patients with colonic cancer liver metastases, electro-coagulation alone brings any significant benefit in terms of survival or recurrence compared with the control group. In addition, there is insufficient evidence for the effectiveness of adding allopurinol or dimethyl sulphoxide to electro-coagulation. |
We found no completed RCT and included 21 observational studies with 71,693 participants. The only eligible RCT is currently ongoing among MSM in China. The pooled effect estimate for HIV acquisition was not statistically significant (20 studies; 65,784 participants; OR 0.86, 95% CI 0.70 to 1.06) and showed significant heterogeneity (I²=53%). In a subgroup analysis, the results were statistically significant in studies of men reporting an insertive role (7 studies, 3465 participants; OR 0.27, 95% CI 0.17 to 0.44; I²=0%) but not in studies of men reporting a receptive role (3 studies, 1792 participants; OR 1.20, 95% CI 0.63 to 2.29; I² = 0%). There was no significant association between male circumcision and syphilis (8 studies; 34,999 participants: OR 0.96, 95% CI 0.82 to 1.13; I² = 0%), herpes simplex virus 1 (2 studies, 2740 participants; OR 0.90, 95% CI 0.53 to 1.52; I²=0%), or herpes simplex virus 2 (5 studies;10,285 participants; OR 0.86, 95% CI 0.62 to 1.21; I²=0%). The overall GRADE quality of evidence was low. None of the included studies assessed adverse effects associated with male circumcision. Current evidence suggests that male circumcision may be protective among MSM who practice primarily insertive anal sex, but the role of male circumcision overall in the prevention of HIV and other sexually transmitted infections among MSM remains to be determined. Therefore, there is not enough evidence to recommend male circumcision for HIV prevention among MSM at present. Further research should be of high quality and further explore interaction with the predominant sexual role. | At present there is no completed randomised controlled trial that has assessed the effects of male circumcision on acquisition of HIV and other sexually transmitted infections among men who have sex with men (MSM). Results from observational studies suggest that circumcision may be protective among MSM who practice primarily insertive anal sex, but the role of male circumcision overall in the prevention of HIV and other sexually transmitted infections among MSM remains to be determined. |
We included 38 studies testing 58 different interventions and containing data on 15519 patients. The studies were conducted in nine countries between 1975 and 2000. The duration of follow-up ranged from two to 60 months. Due to heterogeneity between studies in terms of interventions and the methods used to measure adherence, we did not pool the results. Simplifying dosing regimens increased adherence in seven out of nine studies, with a relative increase in adherence of 8 per cent to 19.6 per cent. Motivational strategies were successful in 10 out of 24 studies with generally small increases in adherence up to a maximum of 23 per cent. Complex interventions involving more than one technique increased adherence in eight out of 18 studies, ranging from 5 per cent to a maximum of 41 per cent. Patient education alone seemed largely unsuccessful. Reducing the number of daily doses appears to be effective in increasing adherence to blood pressure lowering medication and should be tried as a first line strategy, although there is less evidence of an effect on blood pressure reduction. Some motivational strategies and complex interventions appear promising, but we need more evidence on their effect through carefully designed RCTs. | For many interventions it is difficult to draw any real conclusions due to weaknesses of the included studies. However, reducing the number of daily doses appears to be effective in increasing adherence to blood pressure lowering medication and should be tried as a first line strategy although there is little evidence of an effect on blood pressure reduction. Some motivational strategies and complex interventions appear promising but we need more evidence on their effect through carefully designed randomised controlled trials to confirm these findings. |
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